Pseudomonas, Stenotrophomonas, Acinetobacter, and Other Nonfermentative Gram-Negative Bacteria and Medically Important Anaerobic Bacteria in Transplant Recipients - Rolston, Kenneth V. I.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Despite the overall decline in the frequency of documented gram-negative infections in transplant recipients receiving antimicrobial prophylaxis, the proportion of these infections caused by nonfermentative gram-negative bacilli (NFGNB) is increasing. Pseudomonas aeruginosa is the most common species of NFGNB isolated from such patients, from both monomicrobial and polymicrobial infections. The spectrum of infection caused by P. aeruginosa is wide, and involvement of multiple organ systems is not uncommon. Resistance to multiple agents expected to have activity against P. aeruginosa has become a significant problem and, to some extent, has spurred the development of novel antimicrobial agents. Other important NFGNB include Stenotrophomonas maltophilia, Acinetobacter species, and, to a lesser extent, Achromobacter species, Alcaligenes species, nonaeruginosa Pseudomonas species, and Chryseobacterium species. As with P. aeruginosa, resistance to multiple agents is a common thread with these organisms as well. Infections with these organisms are associated with substantial morbidity and mortality. Consequently, in addition to appropriate antimicrobial therapy, infection control and antimicrobial stewardship are important tools in combating the development and spread of infections caused by NFGNB. Anaerobic organisms, on the other hand, are isolated much less frequently, generally from mixed or polymicrobial infections. Although they are frequently co-pathogens in this setting, their importance should not be underestimated.
Keywords: Acinetobacter spp.; Anaerobic bacteria; Antimicrobial stewardship; Infection control; Multiple drug resistance; Nonfermentative gram-negative bacilli; Polymicrobial infection; Pseudomonas spp.; Stem cell transplant; Stenotrophomonas maltophilia

Infections in Transplantation: Introduction and Overview - Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Over the last 70 years, a steady growth in population of patients with severe and mostly iatrogenically induced immune suppression while undergoing myeloablative antineoplastic therapy and blood- and marrow-derived stem cell or solid organ transplantation has resulted in a near-explosive growth of opportunistic infections. Furthermore, the advent and now common use of biologic immunosuppressive drugs are given to an increasing number of patients prior to transplantation or for treatment of complications arising during the posttransplant period such as graft-versus-host disease, lymphoproliferative disorders, opportunistic malignancies, cancer recurrences, and rejection of solid organ allograft. These and other recent therapeutic advances in transplantation procedures continue to be fraught with prolonged and often unpredictable period of drug-induced immune dysregulation. The emergence and spread of difficult-to-treat opportunistic bacterial, viral, fungal, and parasitic diseases in transplant population have evolved under the influence of environmental-, host-, disease-, and treatment-specific variance. A diligent diagnostic adjudication is of utmost importance in a population with known proclivity for atypical disease presentation. Inaccurate diagnosis may result in inappropriate and ineffective empiric therapy that may worsen patients’ morbidity and heighten the risk for further complications and death. Advancement in understanding the immunopathogenesis of infectious diseases, hosts’ immunologic vulnerability for infections, emerging molecular diagnostic paradigms, deciphering potential therapeutic impact of immune modulation by existing and new antimicrobial drugs, and active research and development in mitigation strategies to promote immune recovery and immune preservation are encouraging developments in optimizing care for patients in need for lifesaving transplantation procedures.
Keywords: Advances in infection diagnosis; Blood and marrow hematopoietic stem cells; Cellular immune defects; Humoral immune defects; Microbiome; Microbiota; Neutropenia; Opportunistic infections; Solid organ transplantation; Transplantation

Cytomegalovirus - Safdar, Amar; Armstrong, Donald (Principles and Practice of Transplant Infectious Diseases, 2019)
In the general population, cytomegalovirus (CMV) is a common infection that is frequently acquired at a young age; one in three children in the United States are infected with CMV. In patients undergoing transplantation, CMV most frequently presents as reactivation of a remotely acquired infection, whereas primary CMV infection in seronegative (−) recipients transmitted via allografts harvested from CMV-seropositive (+) donors poses the greatest threat of infection and viral end-organ disease. Naturally acquired CMV infection or infection via unscreened blood and blood products are seldom seen in this population. It is also important to note that in patients undergoing stem cell allograft transplantation, donor CMV (+) status is regarded as a more important prognosticator for complications and unfavorable outcome than transplantation with lesser human leukocyte antigen (HLA-C, HLA-DQ, or HLA-D) mismatch allografts or existence of acute or chronic graft-versus-host disease (GVHD). Similarly, in solid organ allograft recipients, CMV donor/recipient serologic discordance (D+/R−) has been the single most important determinant for post-transplant CMV viremia, CMV disease and survival of the allograft. Compared to other donor prognostic factors such as advance age or blood group type, graft from CMV (−) donor is preferable. HSCT after myeloablative conditioning, major HLA antigen mismatched and/or T cell-depleted grafts, and patients given cord blood stem cells with GVHD have higher susceptibility for CMV infection. Furthermore, CMV infections play an increasingly recognizable role in the incidence of GVHD, risk for invasive fungal disease, recurrence of malignancy, and non-cancer relapse mortality following allograft stem cell transplantation; even in the era of universal antiviral prophylaxis and/or preemptive therapy. Treatment with high-dose antirejection or anti-GVHD therapy with calcineurin inhibitors, corticosteroids, cytotoxic drugs, biologics like anti-CD52, anti-IL2, to a lesser extent, other anti-B cell antibodies that target CD20 and CD19 cell surface antigens are known to deplete hosts’ effective anti-CMV immune surveillance. Strategies to mitigate CMV risk in this population include identifying high-risk cohort prior to transplantation, antiviral drug and immunoprophylaxis for infection prevention, continued effective surveillance for sustained and rising viremia, and institution of preemptive therapy when appropriate. An overview of CMV risk and infection prevention, hosts' immunity -pathogen interaction, spectrum of clinical illness, diagnosis and management of CMV infection with an emphasis on new antiviral drugs, emerging strategies to modify patients' immune-inflammatory response to cytomegalovirus infection, ongoing research in vaccine development, and adaptive cellular immunotherapy are the focus of discussion in this chapter.
Keywords: Abdominal visceral transplant; Allograft rejection; CMV antiviral drugs; CMV pneumonitis; CMV-seronegative recipient; CMV-seropositive donor; Cord blood stem cell transplants; Cytomegalovirus; Encephalitis; Enterocolitis; Face and limb transplant; Graft-versus-host disease; HLA-mismatched transplant; Heart transplant; Kidney transplant; Liver transplant; Lung transplant; Viral hepatitis

Staphylococcus, Streptococcus, and Enterococcus - Safdar, Amar; Armstrong, Donald (Principles and Practice of Transplant Infectious Diseases, 2019)
Gram-positive bacteria (GPB) are an important cause of systemic disease in immunocompromised patients, especially those undergoing transplantation. A rise in infections due to GPB in the last two decades has been attributed to a variety of reasons that prominently include antimicrobial prophylaxis with a focus on prevention of Gram-negative bacterial infections. The near-universal use of indwelling intravascular access devices that are usually retained for an extended duration also contributes toward this trend. In solid organ transplant recipients, postsurgical wound and deep tissue infections resulting from tissue ischemia, prolonged and complicated surgical procedures, allograft rejection, and severity of iatrogenic, drug-induced immune suppression are important factors contributing toward bacterial infections, and GPB are conspicuous among such infections, whereas in stem cell transplant population, presence of mucositis involving the orointestinal tract , severe and prolonged pre-engraftment neutropenia, and graft-versus-host disease involving the skin and orointestinal tract are considered important risk factors for GPB infections. Emergence and widespread distribution of community-acquired methicillin-resistant Staphylococcus aureus has led to the trend for invasive GPB disease among a wide spectrum of population, which also includes transplant recipients. Early diagnosis, prompt institution of appropriate therapy, assessment for outcome prognosticators, and recognizing the potential for early and late infection- and treatment-related complications form the bases for optimum management for such infections. In this chapter, medically important GPB pathogens are discussed, with an emphasis on epidemiology, disease pathogenesis, risk factors, clinical presentation, and management for patients undergoing solid organ and hematopoietic stem cell transplantation.
Keywords: Antibiotic resistance; Enterococcus; Hematopoietic stem cell transplantation; Immune suppression; Pneumococcus; Solid organ transplantation; Staphylococcus aureus; Streptococcus species

Intravascular Catheter and Implantable Device Infections in Transplant Patients - Safdar, Nasia; Abad, Cybele Lara R.; Maki, Dennis G. (Principles and Practice of Transplant Infectious Diseases, 2019)
The use of intravascular devices for administration of drugs, fluids, blood products, and nutritional support is essential in patients undergoing transplantation procedures. These intravascular devices have a significant potential to produce iatrogenic disease, such as bloodstream infection originating from colonization of the indwelling intravascular devices. Over two-thirds of all healthcare-associated bacteremia originate from devices used for vascular access. Patients undergoing hematopoietic stem cell transplantation, who have inherently compromised immune function because of their cancer and are further incapacitated due to the preparatory pretransplant conditioning regimen or graft-versus-host disease, are particularly prone to device-related infections. In this chapter, a comprehensive review of epidemiology, disease pathogenesis, clinical presentation, treatment, and prevention of intravascular device-related infections is presented.
Keywords: Bloodstream infection; Catheter infection; Prevention

Surgical Site Infections: Wound and Stump Infections - Safdar, Nasia; Zerbel, Sara A. M.; Misch, Elizabeth Ann (Principles and Practice of Transplant Infectious Diseases, 2019)
Surgical site infections (SSIs) following transplantation have been linked to increased mortality, graft rejection, increased length of stay, and increased resource utilization ). Rates of SSI vary and can reach as high as 37% for some transplant procedures . The risk of infection depends greatly on type of surgery and patient-specific factors. Postoperative wound infections following transplant generally occur within 30 days of surgery and can range from superficial to organ/space involvement. A number of factors predispose transplant patients to SSI including immunosuppression, reoperation, diabetes, and obesity . The route of infection is dependent on type of transplant surgery and may be both endogenous and exogenous . Microorganisms in posttransplant SSIs are primarily bacterial; however, fungal infections may also play a role . Multidrug-resistant organisms are becoming an increasingly common culprit of SSI in this population due to a heavy exposure to the healthcare system, use of prophylactic antibiotics, and immunosuppression. There are few guidelines to direct therapy. In general, management with debridement alone is not sufficient in the transplant population, due to impaired host defenses. Culture or PCR of tissues is critical to diagnose resistant or unexpected pathogens. Depending upon local epidemiology and site of infection, antibiotics to target resistant Gram-positive and Gram-negative organisms (including Pseudomonas), Candida, and, on occasion, Aspergillus, may be necessary. Measures to prevent SSI during the preoperative, intraoperative, and postoperative period should be evidence-based and incorporated into hospital quality control initiatives.
Keywords: National Healthcare Safety Network; Surgical site infection; Transplant; Treatment; Wound classification

Aspergillosis - Satlin, Michael J.; Jacobs, Samantha E.; Walsh, Thomas J. (Principles and Practice of Transplant Infectious Diseases, 2019)
Aspergillus species are ubiquitous fungi that infect humans after their asexual spores are inhaled and deposited in the respiratory tract. Neutrophils and cell-mediated immunity are crucial components of host defenses that prevent invasion of Aspergillus, and these elements are often lacking or impaired in transplant recipients. Aspergillosis is the most common invasive fungal infection in hematopoietic stem cell transplant recipients and the second most common in solid organ transplant recipients. Invasive pulmonary disease is the most common site of infection, followed by sinusitis. Infection can also disseminate to the central nervous system and virtually any organ system. Use of computed tomography and biomarkers provides additional sensitivity, compared to conventional culture and microscopy-based diagnostic methods. Voriconazole and isavuconazole are treatments of choice for invasive aspergillosis, with isavuconazole having fewer adverse effects and more predictable pharmacokinetics. Adding an echinocandin to voriconazole may provide additional benefit. Prophylaxis against invasive aspergillosis with mold-active antifungal agents is indicated in certain high-risk transplant recipients.
Keywords: Aspergillosis; Clinical manifestations; Diagnosis; Epidemiology; Pathogenesis; Prevention; Transplant; Treatment

Invasive Fungal Disease in the Transplant Population: An Overview - Saullo, Jennifer L.; Perfect, John R.; Alexander, Barbara D. (Principles and Practice of Transplant Infectious Diseases, 2019)
There are numerous fungal pathogens which merit consideration in the hematopoietic cell and solid organ transplant recipients including yeasts, filamentous molds, and endemic fungi. Important differences in the incidence, types, and timeline of infections exist among the differing transplant groups. The overall risk of invasive fungal infection is affected by a multitude of factors including the transplant donor and recipient as well as transplant type. These considerations guide the implementation of prophylactic strategies and assist in targeting those at highest risk of fungal disease.
Keywords: Aspergillus; Candida; Cryptococcus; Endemic Mycoses; Epidemiology; Fungal Infections; Fungal Prophylaxis; Hematopoietic Cell Transplant; Immunocompromised; Mucormycosis; Solid Organ Transplant

Enterovirus Infection in Immunocompromised Hosts - Schaenman, Joanna M. D.; Ho, Dora Y.; Baden, Lindsey R.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
The Enteroviridae are single-stranded RNA viruses in the Picornaviridae family notable for their ability to cause a wide range of diseases, with more severe disease manifestations in the immunocompromised host. Humans are the reservoir for Enteroviridae, and person-to-person transmission occurs via the fecal-oral or respiratory route. Intact innate immune response including NK cells and macrophages plays an important role during the initial phase of infection followed by T- and B-cell adaptive immunity, which is central in effective viral clearance. Enteroviral infections peak in the summer and fall months. Poliovirus classically causes a paralytic poliomyelitis with weakness and paralysis. Other enteroviral diseases include upper respiratory infections, HFMD, herpangina, myositis, myocarditis, aseptic meningitis, encephalitis, as well as a flaccid paralysis similar to poliovirus infection. Patients with B-cell immune defects including agammaglobulinemia are susceptible to chronic enterovirus infections including chronic meningoencephalitis. Patients undergoing HSCT may develop potentially life-threatening gastroenteritis and viral pneumonitis. No antiviral therapy is currently available; IVIG therapy is suggested for patients with enteroviral myocarditis and encephalitis. A comprehensive review of enteroviral illness is presented in the transplant population.
Keywords: Coxsackievirus; Enterovirus; Enterovirus 71; Immunocompromised hosts; Non-poliovirus; Poliovirus

Pharmacokinetics and Pharmacodynamics of Antibiotics in Transplant Patients - Schoeppler, Kelly E.; Mueller, Scott W.; Barber, Gerard R. (Principles and Practice of Transplant Infectious Diseases, 2019)
Transplant infectious diseases are among the most challenging sectors of present-day medicine. Solid organ and hematopoietic stem cell transplants are being performed with increasing frequency, and the threat of infection is ever-present due to a degree of dependence upon potent immunosuppressive agents that ensure sustained engraftment. Accordingly, antibacterial agents will be employed as well. The responses of these patients to bacterial infection can be very different when compared to the immunocompetent host. This lack of intact immune status presents a markedly different patient population and often requires a different approach to the prophylaxis or treatment of infection. Segments of patient populations within transplant medicine, such as cystic fibrosis or elderly patients, pose physiologic challenge to optimizing medication regimens as they also can be taking other medications indicated for chronic underlying conditions that precede or develop following transplantation. Consideration for changes in the pharmacokinetics of antimicrobials is critical in achieving adequate serum concentrations while minimizing toxicity. Clinicians must be mindful of drug interactions of antibacterials to immunosuppressive agents as well as these other medications. Despite the fact that ultimately the dynamics of these drug interactions can be crucial and influence the success or failure of the transplanted organ, methodologically solid pharmacokinetic drug interaction trials are lacking for many commonly used antibacterials. A keen awareness of the pharmacokinetic and pharmacodynamic activities of medications within the transplant recipient is crucial. For example, the anticipated changes of a drug’s concentration or potency with new or sustained exposure to another agent, the relevance of objective measurements of drug concentrations, and the employment of novel routes of administration such as aerosolization to preferentially target pulmonary exposure while minimizing systemic activities must be recognized. There has been considerable interest regarding the influence of several antibacterials on immunomodulation. This chapter will discuss these issues within the context of stewardship and optimization citing the most recent evidence, trends, and controversy. For now, among recipients of solid organ and hematopoietic stem cell transplantation, the drug classes of antimicrobials and immunosuppressives remain inextricably woven.
Keywords: Aerosolized; Area under the concentration curve (AUC); Bioavailability (F); Drug interactions; Immunomodulation; Investigational; Minimum inhibitory concentration (MIC); Therapeutic drug monitoring (TDM); Volume of distribution (Vd)

Pharmacokinetics and Pharmacodynamics of Antiviral Drugs in Special Population - Scipione, Marco R.; Papadopoulos, John (Principles and Practice of Transplant Infectious Diseases, 2019)
Viral infections are a global public health problem and can contribute significantly to patient morbidity and mortality. It is estimated that there are 350 million people worldwide who are infected with hepatitis B virus and 17,000 new cases per year of hepatitis C are identified (Wasley et al., MMWR Morb Mortal Wkly Rep 57(SS-2):1–24, 2008). Herpes viruses are common, with an estimated seroprevalence of 50% for herpes simplex virus type-1 and 20% herpes simplex virus type-2 seroprevalence among adults in the United States (Piret and Boivin, Antimicrob Agents Chemother 55(2):459–472, 2011). Influenza infections worldwide lead to serious morbidity and have been associated with thousands of deaths each year; 18,500 deaths were attributed to 2009 influenza A H1N1 pandemic alone (MMWR Morb Mortal Wkly Rep 59(33):1057–1089, 2010; Dawood et al., Lancet Infect Dis 12(9):687–695, 2012). It is imperative that clinicians have an intimate knowledge of any medication used in their practice and a working knowledgebase of pharmacokinetics and pharmacodynamics is especially true in the discipline of infectious diseases. This chapter provides a detail review of pharmacokinetic and pharmacodynamic parameters of antiviral agents utilized to treat select viral infections in patients undergoing transplantation.
Keywords: Antiviral agents; Hepatitis; Herpes; Influenza; Pharmacodynamics; Pharmacokinetics

Antimicrobial Stewardship: Considerations for a Transplant Center - Seo, Susan K.; Forrest, Graeme N. (Principles and Practice of Transplant Infectious Diseases, 2019)
Caring for immunocompromised patients is challenging. Despite significant advances, infection remains a major cause of morbidity and mortality, and as such, these patients are frequently exposed to antimicrobial agents. Antimicrobial stewardship programs (ASPs) can assist transplant centers in optimizing antibiotic usage, particularly in this age of growing microbial resistance and the scarcity of new anti-infective agents in development. The collaborative approach of antimicrobial stewardship serves well in the transplant center where multidisciplinary teamwork is the norm. The purpose of this chapter is to explore both the basic and unique aspects of coordinating an ASP at a transplant center.
Keywords: Antimicrobial stewardship; Cost savings; Guidelines; Infectious diseases; Microbiology; Multidisciplinary; Pharmacy; Prescribing strategies; Rapid molecular testing

Emerging fungal infections in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice - Shoham, Shmuel; Dominguez, Edward A.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated AST-IDCOP guidelines review the epidemiology, diagnosis, and management of emerging fungi after organ transplantation. Infections due to numerous generally innocuous fungi are increasingly recognized in solid organ transplant (SOT) recipients, comprising about 7%-10% of fungal infections in this setting. Such infections are collectively referred to as emerging fungal infections and include Mucormycetes, Fusarium, Scedosporium, and dematiaceous fungi among others. The causative organisms are diverse in their pathophysiology, uncommon in the clinical setting, have evolving nomenclature, and are often resistant to multiple commonly used antifungal agents. In recent years significant advances have been made in understanding of the epidemiology of these emerging fungal infections, with improved diagnosis and expanded treatment options. Still, treatment guidelines are generally informed by and limited to experience from cohorts of patients with hematological malignancies and/or solid and stem cell transplants. While multicenter randomized controlled trials are not feasible for these uncommon infections in SOT recipients, collaborative prospective studies can be valuable in providing information on the epidemiology, clinical manifestations, treatment strategies, and outcomes associated with the more commonly encountered infections.
Keywords: antifungal therapy; fusarium; scedosporium; zygomyces

Immunomodulatory Properties of Antifungal Agents on Immune Functions of the Host - Simitsopoulou, Maria; Roilides, Emmanuel (Principles and Practice of Transplant Infectious Diseases, 2019)
The first line and the most effective form of antifungal host defense are comprised by phagocytes, particularly neutrophils and monocytes/macrophages that play a central role in local containment of infection and prevent systemic dissemination. These immune cells are also exposed to antifungal drugs while patients undergo systemic antifungal therapy. In the phagocyte-fungus-antifungal drug interplay, drugs including amphotericin B formulations, azoles, and echinocandins may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Drugs, through modulation of fungal virulence, may initiate different immune response pathways in the phagocytes, leading to upregulation of gene expression for a pro-inflammatory response or to antifungal synergism versus antagonism. Additionally, indirect modulation of mononuclear innate immune cell behavior by pretreatment with cytokines and exposure to antifungal agents has shown a promising outcome for combined drug-cytokine therapy in certain difficult to treat life-threatening invasive fungal diseases. In this chapter, the immunomodulatory role of antifungal agents on phagocytic immune cells in response to fungal stimulation is presented. The underlying mechanisms and the potential clinical relevance of such antifungal effects are also discussed.
Keywords: Antifungal agents; Aspergillus; Candida; Immune response; Immunocompromised host; Immunomodulation; Voriconazole

Interactions between anti-infective agents and immunosuppressants—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Sparkes, Tracy; Lemonovich, Tracy L.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation provide an update on potential drug-drug interactions between anti-infectives and immunosuppressants, which are most notable with calcineurin and mTOR inhibitors. Drug-drug interactions may occur through pharmacokinetic mechanisms leading to altered drug concentrations of either the anti-infective or immunosuppressive drug, or by pharmacodynamic interactions increasing or decreasing the efficacy or toxicity of the medications. Many of the significant pharmacokinetic interactions occur through inhibition or induction of the cytochrome 3A4 system by anti-infective agents leading to increased or decreased immunosuppressive agent levels, respectively. The membrane transporter P-glycoprotein is also often involved in drug interactions. Since the last iteration of these guidelines, multiple new hepatitis C virus direct-acting antivirals have become available for use in SOT recipients. Of these agents, some are substrates of cytochrome and drug transporter systems, while others inhibit these systems and may affect immunosuppressive agents. Due to the high risk for drug-drug interactions in the solid organ transplant population, practitioners must be aware of potential interactions and be vigilant in monitoring and adjusting drug dosing when appropriate.
Keywords: Antimicrobials; antifungals; antimicrobials; antiviral; drug interactions; immunosuppressants; organ transplant

Mucormycosis - Spellberg, Brad; Maertens, Johan (Principles and Practice of Transplant Infectious Diseases, 2019)
Mucormycosis (formerly known as zygomycosis) is a life-threatening infection caused by fungi of the order Mucorales. Mucormycosis is an infectious emergency that typically occurs in patients with defects in host defense and/or with increased available serum iron, but can also occur after traumatic implantation of the etiologic fungi through skin. Recent years have witnessed some dramatic changes in the fungal taxonomy, etiology, epidemiology, and therapy of and outcomes from such infections, including in the transplant setting.
Keywords: Antifungals; Fungal; Infection; Mucorales; Mucormycosis; Rhizopus; Zygomycosis

Mycobacterium tuberculosis infections in solid organ transplantation: Guidelines from the infectious diseases community of practice of the American Society of Transplantation - Subramanian, Aruna K.; Theodoropoulos, Nicole M.; Transplantation, the Infectious Diseases Community of Practice of the American Society of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of tuberculosis in the pre- and post-transplant period. The challenges of screening for both latent and active TB in the setting of transplantation are reviewed. The use of interferon gamma release assays for detection of latent tuberculosis is discussed and compared to tuberculin skin testing. Given the limitations of both testing modality, it is important to consider exposure history and chest imaging. The clinical manifestations of active tuberculosis in transplantation are covered. New recommendations for treatment of latent tuberculosis and active tuberculosis are included.
Keywords: mycobacterial; mycobacterium; transplant; transplantation; tuberculosis

Rare and Emerging Viral Infections in the Transplant Population - Tan, Susanna K.; Waggoner, Jesse J.; Deresinski, Stan (Principles and Practice of Transplant Infectious Diseases, 2019)
Viral infections account for a large proportion of emerging infectious diseases, and the agents included in this group consist of recently identified viruses as well as previously identified viruses with an apparent increase in disease incidence. In transplant recipients, this group can include viruses with no recognized pathogenicity in immunocompetent patients and those that result in atypical or more severe disease presentations in the immunocompromised host. In this chapter, we begin by discussing viral diagnostics and techniques used for viral discovery, specifically as they apply to emerging and rare infections in this patient population. Focus then shifts to specific emerging and re-emerging viruses in the transplant population, including human T-cell leukemia virus 1, rabies, lymphocytic choriomeningitis virus, human bocavirus, parvovirus 4, measles, mumps, orf, and dengue. We have also included a brief discussion on emerging viruses and virus families with few or no reported cases in transplant recipients: monkeypox, nipah and hendra, chikungunya and other alphaviruses, hantavirus and the Bunyaviridae, and filoviruses. Finally, concerns regarding infectious disease complications in xenotransplantation and the reporting of rare viral infections are addressed. With the marked increase in the number of solid organ and hematopoietic stem cell transplants performed worldwide, we expect a corresponding rise in the reports of emerging viral infections in transplant hosts, both from known viruses and those yet to be identified.
Keywords: Emerging infections; Immunocompromised host; Viral discovery

Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice - Te, Helen; Doucette, Karen (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of viral hepatitis in the pre- and post-transplant period. The current guidelines reflect the declining need for hepatitis B immunoglobulin following liver transplant, now replaced with nucleos(t)ide analogues that effectively suppress viral replication for the long term with minimal risk for drug resistance. It describes the limitations of pegylated interferon alpha in the treatment for chronic hepatitis D. The guidelines feature the paradigm shift in the treatment arena of chronic hepatitis C, now consisting of highly effective direct-acting antiviral (DAA) medications that effect a cure almost universally. Its safety profile and easy tolerance have permitted its use in patients with decompensated cirrhosis and/or end-stage renal disease. The high potency of the DAA's has fueled the rapidly expanding utilization of hepatitis C-exposed grafts in non-hepatitis C-infected liver, heart, or kidney recipients within structured protocols, followed by viral eradication with DAA therapy in the peri- or post-transplant period. Chronic hepatitis E has become more recognized in the solid-organ transplant recipients, and the therapeutic approach has been streamlined to start with reduction of immunosuppression, and if indicated afterward, ribavirin monotherapy.
Keywords: antibiotic: antiviral; infection and infectious agents; viral: hepatitis

Antimicrobial Drug Prophylaxis: Challenges and Controversies - Trikha, Gaurav; Nucci, Marcio; Wingard, John R.; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Prevention of infection is important in the susceptible patients undergoing transplantation. Accurate diagnosis continues to be a challenge, and response to treatment is often suboptimal, mainly due to immune defects that cannot be corrected during the course of an infection episode. Antimicrobial drugs are the cornerstone for prevention of opportunistic and other routinely encountered infections in patients undergoing solid organ and hematopoietic stem cell allograft transplantation. However, there are many controversies associated with antimicrobial prophylaxis. In general, antimicrobial prophylaxis is beneficial during periods when the infection risk is highest including the early postoperative period in patients undergoing visceral allograft surgery and those with acute allograft rejection; in HSCT recipients with pre-engraftment neutropenia and those with graft-versus-host disease, to name a few. In a number of other situations, a clear benefit from such innervation is not certain. In this chapter, we present a comprehensive discussion on challenges and controversies associated with antimicrobial prophylaxis in HSCT and SOT recipients.
Keywords: Bacterial; Fungal; Infection; Prevention; Prophylaxis; Transplant; Viral

Histoplasmosis, Coccidioidomycosis, and Diseases Due to Other Endemic Fungi in Transplant Recipients - Vergidis, Pascalis; Hage, Chadi A.; Wheat, L. Joseph (Principles and Practice of Transplant Infectious Diseases, 2019)
Endemic fungi are thermally dimorphic and occur naturally in specific geographic areas. Histoplasmosis, coccidioidomycosis, and blastomycosis are the three major disease entities encountered in North America. Even in endemic areas, disease incidence is low among transplant recipients. Infection is typically acquired via inhalation of molds from the environment. Disseminated infection is more likely to occur in immunocompromised individuals. Definitive diagnosis is established by growing the organism from respiratory secretions, blood, other body fluids, or tissue. With appropriate stains, fungal organisms may be detected directly from clinical specimens. All immunocompromised patients should be treated, usually with a lipid formulation of amphotericin B followed by azole therapy. Donors and recipients should be evaluated for the possibility of active disease before transplantation. Because each endemic fungal infection is unusual outside of a specific geographic area, a careful travel and residence history should be obtained.
Keywords: Histoplasmosis, Coccidioidomycosis, Blastomycosis, Amphotericin B, Itraconazole, Fluconazole

ESCMID-ECMM guideline: diagnosis and management of invasive aspergillosis in neonates and children - Warris, A.; Lehrnbecher, T.; Roilides, E.; Castagnola, E.; Brüggemann, R.J.M.; Groll, A.H. (Clinical Microbiology and Infection, 2019)
Scope: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-speciﬁc guideline for the diagnosis and management of IA in neonates and children.

Early experience with the use of hepatitis C antibody-positive, nucleic acid testing-negative donors in lung transplantation - Watson, Joshua; Mulvihill, Michael S.; Cox, Morgan L.; Rich, Lauren; Wolfe, Cameron R.; Gray, Alice; Hartwig, Matthew G. (Clinical Transplantation, 2019)
Historically, potential lung donors who have detectable antibodies to hepatitis C virus have been declined by most centers due to concern for possible disease transmission. We sought to evaluate hepatitis C viral transmission rates from donors who were known to be HCV Ab positive but HCV NAT negative. We performed a single-center retrospective review of a prospectively collected database for lung transplant recipients at our center including HCV Ab+NAT- donors (approved January 2017). Donor and recipient demographic data were compiled, and records were queried to ascertain rate of seroconversion. During the study period (1/1/17 to 8/9/17), a total of 64 recipients underwent lung transplantation. Thirteen (20%) donors were HCV Ab+NAT-. All recipients of HCV Ab+NAT- grafts were HCV Ab- at the time of transplant. Recipients of grafts from HCV Ab+NAT- donors underwent protocol NAT at 2 and 12 months and all are NAT- to date. One recipient developed reactive HCV Ab at 6 months post-transplant. Follow-up NAT showed HCV RNA to be undetectable. To date, use of HCV Ab+NAT- donors in lung transplantation has yielded favorable outcomes, with evidence of one transient seroconversion suggesting this practice may increase access to life-saving transplantation to those in need.

Enterobacteriaceae in Transplantation - Whitaker, Kathryn; Cluzet, Valerie; Blumberg, Emily A. (Principles and Practice of Transplant Infectious Diseases, 2019)
Enterobacteriaceae comprise important pathogens for recipients of solid organ and hematopoietic stem cell transplants. Especially common in the early posttransplant period when transplant recipients are still hospitalized, they can occur at any time following the procedure. Increasing frequency of colonization and invasive disease due to antimicrobial-resistant pathogens has been described in recipients of solid organ and hematopoietic stem cell transplants. In solid organ transplant recipients, surgical considerations may affect the development of these infections, and transplant organ-specific infections are frequently seen. In stem cell recipients, blood stream infections are among the most common manifestations. In cases of respiratory tract, superficial wound, and urinary tract isolation of Enterobacteriaceae, it is important to differentiate colonization from true infection. The choice of appropriate antimicrobials should include consideration of the risk for antimicrobial resistance. Source control may be critical to cure infection, especially when the patient has either line-related bloodstream infection or surgical site/wound involvement. Transplant recipients may also be at risk for infection with Enterobacteriaceae that are not typically considered pathogenic in the normal host; consequently, all cultures should be carefully interpreted with respect to clinical presentation and the source of the culture.
Keywords: Citrobacter spp.; Enterobacter spp.; Escherichia coli; Hematopoietic stem cell transplantation; Klebsiella spp.; Proteus spp.; Salmonella spp.; Serratia spp.; Shigella spp.; Solid organ transplantation; Yersinia spp.

Donor-derived infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice - Wolfe, Cameron R.; Ison, Michael G.; Practice, the AST Infectious Diseases Community of (Clinical Transplantation, 2019)
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation will review the current state of the art of donor-derived infections. Specifically, the guideline will summarize standardized definitions and approaches to defining imputability, updated data on the epidemiology of donor-derived infections, and approaches to risk mitigation against transmission of infections. This update will additionally provide guidance on the use of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors in non-viremic recipients, donors with endemic infections, and donors with bacteremia, meningitis, and encephalitis. Lastly, the guidance will summarize an approach to recipients with a suspected donor-derived infection.
Keywords: complication; donor-derived infections; donors and donation; infectious

Complications Arising from Preparatory Conditioning Regimens for Stem Cell Transplantation - Zain, Jasmine; Bar, Merav; Safdar, Amar (Principles and Practice of Transplant Infectious Diseases, 2019)
Hematopoietic stem cell transplantation (HSCT) has the potential to provide long-term survival and potential cure in patients with hematological malignancies and nonmalignant hematologic and autoimmune disorders. Conditioning regimens are designed to make room for the stem cell allograft by ablation of hosts’ immune system with the objective of sustained foreign immune cell engraftment. However, a number of short-term and long-term complications are associated with regimens used for preparatory conditioning in patients prior to allogenic stem cell infusion. Myeloablative conditioning regimens may cause significant toxicities, which include pancytopenia and injury to the orointestinal tract, brain, heart, liver, kidneys, and lungs. In order to mitigate such adverse events, reduced-intensity regimens have been developed. Emesis, anorexia, mucositis, and diarrhea are common orointestinal tract adverse events; sinusoidal obstruction syndrome is the main hepatotoxicity, and kidney injury may be either acute, or chronic. Treatment-induced defects in innate and adaptive immune function make patients susceptible to a variety of infections. Neurologic complications such as encephalopathy, seizures, cerebrovascular events, cognitive changes, and peripheral neuropathy are also not uncommon. Whereas early cardiac complications include congestive heart failure, arrhythmias, pericardial effusions, and endocarditis; whereas late cardiac complication also includes valvular heart disease. Lungs are a frequent site for such complications and include, acute pneumonitis, noncardiogenic pulmonary edema, diffuse alveolar hemorrhage, idiopathic pneumonia, as well as late obstructive and restrictive lung disease. Increased risk for bleeding may occur due to severe thrombocytopenia; additionally, hemolytic complications secondary to thrombotic microangiopathy may also be seen. Conditioning regimens may adversely affect the endocrine function such as, growth and skeletal development, metabolic functions, gonadal and sexual function, and fertility. Finally, high-dose chemotherapy and radiation therapy used in preparatory regimen may contribute towards an increased risk for cancers, mostly noted late after transplantation. In this chapter, a detailed review of complications associated with conditioning regimens given in preparation for stem cell allograft transplantation is presented.
Keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Infections; Organ toxicity; Preparatory conditioning regimens; Reduced-intensity preparatory conditioning regimens; Secondary malignancies

Endovascular Infections and Endocarditis - Zingg, Walter; Pittet, Didier (Principles and Practice of Transplant Infectious Diseases, 2019)
Acute bloodstream infection (BSI) is one of the most severe forms of infection. BSI may be primary or secondary and community-acquired or healthcare-associated. BSI is frequently observed among immunocompromised and critically ill patients, but is rarely asymptomatic and may be associated with multiple organ failure (Pittet et al. JAMA. 1994;271(20):1598–601; Edmond et al. Clin Infect Dis. 1999;29(2):239–44; Marshall et al. Crit Care Med. 2003;31(5):1560–7). Infective endocarditis (IE) is either acute or subacute, the latter being more common with underlying vascular disease.
Keywords: Bloodstream infection; High-grade bacteremia; Immunocompromised host; Infective endocarditis; Transplantation; Vascular disease

A Systematic Review of Single-Dose Aminoglycoside Therapy for Urinary Tract Infection: Is It Time To Resurrect an Old Strategy? - Goodlet, Kellie J.; Benhalima, Fatima Z.; Nailor, Michael D. (Antimicrobial Agents and Chemotherapy, 2018)
Increasing bacterial resistance and poor patient adherence rates limit the effectiveness of conventional antibiotic therapies for urinary tract infection (UTI). The objective of this study was to investigate whether a single aminoglycoside dose adequately treated UTI., Increasing bacterial resistance and poor patient adherence rates limit the effectiveness of conventional antibiotic therapies for urinary tract infection (UTI). The objective of this study was to investigate whether a single aminoglycoside dose adequately treated UTI. A systematic search of PubMed/MEDLINE and Google Scholar databases was performed through September 2018 for English language original research articles assessing the efficacy of one-time parenteral aminoglycoside as UTI monotherapy. Of 252 potentially relevant studies, 13 studies met the inclusion criteria, representing 13,804 patients. Patient ages ranged from 2 weeks to >70 years; both inpatient and outpatient settings were represented. Cystitis was more common than pyelonephritis, and more females were represented than males. Escherichia coli was the most commonly isolated uropathogen. The pooled microbiologic cure rate with single-dose aminoglycoside therapy was 94.5% ± 4.3%. Cure was sustained (no recurrence) for 73.4% ± 9.6% of patients at day 30. Lower cure rates were observed among patients with radiographic urinary tract abnormality (chi-square P < 0.01). Across all studies, 63/13,804 (0.5%) cases of nephrotoxicity, vestibular toxicity, or injection site reaction were reported; no hearing loss was observed. Single-dose aminoglycoside therapy appears to be an effective treatment option for lower UTI in nonseptic patients, with minimal toxicity. Additional studies would be beneficial to confirm efficacy for pyelonephritis. When resistance to first-line UTI agents is endemic, aminoglycosides may serve as β-lactam- and fluoroquinolone-sparing options.

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery - Szyszkowitz, Alexander; Zurl, Christoph; Herzeg, Anna; Berger, Anton; Gemes, Geza; Mitteregger, Martin; Prüller, Florian; Prattes, Juergen; Zollner-Schwetz, Ines; Valentin, Thomas; Hoenigl, Martin; Krause, Robert (Open Forum Infectious Diseases, 2018)
AbstractBackground. 1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some pro

Pulmonary Involvement in Brucellosis, a Rare Complication of Renal Transplant: Case Report and Brief Review - Ay, Nurettin; Kaya, Safak; Anil, Melih; Alp, Vahhac; Beyazit, Unal; Yuksel, Enver; Danis, Ramazan (Experimental and Clinical Transplantation: Official Journal of the Middle East Society for Organ Transplantation, 2018)
Brucellosis, a disease endemic in many countries including Turkey, is a systemic infectious disease. Brucellosis is rare in renal transplant recipients. Only 4 cases have been reported in the literature. In this report, we describe the clinical manifestations and laboratory findings of a brucellosis case with pulmonary involvement in a renal transplant recipient. A 20-year-old man who had a living-donor kidney transplant 4 months earlier presented to our transplant clinic with fever, cough, and right flank pain. Clarithromycin and ceftriaxone were started for the diagnosis of pneumonia. However, piperacillin/tazobactam, meropenem plus teicoplanin, and antituberculosis treatment were continued because the patient was unresponsive to the initial therapy. Serum Brucella agglutination titer was found to be 1/320. Treatment was started with a 6-week course of oral doxycycline and rifampin, resulting in cure. Brucellosis and especially its pulmonary involvement are rare after kidney transplant. However, in endemic areas,it should be considered as it mimics several other infectious diseases.
Keywords: Adult; Anti-Bacterial Agents; Brucellosis; Humans; Kidney Transplantation; Male; Renal Insufficiency, Chronic; Respiratory Tract Infections; Treatment Outcome; Young Adult

Mutagenesis in Norovirus in Response to Favipiravir Treatment - Ruis, Christopher; Brown, Li-An K.; Roy, Sunando; Atkinson, Claire; Williams, Rachel; Burns, Siobhan O.; Yara-Romero, Erika; Jacobs, Michael; Goldstein, Richard; Breuer, Judith; Lowe, David M. (New England Journal of Medicine, 2018)
Favipiravir for Chronic Norovirus Infection Norovirus may cause chronic diarrhea, especially in immunosuppressed patients. There is no established treatment. In this case report, favipiravir is shown to have some evidence of activity and to induce some selective pressure on the virus.

Fecal Microbiota Transplantation: Restoring the Injured Microbiome after Allogeneic Hematopoietic Cell Transplantation - DeFilipp, Zachariah; Hohmann, Elizabeth; Jenq, Robert R.; Chen, Yi-Bin (Biology of Blood and Marrow Transplantation, 2018)
ABSTRACT Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, whether microbiome-directed interventions will be able to impact important clinical endpoints remains unknown. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the use of FMT as treatment for Clostridium difficile infection and acute graft-versus-host disease, and also as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in allo-HCT recipients.

Interagency registry for mechanically assisted circulatory support report on the total artificial heart - Arabía, Francisco A.; Cantor, Ryan S.; Koehl, Devin A.; Kasirajan, Vigneshwar; Gregoric, Igor; Moriguchi, Jaime D.; Esmailian, Fardad; Ramzy, Danny; Chung, Joshua S.; Czer, Lawrence S.; Kobashigawa, Jon A.; Smith, Richard G.; et al. (The Journal of Heart and Lung Transplantation, 2018)
Background We sought to better understand the patient population who receive a temporary total artificial heart (TAH) as bridge to transplant or as bridge to decision by evaluating data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. Methods We examined data related to survival, adverse events, and competing outcomes from patients who received TAHs between June 2006 and April 2017 and used hazard function analysis to explore risk factors for mortality. Results Data from 450 patients (87% men; mean age, 50 years) were available in the INTERMACS database. The 2 most common diagnoses were dilated cardiomyopathy (50%) and ischemic cardiomyopathy (20%). Risk factors for right heart failure were present in 82% of patients. Most patients were INTERMACS Profile 1 (43%) or 2 (37%) at implantation. There were 266 patients who eventually underwent transplantation, and 162 died. Overall 3-, 6-, and 12-month actuarial survival rates were 73%, 62%, and 53%, respectively. Risk factors for death included older age (p = 0.001), need for pre-implantation dialysis (p = 0.006), higher creatinine (p = 0.008) and lower albumin (p < 0.001) levels, and implantation at a low-volume center (≤10 TAHs; p < 0.001). Competing-outcomes analysis showed 71% of patients in high-volume centers were alive on the device or had undergone transplantation at 12 months after TAH implantation vs 57% in low-volume centers (p = 0.003). Conclusions Patients receiving TAHs have rapidly declining cardiac function and require prompt intervention. Experienced centers have better outcomes, likely related to patient selection, timing of implantation, patient care, and device management. Organized transfer of knowledge to low-volume centers could improve outcomes.

Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections: A Randomized Clinical Trial - Hooton, Thomas M.; Vecchio, Mariacristina; Iroz, Alison; Tack, Ivan; Dornic, Quentin; Seksek, Isabelle; Lotan, Yair (JAMA Internal Medicine, 2018)
Increased hydration is often recommended as a preventive measure for women with recurrent cystitis, but supportive data are sparse.To assess the efficacy of increased daily water intake on the frequency of recurrent cystitis in premenopausal women.Randomized, open-label, controlled, 12-month trial at a clinical research center (years 2013-2016). Among 163 healthy women with recurrent cystitis (≥3 episodes in past year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were excluded and 140 assigned to water or control group. Assessments of daily fluid intake, urinary hydration, and cystitis symptoms were performed at baseline, 6- and 12-month visits, and monthly telephone calls.Participants were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L of water daily (water group) or no additional fluids (control group) for 12 months.Primary outcome measure was frequency of recurrent cystitis over 12 months. Secondary outcomes were number of antimicrobial regimens used, mean time interval between cystitis episodes, and 24-hour urinary hydration measurements.The mean (SD) age of the 140 participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes in the previous year was 3.3 (0.6). During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001). Overall, there were 327 cystitis episodes, 111 in the water group and 216 in the control group. The mean number of antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2) and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95% CI, 1.3-2.1; P < .001). The mean time interval between cystitis episodes was 142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with a difference in means of 58.4 (95% CI, 39.4-77.4; P < .001). Between baseline and 12 months, participants in the water group, compared with those in the control group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P < .001) and voids (2.4 [0.2] vs −0.1 [0.2]; P < .001) and decreased urine osmolality (−402.8 [19.6] vs −24.0 [19.5] mOsm/kg; P < .001).Increased water intake is an effective antimicrobial-sparing strategy to prevent recurrent cystitis in premenopausal women at high risk for recurrence who drink low volumes of fluid daily.ClinicalTrials.gov identifier: NCT02444975

Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions - Lionakis, Michail S.; Lewis, Russell E.; Kontoyiannis, Dimitrios P. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2018)
Although the widespread use of mold-active agents (especially the new generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic, and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including comorbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.
Keywords: Adult; Antifungal Agents; Chemoprevention; Disease Management; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Prospective Studies; Risk Factors; Transplantation, Homologous; Triazoles

Acute Toxoplasma Dissemination With Encephalitis in the Era of Biological Therapies - Gharamti, Amal A; Rao, Amy; Pecen, Paula E; Henao-Martínez, Andrés F; Franco-Paredes, Carlos; Montoya, José G (Open Forum Infectious Diseases, 2018)
We report the case of a 65-year-old patient with pseudolymphoma who developed acute toxoplasmosis following 6 cycles of rituximab and bendamustine therapy. Acute toxoplasmosis in the setting of biological response modifiers, rather than reactivation, is a unique unreported infection. The patient developed severe disease with multi-organ involvement, including retinitis, myocarditis, and myositis. We discuss the clinical findings, epidemiology, and laboratory diagnosis.

Cardiac transplantation from non-viremic hepatitis C donors - Patel, Snehal R.; Madan, Shivank; Saeed, Omar; Sims, Daniel B.; Shin, J. Julia; Nucci, Cecilia; Borukhov, Edward; Goldstein, Doctor Y.; Jakobleff, William; Forest, Stephen; Vukelic, Sasa; Murthy, Sandhya; et al. (The Journal of Heart and Lung Transplantation, 2018)
BACKGROUND Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab+/NAT+) and those who have cleared HCV and are no longer viremic (HCV Ab+/NAT–). The American Society of Transplantation recently recommended that HCV Ab+/NAT– donors be considered non-infectious and safe for transplantation. We present our initial experience with such donors. METHODS All patients were counseled regarding donor HCV antibody (Ab) and NAT. Transplant recipients were tested post-transplant at 1 week and at 1, 3, and 6 months for HCV seropositivity and viremia. We also analyzed the UNOS database to determine the potential impact of widespread acceptance of HCV Ab+/NAT– organs. RESULTS Fourteen HCV Ab‒ subjects received hearts from HCV Ab+/NAT– donors in 2017. Over a median follow-up of 256 (192 to 377) days, 3 patients developed a reactive HCV Ab, yet none had a detectable HCV viral load during prospective monitoring at any time. Analysis of the UNOS database for the calendar year 2016 revealed that only 7 (3%) of 220 HCV Ab+/NAT– donors were accepted for heart transplantation. CONCLUSIONS We have demonstrated the feasibility of utilizing HCV Ab+/NAT– donors for cardiac transplantation without recipient infection. A small percentage of recipients developed HCV Ab without evidence of viremia, possibly consistent with a biological false reactive test, as has been seen in other settings. Large-scale validation of our data may have a significant impact on transplantation rates.

Oral vancomycin prophylaxis is highly effective in preventing Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients - Ganetsky, Alex; Han, Jennifer H.; Hughes, Mitchell E.; Babushok, Daria V.; Frey, Noelle V.; Gill, Saar I.; Hexner, Elizabeth O.; Loren, Alison W.; Luger, Selina M.; Mangan, James K.; Martin, Mary Ellen; Smith, Jacqueline; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2018)
Background: Clostridiumdifficile infection (CDI) is a leading cause of infectious complications in allogeneic hematopoietic cell transplant recipients (alloHCT). We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. Methods: We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin compared to no prophylaxis in 145 consecutive adult alloHCT recipients at the University of Pennsylvania between April 2015 and November 2016. Patients received oral vancomycin 125 mg twice daily starting on admission and continued until discharge. The primary outcome of interest was the association between oral vancomycin prophylaxis and CDI diagnosis. Secondary outcomes included graft-versus-host-disease (GVHD) and relapse. Results: There were no cases of CDI in patients that received prophylaxis 0/90 (0%) whereas 11/55 (20%) patients who did not receive prophylaxis developed CDI (P<0.001). Oral vancomycin prophylaxis was not associated with a higher risk of acute grade 2 - 4 [subhazard ratio (sHR) 1.59; 95% confidence interval (CI), 0.88 - 2.89; P=0.12], grade 3 - 4 (sHR 0.65; 95% CI, 0.25 - 1.66; P=0.36), or grade 2 - 4 gastrointestinal GVHD (sHR 1.95; 95% CI, 0.93 - 4.07; P=0.08) at day 180 post-transplant. No associations between oral vancomycin and relapse or survival were observed.

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents - Hayden, Frederick G.; Sugaya, Norio; Hirotsu, Nobuo; Lee, Nelson; Jong, Menno D. de; Hurt, Aeron C.; Ishida, Tadashi; Sekino, Hisakuni; Yamada, Kota; Portsmouth, Simon; Kawaguchi, Keiko; Shishido, Takao; et al. (New England Journal of Medicine, 2018)
Original Article from The New England Journal of Medicine — Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update - Taplitz, Randy A.; Kennedy, Erin B.; Bow, Eric J.; Crews, Jennie; Gleason, Charise; Hawley, Douglas K.; Langston, Amelia A.; Nastoupil, Loretta J.; Rajotte, Michelle; Rolston, Kenneth V.; Strasfeld, Lynne; Flowers, Christopher R. (Journal of Clinical Oncology, 2018)
PurposeTo provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment.MethodsASCO and IDSA convened an update Expert Panel and conducted a systematic review of relevant studies from May 2011 to November 2016. The guideline recommendations were based on the review of evidence by the Expert Panel.ResultsSix new or updated meta-analyses and six new primary studies were added to the updated systematic review.RecommendationsAntibacterial and antifungal prophylaxis is recommended for patients who are at high risk of infection, including patients who are expected to have profound, protracted neutropenia, which is defined as < 100 neutrophils/µL for > 7 days or other risk factors. Herpes simplex virus–seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir. Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage). Treatment with a nucleoside reverse transcription inhibitor (eg, entecavir or tenofovir) is recommended for patients at high risk of hepatitis B virus reactivation. Recommendations for vaccination and avoidance of prolonged contact with environments that have high concentrations of airborne fungal spores are also provided within the updated guideline. Additional information is available at www.asco.org/supportive-care-guidelines.

Safe Living Following Solid Organ Transplantation - Blair, Barbra M. (Infectious Disease Clinics, 2018)
Keywords: Food safety; Infection prevention; Solid organ transplantation; Travel advice; Vaccination

Management of Viral Hepatitis in Solid Organ Transplant Recipients - Buganza-Torio, Elizabeth; Doucette, Karen Elizabeth (Infectious Disease Clinics, 2018)
Keywords: Hepatitis B virus; Hepatitis C virus; Hepatitis E virus; Kidney transplantation; Liver transplantation; Thoracic transplantation

Immunization of Solid Organ Transplant Candidates and Recipients: A 2018 Update - Donato-Santana, Christian; Theodoropoulos, Nicole M. (Infectious Disease Clinics, 2018)
Keywords: Immunization; Immunosuppressed; Solid organ transplant; Vaccine

Management of BK Polyomavirus Infection in Kidney and Kidney-Pancreas Transplant Recipients: A Review Article - Elfadawy, Nissreen; Yamada, Masaaki; Sarabu, Nagaraju (Infectious Disease Clinics, 2018)
Keywords: BK virus; BKV-associated nephropathy (BKVAN); Kidney transplantation; Polyomavirus

Prevention and Management of Tuberculosis in Solid Organ Transplant Recipients - Epstein, David J.; Subramanian, Aruna K. (Infectious Disease Clinics, 2018)
Keywords: Donor derived infections; Latent tuberculosis infection; Opportunistic infections; Solid organ transplantation; Tuberculosis

Is This Organ Donor Safe?: Donor-Derived Infections in Solid Organ Transplantation - Fischer, Staci A. (Infectious Disease Clinics, 2018)
Keywords: Donor-derived infections; Donor-transmitted infections; Lymphocytic choriomeningitis virus; Organ donor screening; Transplant infections

Management of Strongyloides in Solid Organ Transplant Recipients - Hayes, Justin; Nellore, Anoma (Infectious Disease Clinics, 2018)
Keywords: Antihelminthic therapy; Autoinfection; Corticosteroids; Hyperinfection syndrome; Strongyloides; Th2 immune response; Transplant

Prevention and Treatment of Cytomegalovirus Infections in Solid Organ Transplant Recipients - Koval, Christine E. (Infectious Disease Clinics, 2018)
Keywords: CMV; CMV prophylaxis; CMV treatment; Cytomegalovirus; Herpesvirus infection; Solid organ transplantation

Mold Infections in Solid Organ Transplant Recipients - Lemonovich, Tracy L. (Infectious Disease Clinics, 2018)
Keywords: Antifungal; Aspergillosis; Fusariosis; Invasive fungal infections; Mucormycosis; Transplant

Management of Mycobacterium Other than Tuberculosis in Solid Organ Transplantation - Malinis, Maricar F. (Infectious Disease Clinics, 2018)
Keywords: Mycobacterium other than tuberculosis; Solid organ transplantation; Treatment

Endemic Mycoses in Solid Organ Transplant Recipients - Nel, Jeremy S.; Bartelt, Luther A.; Duin, David van; Lachiewicz, Anne M. (Infectious Disease Clinics, 2018)
Keywords: Blastomycosis; Coccidioidomycosis; Endemic mycoses; Histoplasmosis; Solid organ transplant

Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients - Pouch, Stephanie M.; Friedman-Moraco, Rachel J. (Infectious Disease Clinics, 2018)
Keywords: Antimicrobial stewardship; Clostridium difficile infection; Fecal microbiota transplant; Infection control; Prevention; Solid organ transplant; Treatment

Human Immunodeficiency Virus Organ Transplantation - Taege, Alan J. (Infectious Disease Clinics, 2018)
Keywords: HIV; HIV positive to positive organ transplantation; Hepatitis C virus; Organ rejection; Organ transplantation

Yeast Infections in Solid Organ Transplantation - Taimur, Sarah (Infectious Disease Clinics, 2018)
Keywords: Cryptococcosis after organ transplant; Emerging fungal pathogens in organ transplant; Invasive candidiasis after organ transplant; Yeast infections in organ transplants

Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation - Chen, Kaiwen; Cheng, Matthew P.; Hammond, Sarah P.; Einsele, Hermann; Marty, Francisco M. (Blood Advances, 2018)
Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.

Chimeric Antigen Receptor Therapy - June, Carl H.; Sadelain, Michel (New England Journal of Medicine, 2018)
Chimeric Antigen Receptor T Cells This review addresses T-cell engineering and synthetic immunity, with a focus on producing durable remissions in patients with treatment-refractory tumors. Toxic effects of chimeric antigen receptor therapies include cytokine release syndrome and neurologic dysfunction.

ESTRATEGIAS PARA UNA VIDA MÁS SEGURA DESPUÉS DEL TRASPLANTE - Avery, Robin; Chen, Sharon; Gans, Hayley; Soave, Rosemary (2018)

Strategies for Safer Living After Transplantation - Avery, Robin; Chen, Sharon; Gans, Hayley; Soave, Rosemary (2018)

Guide to Safe Travel after Transplant - Yadav, Pallavi; Baddley, John (2018)

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation - Kotton, Camille N.; Kumar, Deepali; Caliendo, Angela M.; Huprikar, Shirish; Chou, Sunwen; Danziger-Isakov, Lara; Humar, Atul; Group, on behalf of the The Transplantation Society International CMV Consensus (Transplantation, 2018)
Despite recent advances, cytomegalovirus (CMV) infections remain one of the most common complications affecting solid organ transplant recipients, conveying higher risks of complications, graft loss, morbidity, and mortality. Research in the field and development of prior consensus guidelines supported by The Transplantation Society has allowed a more standardized approach to CMV management. An international multidisciplinary panel of experts was convened to expand and revise evidence and expert opinion-based consensus guidelines on CMV management including prevention, treatment, diagnostics, immunology, drug resistance, and pediatric issues. Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease. The following report summarizes the updated recommendations.

Prevalence of Sexually Transmitted Diseases in Asymptomatic Renal Transplant Recipients - Sarier, Mehmet; Sepin Ozen, Nevgun; Guler, Hicran; Duman, Ibrahim; Yüksel, Yücel; Tekin, Sabri; Yavuz, Asuman Havva; Yucetin, Levent; Erdogan Yilmaz, Mine (Experimental and Clinical Transplantation: Official Journal of the Middle East Society for Organ Transplantation, 2018)
OBJECTIVES: Sexually transmitted diseases, which may be asymptomatic, have the potential to cause serious health problems in renal transplant recipients. The aim of this study was to determine the prevalence of sexually transmitted diseases in sexually active asymptomatic renal transplant patients by using real-time multiplex polymerase chain reaction assays. MATERIALS AND METHODS: This prospective controlled study was conducted between November 2016 and January 2017 in our hospital. Our study group included 80 consecutive, sexually active asymptomatic patients (40 men and 40 women) who had undergone renal transplant in our hospital and who presented to our outpatient clinic for routine follow-up. We also included a control group of 80 consecutive, sexually active nontransplant patients (40 men and 40 women). All patient samples were tested for Gardnerella vaginalis and obligate anaerobes (Prevotella bivia, Porphyromonas species), Candida species, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma species, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2, and Cytomegalovirus by real-time multiplex polymerase chain reaction. RESULTS: The prevalences of infection with Gardnerella vaginalis and obligate anaerobes (P = .043), Ureaplasma species (P = .02), and Cytomegalovirus (P = .016) were found to be significantly higher in the study group versus the control group. However, there was no difference between the 2 groups regarding the prevalence of Mycoplasma infection (P = .70). CONCLUSIONS: Sexually transmitted diseases may occur more frequently in sexually active asymptomatic renal transplant recipients than in nontransplanted individuals. Real-time multiplex polymerase chain reaction analysis may be a suitable method for determining these pathogens.

Emergomyces canadensis, a Dimorphic Fungus Causing Fatal Systemic Human Disease in North America - Schwartz, Ilan S.; Sanche, Stephen; Wiederhold, Nathan P.; Patterson, Thomas F.; Sigler, Lynne (Emerging Infectious Diseases, 2018)
We report 4 patients in North America with disease caused by Emergomyces canadensis, a newly proposed species of pathogenic dimorphic fungus. Affected persons were immunocompromised; lived in Saskatchewan, Colorado, and New Mexico; and had systemic disease involving blood, skin, cervix, lung, and lymph node. Two cases were fatal.

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance - Terrault, Norah A.; Lok, Anna S. F.; McMahon, Brian J.; Chang, Kyong-Mi; Hwang, Jessica P.; Jonas, Maureen M.; Brown, Robert S. Jr; Bzowej, Natalie H.; Wong, John B. (Hepatology, 2018)
An abstract is unavailable.

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) - McDonald, L. Clifford; Gerding, Dale N.; Johnson, Stuart; Bakken, Johan S.; Carroll, Karen C.; Coffin, Susan E.; Dubberke, Erik R.; Garey, Kevin W.; Gould, Carolyn V.; Kelly, Ciaran; Loo, Vivian; Shaklee Sammons, Julia; et al. (Clinical Infectious Diseases, 2018)
A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update - Taplitz, Randy A.; Kennedy, Erin B.; Bow, Eric J.; Crews, Jennie; Gleason, Charise; Hawley, Douglas K.; Langston, Amelia A.; Nastoupil, Loretta J.; Rajotte, Michelle; Rolston, Kenneth; Strasfeld, Lynne; Flowers, Christopher R. (Journal of Clinical Oncology, 2018)
PurposeTo provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer.MethodsASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel.ResultsSix new or updated meta-analyses and six new primary studies were added to the updated systematic review.RecommendationClinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment.Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America - Clemente, Wanessa Trindade; Pierrotti, Lígia Camera; Abdala, Edson; Morris, Michele I.; Azevedo, Luiz S.; López-Vélez, Rogelio; Cuenca-Estrella, Manuel; Torre-Cisneros, Julian; Petersen, Eskild; Camargo, Luis Fernando A.; Wright, Alissa Jade; Beeching, Nicholas J.; et al. (Transplantation, 2018)
The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America - Clemente, Wanessa Trindade; Pierrotti, Lígia Camera; Abdala, Edson; Morris, Michele I.; Azevedo, Luiz S.; López-Vélez, Rogelio; Cuenca-Estrella, Manuel; Torre-Cisneros, Julian; Petersen, Eskild; Camargo, Luis Fernando A.; Wright, Alissa Jade; Beeching, Nicholas J.; et al. (Transplantation, 2018)
The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways - Chamilos, Georgios; Lionakis, Michail S; Kontoyiannis, Dimitrios P (Clinical Infectious Diseases, 2018)

ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients - Cesaro, Simone; Dalianis, Tina; Hanssen Rinaldo, Christine; Koskenvuo, Minna; Pegoraro, Anna; Einsele, Hermann; Cordonnier, Catherine; Hirsch, Hans H.; Akova, Murat; Aljurf, Mahmoud; Averbuch, Dina; Barnes, Rosemary; et al. (Journal of Antimicrobial Chemotherapy, 2018)
AbstractObjectives. To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT.Methods. Revi

Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin–resistant Enterococcus spp (VRE): a single-center university hospital experience - Shah, Kairav J.; Cherabuddi, Kartikeya; Shultz, Joseph; Borgert, Samuel; Ramphal, Reuben; Klinker, Kenneth P. (International Journal of Antimicrobial Agents, 2018)
Vancomycin-resistant enterococci (VRE) are a common cause of urinary tract infections (UTIs) and are typically multidrug resistant, including ampicillin. This retrospective study evaluated outcomes of 84 adult patients hospitalized between January 2007 and December 2015 with ampicillin– and vancomycin–resistant enterococcus isolates causing UTI and treated with ampicillin. Treatment response was classified as clinical cure and microbiological eradication. Clinical cure was achieved in 88.1% (74/84) of patients. In patients with follow–up cultures, microbiological eradication was achieved in 86% (50/58) of patients. Cure rates were similar in patients with indwelling urinary catheters (n = 45) receiving catheter exchange/removal (90.47%; 19/21) versus catheter retention (87.5%; 21/24). Presence of co–morbidities, such as diabetes and chronic kidney disease, were not associated with increased risk of treatment failure. Immunocompromised patients achieved lower cure rates of 78.1% (25/32) compared with 94.2% (49/52) among those without immune impairment (P = 0.038). Presence of an underlying urinary tract abnormality was also associated with a lower cure rate of 71.4% (15/21) compared with 93.7% (59/63) in those without urinary tract abnormalities (P = 0.0135). Overall cure rates remained high in all groups providing good evidence to support ampicillin for the treatment of complicated UTI caused by ampicillin– and vancomycin–resistant enterococci.
Keywords: Ampicillin; Antimicrobial stewardship; Cystitis; UTI; VRE; Vancomycin-resistant enterococci

FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration (2018)

Donor derived Mycobacterium tuberculosis infection after solid-organ transplantation: A comprehensive review - Abad, Cybele L. R.; Razonable, Raymund R. (Transplant Infectious Disease, 2018)
Background Mycobacterium tuberculosis may be transmitted via the allograft to cause a morbid and potentially fatal infection after solid organ transplantation (SOT). We reviewed all reported cases of donor-derived tuberculosis (DDTB) to provide an update on its epidemiology, clinical course, and outcome after SOT. Methods MEDLINE, OVID, and EMBASE were reviewed from its inception until December 31, 2016 using key words donor-derived infection, tuberculosis and solid organ transplant or transplantation. Results We retrieved 36 cases of proven (n = 17), probable (n = 8), and possible (n = 11) DDTB among 16 lung, 13 kidney, 6 liver, and 1 heart recipients. Most patients were male (21/35, 60%) with median age of 48 (range 23-68) years. Median time to clinical presentation or diagnosis was 2.7 months (range 0.2-29). The most common donor risk factor was residence in a TB-endemic area (13/28, 46.4%). Fever was the most frequent presenting symptom (20/36, 56.5%). Diagnosis of tuberculosis was mostly made via AFB smear or mycobacterial culture (30/36, 83.3%). Allograft involvement was expectedly common; there were almost equal proportions of pulmonary (36%), extra-pulmonary (28%) and disseminated (36%) cases. All cases of pulmonary TB were identified only among lung transplant recipients. The median duration of TB treatment was 10.5 (range 3-24) months. Graft loss occurred in four (4/22, 18.2%) patients. All-cause mortality was 25% (9/36); four of nine deaths were attributed to TB. Conclusions Donor-derived TB presents early after SOT, most commonly as fever, and carries a high mortality risk. Donors should be screened, with particular attention to TB risk factors. Fever during the early post-operative period should prompt a thorough evaluation for DDTB in endemic regions and among patients with “at-risk” donors.
Keywords: Mycobacterium tuberculosis; donor derived TB; solid organ transplant

Editorial for ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective - Aguado, J.M.; Manuel, O. (Clinical Microbiology and Infection, 2018)

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Cell surface receptors and associated signaling pathways) - Aguilar-Company, J.; Fernández-Ruiz, M.; García-Campelo, R.; Garrido-Castro, A.C.; Ruiz-Camps, I. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents) - Baddley, J.W.; Cantini, F.; Goletti, D.; Gómez-Reino, J.J.; Mylonakis, E.; San-Juan, R.; Fernández-Ruiz, M.; Torre-Cisneros, J. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety proﬁle of agents targeting tumour necrosis factor-a (TNF-a) and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: Preclinical and clinical evidence indicate that anti-TNF-a therapy (inﬂiximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-a therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No beneﬁt is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. inﬂuenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measlesemumpserubella) may be contraindicated in people receiving anti-TNF-a therapy, although additional data are needed before deﬁnitive recommendations can be made.

Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection - Cherrier, Lauren; Nasar, Aasya; Goodlet, Kellie J.; Nailor, Michael D.; Tokman, Sofya; Chou, Sunwen (American Journal of Transplantation, 2018)
Following a year of valganciclovir prophylaxis, a lung transplant recipient developed cytomegalovirus (CMV) infection that became resistant to ganciclovir, as confirmed by detection of UL97 kinase mutation M460V and a previously uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now shown to confer ganciclovir and cidofovir resistance. As predicted from the viral genotype, foscarnet therapy was effective, but resumption of valganciclovir as secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log10 copies/mL several weeks later. Valganciclovir was then replaced by letermovir, resulting in gradual viral load reduction in the first 5 weeks to below the quantitation limit (2.7 log10 copies/mL) for 1 week, followed by 10 weeks of rising viral loads reaching 4.3 log10 copies/mL while on letermovir. At this point, CMV genotypic testing revealed UL56 mutation C325Y, which confers absolute resistance to letermovir. Retreatment with foscarnet was successful. This case adds to the considerable list of proven ganciclovir resistance mutations, and provides an early experience with letermovir resistance after off-label therapeutic use. This experience is consistent with in vitro observations of rapid emergence of letermovir-resistant CMV after drug exposure.
Keywords: antibiotic: antiviral; antibiotic: antiviral-ganciclovir/valganciclovir; clinical research/practice; infection and infectious agents - viral: Cytomegalovirus (CMV); infectious disease; off-label drug use; translational research/science

Letermovir successfully used for secondary prophylaxis in a heart transplant recipient with ganciclovir-resistant cytomegalovirus syndrome (UL97 mutation) - Chong, Pearlie P.; Teiber, Dagny; Prokesch, Bonnie C.; Arasaratnam, Reuben J.; Peltz, Matthias; Drazner, Mark H.; Garg, Sonia (Transplant Infectious Disease, 2018)
Letermovir was approved by the Food and Drug Administration (FDA) in November 2017 for use in adult cytomegalovirus (CMV)-seropositive allogeneic stem cell transplant (SCT) recipients for primary prophylaxis of CMV infection and disease. We report off-label use of letermovir for secondary prophylaxis of genotype-confirmed ganciclovir-resistant cytomegalovirus (CMV) syndrome (UL 97 mutation [C603W]) in a heart transplant recipient initially treated with intravenous cidofovir followed by foscarnet, both discontinued due to unacceptable toxicities.
Keywords: UL97 mutation; cytomegalovirus; ganciclovir resistance; heart transplant; letermovir

Sexual acquisition of HIV infection after solid organ transplantation: Late presentation and potentially fatal complications - Cristelli, M.p.; Mazolin, M.a.; Manzardo, C.; Ribeiro, M.s.j.; Cofán, F.; Santos, D.w.c.; Castel, M.a.; Tedesco-Silva, H.; Moreno, A.; Diekman, F.; Miro, J.m.; Medina-Pestana, J.o. (Transplant Infectious Disease, 2018)
Introduction While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV-infection after transplantation through sexual route, the primary mode of transmission in the general population. Methods From two different centers, we report nine new cases of HIV infection in SOT recipients attributed to sexual acquisition: eight cases of kidney-transplant recipients and one heart-transplant recipient. Findings There were nine cases of post-transplant HIV-infection detected among 14 526 transplants performed 1998 to 2015. In 6/9 cases, infection was contracted 5 years after SOT. All but one patient had stable allograft function under immunosuppressive therapy. The main trigger to diagnosis was late CMV disease and sexually transmitted diseases; five patients had CDC-stage 3 HIV infection. In 7/9 patients, virologic response and CD4 recovery were achieved within 3 months after starting antiretroviral therapy (ART). After an average of 3.6 years post diagnosis, 5/9 patients remained alive with well-controlled infection and functioning allograft. Conclusion Sexual acquisition of HIV infection after SOT represents a difficult challenge, as it may occur in any kind of transplant and at any time. The course of infection resembles that of the general population, with life-threatening infectious complications, but good response to ART. Assessment of lifestyle and risk behavior is paramount, as indications may be not disclosed without direct questioning.
Keywords: HIV infection; antiretroviral therapy; graft survival; heart transplantation; kidney transplantation; patient survival; sexually transmitted disease

Toxoplasmosis in the non-orthotopic heart transplant recipient population, how common is it? Any indication for prophylaxis? - Dhakal, Reshika; Gajurel, Kiran; Montoya, Jose G. (Current Opinion in Organ Transplantation, 2018)
Toxoplasma disease in non-OHT predominantly occurs in pretransplant seronegative recipients- mostly in Dþ/R- group and is rare in seropositive recipients. Posttransplant prophylaxis should be targeted against the high-risk Dþ/R- group and should be considered in seropositive recipients in whom unusually high immunosuppression is implemented. Toxoplasma serologies and PCR should be used in combination for the diagnosis of toxoplasmosis in non-OHT patients.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4) - Drgona, L.; Gudiol, C.; Lanini, S.; Salzberger, B.; Ippolito, G.; Mikulska, M. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety proﬁle of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: The risk and spectrum of infections in patients receiving CD22-targeted agents (i.e. inotuzumab ozogamicin) are similar to those observed with anti-CD20 antibodies. Anti-Pneumocystis prophylaxis and monitoring for cytomegalovirus (CMV) infection is recommended for patients receiving CD30-targeted agents (brentuximab vedotin). Due to the scarcity of data, the risk posed by CD33-targeted agents (gemtuzumab ozogamicin) cannot be assessed. Patients receiving CD38-targeted agents (i.e. daratumumab) face an increased risk of varicella-zoster virus (VZV) infection. Therapy with CD40-targeted agents (lucatumumab or dacetuzumab) is associated with opportunistic infections similar to those observed in hyper-IgM syndrome, and prevention strategies (including anti-Pneumocystis prophylaxis and pre-emptive therapy for CMV infection) are warranted. SLAMF-7 (CD319)-targeted agents (elotuzumab) induce lymphopenia and increase the risk of infection (particularly due to VZV). The impact of CCR4-targeted agents (mogamulizumab) on infection susceptibility is difﬁcult to distinguish from the effect of underlying diseases and concomitant therapies. However, anti-Pneumocystis and antiherpesvirus prophylaxis and screening for chronic hepatitis B virus (HBV) infection are recommended. Implications: Speciﬁc management strategies should be put in place to reduce the risk and/or the severity of infectious complications associated to the reviewed agents. L. Drgona, Clin Microbiol Infect 2018;24:S83 © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction) - Fernández-Ruiz, M.; Meije, Y.; Manuel, O.; Akan, H.; Carratalà, J.; Aguado, J.M.; Delaloye, J. (Clinical Microbiology and Infection, 2018)
Background: The ﬁeld of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians.

Reactivation of Chagas disease among heart transplant recipients in the United States, 2012-2016 - Gray, Elizabeth B.; Hoz, Ricardo M. La; Green, Jaime S.; Vikram, Holenarasipur R.; Benedict, Theresa; Rivera, Hilda; Montgomery, Susan P. (Transplant Infectious Disease, 2018)
Background Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non-endemic countries. Methods We present our experience with 31 patients with chronic Chagas disease who underwent orthotopic heart transplantation in the United States from 2012 to 2016. Patients were monitored following a standard schedule. Results Of the 31 patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a majority (95%) were identified by laboratory monitoring using polymerase chain reaction testing. One patient was identified after the onset of clinical symptoms of reactivation. All subjects with evidence of reactivation were alive at follow-up (median: 60 weeks). Conclusions Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.
Keywords: Chagas disease; Trypanosoma cruzi; heart transplant; reactivation

Outbreaks Associated with Treated Recreational Water — United States, 2000–2014 - Hlavsa, Michele C. (MMWR. Morbidity and Mortality Weekly Report, 2018)
Outbreaks associated with exposure to treated recreational water can be caused by pathogens or chemicals in venues such as pools, hot tubs/spas, and interactive water play venues (i.e., water ...

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52) - Mikulska, M.; Lanini, S.; Gudiol, C.; Drgona, L.; Ippolito, G.; Fernández-Ruiz, M.; Salzberger, B. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety proﬁle of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: Although CD19-targeted agents (blinatumomab or inebilizumab) are not associated with an increased risk of infection, they may cause IgG hypogammaglobulinaemia and neutropenia. The requirement for prolonged intravenous infusion of blinatumomab may increase the risk of catheterassociated bloodstream infections. Infection remains the most common non-haematological adverse effect of anti-CD20 monoclonal antibodies, including severe respiratory tract infection, hepatitis B virus (HBV) reactivation and varicella-zoster virus infection. Screening for chronic or resolved HBV infection is recommended for patients receiving anti-CD20 monoclonal antibodies. Antiviral prophylaxis should be offered for 12e18 months to hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/antihepatitis B core antibody (HBc)-positive patients. Anti-Pneumocystis prophylaxis should be considered in patients receiving concomitant chemotherapy, particularly steroids. Alemtuzumab (anti-CD52) increases the risk of infections, in particular among leukaemia and solid organ transplant patients. These populations beneﬁt from anti-Pneumocystis prophylaxis, prevention strategies for cytomegalovirus infection, and screening for HBV, hepatitis C virus and tuberculosis. Antiviral prophylaxis for at least 6e12 months should be provided for HBsAg-positive patients.

Chapter 3: Left Ventricular Assist Device Infections: A Practical Approach - Muggia, Victoria A.; Minamoto, Grace Y.; Forest, Stephen J.; Lerman, Dana T.; Puius, Yoram A. (Ventricular Assist Devices, 2018)
Left ventricular assist devices (LVADs) have become a standard treatment modality for the management of end-stage heart failure, either as a bridge to cardiac transplantation or as destination therapy. Infection is a frequent complication in up to one-third of LVAD recipients. Although the epidemiology of LVAD infections has been well-described, strategies for prevention, diagnosis, and management of these infectious complications remain controversial and vary among institutions. The goals of this review are to provide the infectious diseases practitioner with a brief introduction to the general anatomy and physiology of an LVAD, pre-implantation infectious disease management guidance, and an understanding of the epidemiology and pathophysiology of LVAD infections. We address methods for the diagnosis and characterization of these infections and suggest medical and surgical approaches for management

Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort - Neofytos, Dionysios; Hirzel, Cedric; Boely, Elsa; Lecompte, Thanh; Khanna, Nina; Mueller, Nicolas J.; Boggian, Katia; Cusini, Alexia; Manuel, Oriol; Delden, Christian van (Transplant Infectious Disease, 2018)
Background Descriptive data on Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients (SOTr) in the era of routine Pneumocystis-prophylaxis are lacking. Methods All adult SOTr between 2008 and 2016 were included. PJP was diagnosed based on consensus guidelines. Early-onset PJP was defined as PJP within the first-year-post-transplant. Results 41/2842 SOTr (1.4%) developed PJP (incidence rate: 0.01/1000 person-days) at a mean of 493-days post-transplant: 21 (51.2%) early vs 20 (48.8%) late-onset PJP. 2465 (86.7%) SOTr received Pneumocystis-prophylaxis for a mean 316 days. PJP incidence was 0.001% and 0.003% (log-rank < 0.001) in SOTr with and without Pneumocystis-prophylaxis, respectively. PJP was an early event in 10/12 (83.3%) SOTr who did not receive Pneumocystis-prophylaxis and developed PJP, compared to those patients who received prophylaxis (11/29, 37.9%; P-value: 0.008). Among late-onset PJP patients, most cases (13/20, 65%) were observed during the 2nd year post-transplant. Age ≥65 years (OR: 2.4, P-value: 0.03) and CMV infection during the first 6 months post-SOT (OR: 2.5, P-value: 0.006) were significant PJP predictors, while Pneumocystis-prophylaxis was protective for PJP (OR: 0.3, P-value: 0.006) in the overall population. Most patients (35, 85.4%) were treated with trimethoprim-sulfamethoxazole for a mean 20.6 days. 1-year mortality was 14.6%. Conclusions In the Pneumocystis-prophylaxis-era, PJP remains a rare post-transplant complication. Most cases occurred post-PJP-prophylaxis-discontinuation, particularly during the second-year-post-transplant. Additional research may help identify indications for Pneumocystis-prophylaxis prolongation.
Keywords: Epidemiology; Pneumocystis jirovecii pneumonia; Solid organ transplant recipients

Screening Coccidioides serology in kidney transplant recipients: A 10-year cross-sectional analysis - Phonphok, Korntip; Beaird, Omer; Duong, Tin; Datta, Nakul; Schaenman, Joanna; Bunnapradist, Suphamai (Transplant Infectious Disease, 2018)
Background Kidney transplant recipients (KTRs) are at risk for reactivation and complicated infection due to Coccidioides. Pre-transplant serological screening should provide benefit for patients from endemic areas. We evaluated Coccidioides seroprevalence by area of residence in KTRs at a major transplant program in Los Angeles. Methods We performed cross-sectional analyses of adult KTRs who underwent transplantation at UCLA between 2007-2016. Patients with Coccidioides serology by enzyme immunoassay (EIA) before or within 14 days from transplantation were included. Patients were classified as living in highly, established, suspected, or not endemic areas by their residential zip code. Results Overall prevalence of Coccidioides IgG and IgM were 1.4% and 2.8%, respectively. Of patients with positive serology, 31.4% had isolated IgG and 66.3% isolated IgM. Patients from established and highly endemic areas had IgG seropositivity of 3.7% versus 1.3% for patients living in suspected endemic areas(P < .01). Rates of IgM seropositivity were 3.7% compared to 2.8% respectively (P = .28). No patients from non-endemic areas had positive screening serology. Conclusions Pre-transplant serological screening for Coccidioides is recommended in kidney transplant candidates from endemic areas. We observed high seroprevalence among patients from highly and established endemic areas, for whom universal prophylaxis is recommended. For residents from less well-established areas of endemicity, serological screening showed benefit in identifying patients at risk. In patients with isolated EIA IgM, performing repeat and confirmatory tests is recommended. Patients from non-endemic areas had low risk of infection, however, a thorough social history is necessary to evaluate risk.
Keywords: CoccidioidesEIA; endemic areas; kidney transplant; screening Coccidioides

Chagas Disease Recommendations for Solid-Organ Transplant Recipients and Donors - Pierrotti, Lígia Camera; Carvalho, Noemia Barbosa; Amorin, Jimena Prieto; Pascual, Julio; Kotton, Camille N.; López-Vélez, Rogelio (Transplantation, 2018)

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors) - Redelman-Sidi, G.; Michielin, O.; Cervera, C.; Ribi, C.; Aguado, J.M.; Fernández-Ruiz, M.; Manuel, O. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors) - Reinwald, M.; Silva, J.T.; Mueller, N.J.; Fortún, J.; Garzoni, C.; de Fijter, J.W.; Fernández-Ruiz, M.; Grossi, P.; Aguado, J.M. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies.

Chikungunya in solid organ transplant recipients, a case series and literature review - Rosso, Fernando; Rodríguez, Sarita; Cedano, Jorge A.; Mora, Barbara L.; Moncada, Pablo A.; Velez, Juan D. (Transplant Infectious Disease, 2018)
Chikungunya virus is a recent emerging arbovirus in Latin America, and the clinical manifestations can vary from fever and rash to severe chronic inflammatory arthritis. Few reports have been published regarding this infection in immunocompromised patients, including solid organ transplant recipients. We report a case series of solid organ transplant recipients with confirmed Chikungunya infection by positive reverse transcription polymerase chain reaction (RT-PCR), identified between January 2014 and December 2016. In addition, we conducted a literature review searching PubMed, EMBASE, and LILACS databases on Chikungunya infection in solid organ transplant recipients. Ten solid organ transplant recipients were included, consisting of 5 kidney, 4 liver, and 1 liver/kidney transplant recipient. Mean age of the transplant recipients was 47 years, and the most frequent symptoms of Chikungunya infection were arthralgia and fever. None of the patients required treatment in the intensive care unit, no deaths or graft rejection occurred. None of our patients had recurrent arthritis during 3-month follow-up period after the infection. Twenty-one cases of Chikungunya virus were identified in the literature review. Most cases had a benign clinical course with no severe complications, death, or chronic inflammatory arthritis. In conclusion, Chikungunya infection in solid organ transplant recipients has a benign course and has no chronic recurrent arthritis. It is possible that the immunosuppression regimen could decrease the risk of severe or chronic inflammatory manifestations in solid organ transplant recipients infected with Chikungunya.
Keywords: Chikungunya; infection; solid organ transplant; transplant recipients

Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients - Sparkes, Tracy; Manitpisitkul, Wana; Masters, Brian; Bartlett, Stephen T.; Davis, Charles; Husson, Jennifer; Amoroso, Anthony; Haririan, Abdolreza (Transplant Infectious Disease, 2018)
Background Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. Methods In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. Results Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. Conclusions Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.
Keywords: HIV; antiretroviral; renal transplantation

Training in transplant infectious diseases: A survey of infectious diseases and transplant infectious diseases fellows in the United States and Canada - Tan, Susanna K.; Theodoropoulos, Nicole; La Hoz, Ricardo M.; Mossad, Sherif B.; Kotton, Camille N.; Danziger-Isakov, Lara A.; Kumar, Deepali; Huprikar, Shirish; On behalf of the American Society of Transplantation, Infectious Diseases Community of Practice (Transplant Infectious Disease, 2018)
Background Infectious diseases (ID) specialists with experience in managing infections in transplant recipients and other immunocompromised hosts are increasingly needed as these fields expand. Methods To evaluate experiences and identify trainee-described needs in transplant infectious diseases (TID) training, the American Society of Transplantation, Infectious Diseases Community of Practice (AST IDCOP) surveyed ID fellows across the United States and TID fellows in the United States and Canada and received responses from 203 ID fellows and 13 TID fellows. Results Among ID fellows, the amount of TID training during ID fellowship was rated between less than ideal and adequate. Reasons cited included limited frequency of didactic activities and limited exposure to transplant patients during training. In particular, ID fellows at low-volume transplantation centers expressed interest in more TID training time, away training opportunities, and specific TID didactics. Educational resources of high interest among trainees were case-based interactive websites, mobile phone applications with TID guidelines, and a centralized collection of relevant articles. Pediatric ID fellows reported lower satisfaction scores with TID training, while TID fellows were overall satisfied or more than satisfied with their training experience. Conclusion Findings from this survey will inform local and national TID educational initiatives.
Keywords: educational; survey; trainee; transplant infectious diseases

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline - Ullmann, A.J.; Aguado, J.M.; Arikan-Akdagli, S.; Denning, D.W.; Groll, A.H.; Lagrou, K.; Lass-Flörl, C.; Lewis, R.E.; Munoz, P.; Verweij, P.E.; Warris, A.; Ader, F.; et al. (Clinical Microbiology and Infection, 2018)
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identiﬁcation to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for ﬁrst-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in highrisk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging. A.J. Ullmann, Clin Microbiol Infect 2018;24:1 © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients - Urbancic, Karen F.; Pisasale, Daisy; Wight, Joel; Trubiano, Jason A. (Transplant Infectious Disease, 2018)
Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.
Keywords: Pneumocystis jirovecii pneumonia; adverse drug reactions; dapsone; hematopoietic stem cell transplantation

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors) - Winthrop, K.L.; Mariette, X.; Silva, J.T.; Benamu, E.; Calabrese, L.H.; Dumusc, A.; Smolen, J.S.; Aguado, J.M.; Fernández-Ruiz, M. (Clinical Microbiology and Infection, 2018)
Background: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. Aims: To review, from an Infectious Diseases perspective, the safety proﬁle of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Sources: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Content: Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5targeted (mepolizumab) agents have a moderate risk of infection and no speciﬁc prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-a agents. IL-12/23targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pretreatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2e4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection.

Antifungal Susceptibility of Emerging Dimorphic Pathogens in the Family Ajellomycetaceae - Dukik, Karolina; Al-Hatmi, Abdullah M. S.; Curfs-Breuker, Ilse; Faro, Dirk; de Hoog, Sybren; Meis, Jacques F. (Antimicrobial Agents and Chemotherapy, 2017)
The in vitro susceptibilities of 24 molecularly identified dimorphic fungi belonging to the genera Adiaspiromyces, Blastomyces, and Emergomyces within the family Ajellomycetaceae were tested against 8 standard antifungal agents using CLSI document M38-A2. Amphotericin B and posaconazole had the lowest geometric mean MICs (<0.05 μg/ml) followed by itraconazole (<0.07 μg/ml), voriconazole (<0.15 μg/ml), and isavuconazole (<0.42 μg/ml) while fluconazole was not active. Micafungin demonstrated good in vitro antifungal activity against Emergomyces (geometric mean minimum effective concentration [GM MEC] 0.1 μg/ml) and Blastomyces (GM MEC <0.017 μg/ml).

Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation - Marty, Francisco M.; Ljungman, Per; Chemaly, Roy F.; Maertens, Johan; Dadwal, Sanjeet S.; Duarte, Rafael F.; Haider, Shariq; Ullmann, Andrew J.; Katayama, Yuta; Brown, Janice; Mullane, Kathleen M.; Boeckh, Michael; et al. (New England Journal of Medicine, 2017)
CMV infection is a common complication in patients undergoing hematopoietic-cell transplantation. The incidence of CMV infection was 23 percentage points lower with prophylactic letermovir, a CMV–terminase complex inhibitor, than with placebo, with only low-level toxic effects.

Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial - Aguilar-Guisado, Manuela; Espigado, Ildefonso; Martín-Peña, Almudena; Gudiol, Carlota; Royo-Cebrecos, Cristina; Falantes, José; Vázquez-López, Lourdes; Montero, María Isabel; Rosso-Fernández, Clara; Martino, María de la Luz; Parody, Rocío; González-Campos, José; et al. (The Lancet Haematology, 2017)
Summary Background Continuation of empirical antimicrobial therapy (EAT) for febrile neutropenia in patients with haematological malignancies until neutrophil recovery could prolong the therapy unnecessarily. We aimed to establish whether EAT discontinuation driven by a clinical approach regardless of neutrophil recovery would optimise the duration of therapy. Methods We did an investigator-driven, superiority, open-label, randomised, controlled phase 4 clinical trial in six academic hospitals in Spain. Eligible patients were adults with haematological malignancies or haemopoietic stem-cell transplantation recipients, with high-risk febrile neutropenia without aetiological diagnosis. An independent, computer-generated randomisation sequence was used to randomly enrol patients (1:1) to the experimental or control group. Investigators were masked to assignment only before randomisation. EAT based on an antipseudomonal β-lactam drug as monotherapy (ceftazidime or cefepime, meropenem or imipenem, or piperacillin-tazobactam) or as combination therapy (with an aminoglycoside, fluoroquinolone, or glycopeptide) was started according to local protocols and following international guidelines and recommendations. For the experimental group, EAT was withdrawn after 72 h or more of apyrexia plus clinical recovery; for the control group, treatment was withdrawn when the neutrophil count was also 0·5 × 109 cells per L or higher. The primary efficacy endpoint was the number of EAT-free days. Primary analyses were done in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01581333. Findings Between April 10, 2012, and May 31, 2016, 157 episodes among 709 patients assessed for eligibility were included in analyses. 78 patients were randomly assigned to the experimental group and 79 to the control group. The mean number of EAT-free days was significantly higher in the experimental group than in the control group (16·1 [SD 6·3] vs 13·6 [7·2], absolute difference −2·4 [95% CI −4·6 to −0·3]; p=0·026). 636 adverse events were reported (341 in the experimental group vs 295 in the control group; p=0·057) and most (580 [91%]; 323 in the experimental group vs 257 in the control group) were considered mild or moderate (grade 1–2). The most common adverse events in the experimental versus the control group were mucositis (28 [36%] of 78 patients vs 20 [25%] of 79 patients), diarrhoea (23 [29%] of 78 vs 24 [30%] of 79), and nausea and vomiting (20 [26%] of 78 vs 22 [28%] of 79). 56 severe adverse events were reported, 18 in the experimental group and 38 in the control group. One patient died in the experimental group (from hepatic veno-occlusive disease after an allogeneic haemopoietic stem-cell transplantation) and three died in the control group (one from multiorgan failure, one from invasive pulmonary aspergillosis, and one from a post-chemotherapy intestinal perforation). Interpretation In high-risk patients with haematological malignancies and febrile neutropenia, EAT can be discontinued after 72 h of apyrexia and clinical recovery irrespective of their neutrophil count. This clinical approach reduces unnecessary exposure to antimicrobials and it is safe. Funding Instituto de Salud Carlos III, Spanish Ministry of Economy (PI11/02674).

2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction - Kusumoto, Fred M.; Schoenfeld, Mark H.; Wilkoff, Bruce L.; Berul, Charles I.; Birgersdotter-Green, Ulrika M.; Carrillo, Roger; Cha, Yong-Mei; Clancy, Jude; Deharo, Jean-Claude; Ellenbogen, Kenneth A.; Exner, Derek; Hussein, Ayman A.; et al. (Heart Rhythm, 2017)
Document Reviewers: Adrian M. Baranchuk, MD, FACC, FRCPC, FCCS; Carina Blomström-Lundqvist, MD, PhD; Frank A. Fish, MD; James M. Horton, MD; Roberto Keegan, MD; Miguel A. Leal, MD, FACC, FHRS; Nigel Lever, MBChB, FRACP; Aman Mahajan, MD, PhD, MBA; Marc R. Moon, MD; Siva K. Mulpuru, BS, MB, MBBS, MD, FHRS, CCDS

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea - Shane, Andi L.; Mody, Rajal K.; Crump, John A.; Tarr, Phillip I.; Steiner, Theodore S.; Kotloff, Karen; Langley, Joanne M.; Wanke, Christine; Warren, Cirle Alcantara; Cheng, Allen C.; Cantey, Joseph; Pickering, Larry K. (Clinical Infectious Diseases, 2017)
Abstract. These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. T

A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection - Kosaka, Makoto; Ushiki, Atsuhito; Ikuyama, Yuichi; Hirai, Kazuya; Matsuo, Akemi; Hachiya, Tsutomu; Hanaoka, Masayuki (Antimicrobial Agents and Chemotherapy, 2017)
The dose of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) infection has not been verified. The aim of this study was to investigate the efficacy and toxicity of a low-dose TMP-SMX regimen in such patients. A retrospective study was conducted in four hospitals. We reviewed the medical records of patients with PCP but not HIV (non-HIV-PCP) who were treated with TMP-SMX between 2003 and 2016. The patients were divided into conventional-dose (TMP, 15 to 20 mg/kg/day) and low-dose (TMP, <15 mg/kg/day) groups after patients who received high-dose (TMP, >20 mg/kg/day) treatment were excluded. Grouping was done according to a correction dose, which was based on renal function. Eighty-two patients had non-HIV-PCP. The numbers of patients who received high-, conventional-, and low-dose treatments were 5, 36, and 41, respectively. Kaplan-Meier analysis for death associated with PCP showed no statistically significant difference in survival rates between the conventional- and low-dose groups. Ninety-day cause-specific mortality rates were 25.0% and 19.5% in the conventional-dose and low-dose groups (P = 0.76), respectively. Adverse events that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events (version 4.0) (National Cancer Institute, 2010) were 41.7% and 17.1% in the conventional-dose and low-dose groups (P = 0.02), respectively. Moreover, vomiting (P = 0.03) and a decrease in platelet count (P = 0.03) occurred more frequently in the conventional-dose group. Treatment of non-HIV-PCP with low-dose or conventional-dose TMP-SMX produces comparable survival rates; however, the low-dose regimen is better tolerated and associated with fewer adverse effects.

Chikungunya Infection in Solid Organ Transplant Recipients - Girão, E. S.; Rodrigues dos Santos, B. G.; do Amaral, E. S.; Costa, P. E. G.; Pereira, K. B.; de Araujo Filho, A. H.; Hyppolito, E. B.; Mota, M. U.; Marques, L. C. B. F.; Costa de Oliveira, C. M.; da Silva, S. L.; Garcia, J. H. P.; et al. (Transplantation Proceedings, 2017)
Background Chikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients. Methods We retrospectively evaluated 13 cases of CHIKV infection in SOT recipients between January 2016 and December 2016 confirmed by laboratory tests and transplanted in the Renal and Liver Transplant Units of Walter Cantídio University Hospital from Federal University of Ceará. Results Positive CHIKV serology (enzyme-linked immunosorbent assay immunoglobulin M) was found in all patients (9 kidney and 4 liver transplant recipients). All of these patients had been living in endemic areas for dengue and CHIKV in the past months before the illness. The mean time between transplantation and CHIKV infection was of 7.2 years. Fever presented in 11 (84.6%) patients and 5 (38.5%) presented with a maculopapular rash. All cases had joint symptoms: 11 (84.6%) with symmetrical and peripheral polyarthralgia/polyarthritis and 2 (15.3%) with monoarthralgia/monoarthritis. Six (46%) patients had a joint complaint that lasted 3 months. Two patients had concomitant positive dengue serology (enzyme-linked immunosorbent assay immunoglobulin M). There were no cases of complications or deaths. Conclusion SOT with CHIKV infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no apparent damage to the graft.

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) - Haworth, Charles S.; Banks, John; Capstick, Toby; Fisher, Andrew J.; Gorsuch, Thomas; Laurenson, Ian F.; Leitch, Andrew; Loebinger, Michael R.; Milburn, Heather J.; Nightingale, Mark; Ormerod, Peter; Shingadia, Delane; et al. (Thorax, 2017)
Section 4: What is the evidence for transmission of NTM between individuals? Recommendation Section 5: How should the lung disease attributable to NTM infection be defined? Recommendation Good practice point Section 6: What samples should be used to detect pulmonary non-tuberculous mycobacterial infection? Recommendations Good practice points Section …

Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation - Tzannou, Ifigeneia; Papadopoulou, Anastasia; Naik, Swati; Leung, Kathryn; Martinez, Caridad A.; Ramos, Carlos A.; Carrum, George; Sasa, Ghadir; Lulla, Premal; Watanabe, Ayumi; Kuvalekar, Manik; Gee, Adrian P.; et al. (Journal of Clinical Oncology, 2017)
Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.

Marijuana Use and Organ Transplantation: a Review and Implications for Clinical Practice - Rai, Harinder Singh; Winder, Gerald Scott (Current Psychiatry Reports, 2017)
PURPOSE OF REVIEW: Physicians of all disciplines must rapidly adjust their clinical practices following the expansion of marijuana legalization across the country. Organ transplantation teams are uniquely struggling in this gray zone with eight states having passed laws explicitly banning the denial of transplant listing based on a patient's use of medical marijuana. In this review, we examine the clinical evidence of marijuana use in transplant patients to enable psychiatric providers to meaningfully contribute to the relevant medical and psychiatric aspects of this issue in a unique patient population. RECENT FINDINGS: There is no consensus among experts regarding marijuana use in transplantation patients. There are extant case reports of post-transplant complications attributed to marijuana use including membranous glomerulonephritis, ventricular tachycardia, and tacrolimus toxicity. However, recent studies suggest that the overall survival rates in kidney, liver, lung, and heart transplant patients using marijuana are equivalent to non-users. Transplant teams should not de facto exclude marijuana users from transplant listing but instead holistically evaluate a patient's candidacy, integrating meaningful medical, psychiatric, and social variables into the complex decision-making process. Psychiatric providers can play a key role in this process. Appropriate stewardship over donor organs, a limited and precious resource, will require a balance of high-clinical standards with inclusive efforts to treat as many patients as possible.
Keywords: Attitude of Health Personnel; Cannabis; Clinical Decision-Making; Humans; Legalization; Marijuana; Marijuana Use; Organ Transplantation; Organ transplantation; Patient Selection; Postoperative Complications; Psychiatry; Transplant psychiatry; Transplantation

Donor-Derived Mycoplasma hominis and an Apparent Cluster of M. hominis Cases in Solid Organ Transplant Recipients - Smibert, Olivia C; Wilson, Heather L; Sohail, Asma; Narayanasamy, Shanti; Schultz, Mark B; Ballard, Susan A; Kwong, Jason C; de Boer, Jim; Morrissey, C Orla; Peleg, Anton Y; Snell, Greg I; Paraskeva, Miranda A; et al. (Clinical Infectious Diseases, 2017)
Invasive and disseminated Mycoplasma hominis infections are well recognized but uncommon complications in solid organ transplant recipients. In a single center, a cluster of M. hominis infections were identified in lung transplant recipients from the same thoracic intensive care unit (ICU). We sought to determine the source(s) of these infections.Medical records of the donor and infected transplant recipients were reviewed for clinical characteristics. Clinical specimens underwent routine processing with subculture on Mycoplasma-specific Hayflick agar. Mycoplasma hominis identification was confirmed using sequencing of the 16S ribosomal RNA gene. Mycoplasma hominis isolates were subjected to whole-genome sequencing on the Illumina NextSeq platform.Three lung transplant recipients presented with invasive M. hominis infections at multiple sites characterized by purulent infections without organisms detected by Gram staining. Each patient had a separate donor; however, pretransplant bronchoalveolar lavage fluid was only available from the donor for patient 1, which subsequently grew M. hominis. Phylo- and pangenomic analyses indicated that the isolates from the donor and the corresponding recipient (patient 1) were closely related and formed a distinct single clade. In contrast, isolates from patients 2 and 3 were unrelated and divergent from one another.Mycoplasma hominis should be considered a cause of donor-derived infection. Genomic data suggest donor-to-recipient transmission of M. hominis. Additional patients co-located in the ICU were found to have genetically unrelated M. hominis isolates, excluding patient-to-patient transmission.

An ISHLT consensus document for prevention and management strategies for mechanical circulatory support infection - Kusne, Shimon; Mooney, Martha; Danziger-Isakov, Lara; Kaan, Annemarie; Lund, Lars H.; Lyster, Haifa; Wieselthaler, Georg; Aslam, Saima; Cagliostro, Barbara; Chen, Jonathan; Combs, Pamela; Cochrane, Adam; et al. (The Journal of Heart and Lung Transplantation, 2017)

Left ventricular assist device-related infections: a multicentric study - Siméon, S.; Flécher, E.; Revest, M.; Niculescu, M.; Roussel, J.-C.; Michel, M.; Leprince, P.; Tattevin, P. (Clinical Microbiology and Infection, 2017)
Abstract Objectives The implantable left ventricular assist device (LVAD) is a major therapeutic development for end-stage heart failure in selected patients. As their use is expanding, infectious complications are emerging, with limited data available to guide their management. We aimed to better characterize LVAD-related infections. Methods We enrolled all consecutive patients diagnosed with LVAD-related infections in three referral centres in France, using a standardized definition of infections in patients with LVAD. Data were collected from medical charts using a standardized questionnaire. Results Between 2007 and 2012, 159 patients received LVAD for end-stage heart failure. Among them, 36 (22.6%; 5 women, 31 men) presented at least one infectious complication, after a median time of 2.9 months from LVAD implantation (interquartile range, 1.8–7.5), with a median follow up of 12 months (interquartile range 8–17). Main co-morbidities were alcoholism (33%), diabetes (11%) and immunosuppression (11%). Mean age at implantation was 51 (±11) years. LVAD were implanted as bridge-to-transplantation (n=22), bridge-to-recovery (n=8), destination therapy (n=4), or unspecified (n=2). LVAD-related infections were restricted to the driveline exit site (n=17), had loco-regional extension (n=13), or reached the internal pump (n=3). The main bacteria isolated were Staphylococcus aureus (n=20), coagulase-negative staphylococci (n=7), Enterobacteriaceae (n=14), Pseudomonas aeruginosa (n=10) and Corynebacterium sp. (n=7), with polymicrobial infections in 19 cases. LVAD could be retained in all patients, with the use of prolonged antibacterial treatment in 34 (94%), and debridement in 17 (47%). One patient died due to LVAD-associated infection. Conclusions LVAD-related infections are common after LVAD implantation, and may be controlled by prolonged antibiotic treatment.

Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children - Huppler, Anna R; Fisher, Brian T; Lehrnbecher, Thomas; Walsh, Thomas J; Steinbach, William J (Journal of the Pediatric Infectious Diseases Society, 2017)
Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published literature and contemporary strategies for using the biomarkers galactomannan, (1→3)-β-d-glucan, Candida mannan antigen and anti-mannan antibody, and fungal polymerase chain reaction for diagnosing invasive fungal disease in children. Data on biomarker use in neonates and children with cancer, history of hematopoietic stem cell transplant, or primary immunodeficiency are included. Fungal biomarker tests performed on blood, other body fluids, or tissue specimens represent promising adjuncts to the diagnostic armamentarium in populations with a high prevalence of invasive fungal disease, but substantial gaps exist in the correct use and interpretation of these diagnostic tools in pediatric patients.

HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B - Collin, Vanessa; Flamand, Louis (Viruses, 2017)
Unlike other human herpesviruses, human herpesvirus 6A and 6B (HHV-6A/B) infection can lead to integration of the viral genome in human chromosomes. When integration occurs in germinal cells, the integrated HHV-6A/B genome can be transmitted to 50% of descendants. Such individuals, carrying one copy of the HHV-6A/B genome in every cell, are referred to as having inherited chromosomally-integrated HHV-6A/B (iciHHV-6) and represent approximately 1% of the world’s population. Interestingly, HHV-6A/B integrate their genomes in a specific region of the chromosomes known as telomeres. Telomeres are located at chromosomes’ ends and play essential roles in chromosomal stability and the long-term proliferative potential of cells. Considering that the integrated HHV-6A/B genome is mostly intact without any gross rearrangements or deletions, integration is likely used for viral maintenance into host cells. Knowing the roles played by telomeres in cellular homeostasis, viral integration in such structure is not likely to be without consequences. At present, the mechanisms and factors involved in HHV-6A/B integration remain poorly defined. In this review, we detail the potential biological and medical impacts of HHV-6A/B integration as well as the possible chromosomal integration and viral excision processes.
Keywords: human herpesvirus 6A/B; inherited chromosomally-integrated HHV-6A/B; integration; reactivation; telomere

The value of fluorine-18 deoxyglucose positron emission tomography scans in patients with ventricular assist device specific infections† - Bernhardt, Alexander M; Pamirsad, Mustafa A; Brand, Chantal; Reichart, Daniel; Tienken, Milena; Barten, Markus J; Schaefer, Andreas; Grahn, Hanno; Rybczynski, Meike; Deuse, Tobias; Reichenspurner, Hermann; Wagner, Florian M. (European Journal of Cardio-Thoracic Surgery, 2017)
BACKGROUND: Infections are major complications in patients with ventricular assist devices (VAD). Positron emission tomography with deoxyglucose marked by fluorine-18 (18F-FDG PET/CT) is a diagnostic tool to scan for tissue with high metabolism as present in infections. The specificity of 18F-FDG PET/CT to discriminate between infection and an aseptic reaction of the implanted device is not defined and its evaluation is the aim of this retrospective analysis.METHODS: Until September 2015 a total of 100 patients underwent VAD implantations in our institution. Twenty-one patients (mean age 53.7 ± 14.3 years) had 29 PET-CT examinations for a suspected infection. All radiology reports were compared to clinical and intraoperative parameters. Infections were reported according to the guidelines of the International Society of Heart and Lung Transplantation. Follow-up was 222 days (range 107–484 days) after PET-CT scans and was complete in all patients.RESULTS: In 7 patients PET-CT scan ruled out any VAD associated infection. Sixteen patients had a VAD specific infection. Two patients had false negative PET-CT scan results. The sensitivity of VAD-specific infections was 87.5%, the specificity 100%, the positive predictive value was 100% and the negative predictive value 86.7%. Seven patients had more than one PET-CT scans at different time points.CONCLUSIONS: PET-CT scan findings showed a high specificity and positive predictive value for VAD-specific infections. Therefore, it may have the potential to guide the clinician in handling patients with infectious complications after VAD implantation.

Candida auris candidaemia in Indian ICUs: analysis of risk factors - Rudramurthy, Shivaprakash M.; Chakrabarti, Arunaloke; Paul, Raees A.; Sood, Prashant; Kaur, Harsimran; Capoor, Malini R.; Kindo, Anupma J.; Marak, Rungmei S. K.; Arora, Anita; Sardana, Raman; Das, Shukla; Chhina, Deepinder; et al. (The Journal of Antimicrobial Chemotherapy, 2017)
Objectives: To identify the risk factors associated with Candida auris candidaemia, as this fungus now poses a global threat. Methods: We performed a subgroup analysis of a previously reported study of 27 Indian ICUs. The clinical data of candidaemia cases due to C. auris and other Candida species were compared to determine significant risk factors associated with C. auris infection. Results: Of the 1400 candidaemia cases reported earlier, 74 (5.3%) from 19 of 27 ICUs were due to C. auris . The duration of ICU stay prior to candidaemia diagnosis was significantly longer in patients with C. auris candidaemia (median 25, IQR 12-45 days) compared with the non- auris group (median 15, IQR 9-28, P  <   0.001). Based on logistic regression modelling, admission to north Indian ICUs [OR 2.1 (1.2-3.8); P  =   0.012], public-sector hospital [OR 2.2 (1.2-3.9); P  =   0.006], underlying respiratory illness [OR 2.1 (1.3-3.6); P  =   0.002], vascular surgery [OR 2.3 (1.00-5.36); P  =   0.048], prior antifungal exposure [OR 2.8 (1.6-4.8); P  <   0.001] and low APACHE II score [OR 0.8 (0.8-0.9); P  =   0.007] were significantly associated with C. auris candidaemia. The majority (45/51, 88.2%) of the isolates were clonal. A considerable number of isolates were resistant to fluconazole ( n  =   43, 58.1%), amphotericin B ( n  =   10, 13.5%) and caspofungin ( n  =   7, 9.5%). Conclusions: Although C. auris infection has been observed across India, the number of cases is higher in public-sector hospitals in the north of the country. Longer stay in ICU, underlying respiratory illness, vascular surgery, medical intervention and antifungal exposure are the major risk factors for acquiring C. auris infection even among patients showing lower levels of morbidity.
Keywords: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; Echinocandins; Female; Fluconazole; Humans; India; Intensive Care Units; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Mycological Typing Techniques; Risk Factors; Young Adult

Laboratory Diagnostics for Histoplasmosis - Azar, Marwan M.; Hage, Chadi A. (Journal of Clinical Microbiology, 2017)
The diagnosis of histoplasmosis is based on a multifaceted approach that includes clinical, radiographic, and laboratory evidence of disease. The gold standards for laboratory diagnosis include demonstration of yeast on pathological examination of tissue and isolation of the mold in the culture of clinical specimens; however, antigen detection has provided a rapid, noninvasive, and highly sensitive method for diagnosis and is a useful marker of treatment response. Molecular methods with improved sensitivity on clinical specimens are being developed but are not yet ready for widespread clinical use. This review synthesizes currently available laboratory diagnostics for histoplasmosis, with an emphasis on complexities of testing and performance in various clinical contexts.

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia - Boeckh, Michael; Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; et al. (The Journal of Infectious Diseases, 2017)
Background. Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. Methods. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR. Results. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. Conclusion. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding.

Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses - Lockhart, Shawn R.; Etienne, Kizee A.; Vallabhaneni, Snigdha; Farooqi, Joveria; Chowdhary, Anuradha; Govender, Nelesh P.; Colombo, Arnaldo Lopes; Calvo, Belinda; Cuomo, Christina A.; Desjardins, Christopher A.; Berkow, Elizabeth L.; Castanheira, Mariana; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2017)
Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Infection in Organ Transplantation - Fishman, J. A. (American Journal of Transplantation, 2017)

Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety - Irwin, Linda; Kotton, Camille N.; Elias, Nahel; Palafox, Julie; Basler, Debra; Shao, Sarah H.; Lester, William; Zhang, Xiaofeng; Kimball, Brendan; Trencher, Carrie; Fishman, Jay A. (Transplant Infectious Disease, 2017)
The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at “high risk” (Centers for Disease Control and Prevention, CDC 1994) or “increased risk” (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single-center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased-risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post-transplant HBV core serologies reverted to negative on re-testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre- and post-transplant microbiological testing.
Keywords: HIV; donor-derived infection; hepatitis B virus; hepatitis C virus; increased risk; nucleic acid testing; serologic assays

Purpureocillium lilacinum tattoo-related skin infection in a kidney transplant recipient - Trinh, Sonya A.; Angarone, Michael P. (Transplant Infectious Disease, 2017)
Purpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo-related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18S ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P. lilacinum included violet colonies on malt extract agar, long tapering brush-like phialides, and elliptical conidia attached in chains. P. lilacinum has intrinsic resistance to many antifungal agents including amphotericin B, but voriconazole and posaconazole have good in vitro activity. The patient was treated with voriconazole with subsequent resolution of the papules after 3 months of therapy.
Keywords: Paecilomyces; Purpureocillium; solid organ transplant; tattoo

How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients - El Chaer, Firas; Shah, Dimpy P.; Chemaly, Roy F. (Blood, 2016)
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV.

Galactomannan, β-D-Glucan, and Polymerase Chain Reaction–Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis - Lehrnbecher, Thomas; Robinson, Paula D.; Fisher, Brian T.; Castagnola, Elio; Groll, Andreas H.; Steinbach, William J.; Zaoutis, Theoklis E.; Negeri, Zelalem F.; Beyene, Joseph; Phillips, Bob; Sung, Lillian (Clinical Infectious Diseases, 2016)
We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)–based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase - Oliver, Jason D.; Sibley, Graham E. M.; Beckmann, Nicola; Dobb, Katharine S.; Slater, Martin J.; McEntee, Laura; du Pré, Saskia; Livermore, Joanne; Bromley, Michael J.; Wiederhold, Nathan P.; Hope, William W.; Kennedy, Anthony J.; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2016)
New antifungal drugs that act via novel mechanisms are urgently needed to combat the high mortality of invasive fungal disease and the emergence of resistance to existing therapies. We describe the discovery, structure, activity, and mechanism of action of F901318, a new antifungal agent. A member of a novel class of antifungals, the orotomides, F901318 acts via inhibition of dihydroorotate dehydrogenase, an enzyme of de novo pyrimidine biosynthesis. F901318 is currently in clinical development for the treatment of invasive aspergillosis., There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals.

Molecular characterisation and antifungal susceptibility of clinical Cryptococcus deuterogattii (AFLP6/VGII) isolates from Southern Brazil - Herkert, P. F.; Hagen, F.; de Oliveira Salvador, G. L.; Gomes, R. R.; Ferreira, M. S.; Vicente, V. A.; Muro, M. D.; Pinheiro, R. L.; Meis, J. F.; Queiroz-Telles, F. (European Journal of Clinical Microbiology & Infectious Diseases, 2016)
Cryptococcosis, caused by Cryptococcus gattii sensu lato, is an emerging disease that was initially found in (sub)tropical regions but recently expanded to temperate regions. Cryptococcus gattii s.l. infections are mostly encountered in healthy individuals, frequently affecting both lungs and the central nervous system (CNS). Usually, C. gattii s.l. is less susceptible to antifungal compounds than its counterpart, C. neoformans s.l. We studied 18 clinical C. gattii s.l. isolates with amplified fragment length polymorphism (AFLP) fingerprinting, mating-typing, multi-locus sequence typing (MLST) and antifungal susceptibility testing. All isolates were C. deuterogattii (genotype AFLP6/VGII), 14 were mating-type α and four were type a. Amphotericin B, itraconazole, voriconazole, posaconazole and isavuconazole showed high activity, with minimum inhibitory concentration (MIC) ranges of 0.063–0.25, 0.031–0.25, 0.031–0.25, 0.031–0.25 and <0.016–0.25 μg mL−1, respectively. Fluconazole and flucytosine had high geometric mean MICs of 2.07 and 3.7 μg mL−1, respectively. Most cases occurred in immunocompetent patients (n = 10; 55.6 %) and CNS involvement was the most common clinical presentation (n = 14; 77.8 %). Three patients (16.7 %) showed sequelae, hyperreflexia, dysarthria, diadochokinesia, anosmia and upper limb weakness. In conclusion, all infections were caused by C. deuterogattii (AFLP6/VGII) and the majority of patients were immunocompetent, with the CNS as the most affected site. All antifungal drugs had high in vitro activity against C. deuterogattii isolates, except fluconazole and flucytosine.
Keywords: Amplified Fragment Length Polymorphism Analysis; Amplify Fragment Length Polymorphism; Antifungal Agents; Brazil; Cryptococcosis; Cryptococcus gattii; DNA Fingerprinting; Drug Resistance, Fungal; Female; Fluconazole; Genes, Mating Type, Fungal; Genotype; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Minimum Inhibitory Concentration; Multilocus Sequence Typing; Voriconazole

Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis - Nahid, Payam; Dorman, Susan E.; Alipanah, Narges; Barry, Pennan M.; Brozek, Jan L.; Cattamanchi, Adithya; Chaisson, Lelia H.; Chaisson, Richard E.; Daley, Charles L.; Grzemska, Malgosia; Higashi, Julie M.; Ho, Christine S.; et al. (Clinical Infectious Diseases, 2016)
The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis - Galgiani, John N.; Ampel, Neil M.; Blair, Janis E.; Catanzaro, Antonino; Geertsma, Francesca; Hoover, Susan E.; Johnson, Royce H.; Kusne, Shimon; Lisse, Jeffrey; MacDonald, Joel D.; Meyerson, Shari L.; Raksin, Patricia B.; et al. (Clinical Infectious Diseases, 2016)

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society - Kalil, Andre C.; Metersky, Mark L.; Klompas, Michael; Muscedere, John; Sweeney, Daniel A.; Palmer, Lucy B.; Napolitano, Lena M.; O'Grady, Naomi P.; Bartlett, John G.; Carratalà, Jordi; El Solh, Ali A.; Ewig, Santiago; et al. (Clinical Infectious Diseases, 2016)
Abstract. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended t

ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients - Maertens, Johan; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J. Peter; Alanio, Alexandre; Hauser, Philippe M.; Lagrou, Katrien; Melchers, Willem J. G.; Helweg-Larsen, Jannik; Matos, Olga; Bretagne, Stéphane; et al. (Journal of Antimicrobial Chemotherapy, 2016)
The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2–3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults (A-II) and children (A-I) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen (B-II). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.

ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients - Maschmeyer, Georg; Helweg-Larsen, Jannik; Pagano, Livio; Robin, Christine; Cordonnier, Catherine; Schellongowski, Peter; on behalf of the 6th European Conference on Infections in Leukemia (ECIL-6), a joint venture of The European Group for Blood and Marrow Transplantation (EBMT), The European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and The European LeukemiaNet (ELN) (Journal of Antimicrobial Chemotherapy, 2016)
The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.

Implementation of Molecular Surveillance After a Cluster of Fatal Toxoplasmosis at 2 Neighboring Transplant Centers - Isa, Flonza; Saito, Kohta; Huang, Yao-Ting; Schuetz, Audrey; Babady, N. Esther; Salvatore, Steven; Pessin, Melissa; van Besien, Koen; Perales, Miguel-Angel; Giralt, Sergio; Sepkowitz, Kent; Papanicolaou, Genovefa A.; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2016)
After a cluster of fatal toxoplasmosis among stem cell transplant recipients at 2 hospitals, surveillance with polymerase chain reaction (PCR) (blood) was instituted. Rate of reactivation among seropositive recipients was 2.2 and 16%. Parasitemia was successfully managed with preemptive treatment. For seropositive recipients unable to take prophylaxis, toxoplasma PCR surveillance should be routinely performed.

Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America - Patterson, Thomas F.; Thompson, George R., III; Denning, David W.; Fishman, Jay A.; Hadley, Susan; Herbrecht, Raoul; Kontoyiannis, Dimitrios P.; Marr, Kieren A.; Morrison, Vicki A.; Nguyen, M. Hong; Segal, Brahm H.; Steinbach, William J.; et al. (Clinical Infectious Diseases, 2016)
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Crash Deaths in the US: Where We Stand - CDC (Centers for Disease Control and Prevention, 2016)
About 90 people die each day in the US from crashes—resulting in the highest death rate among 19 comparison countries. More can be done to improve road safety in the US.

Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis - Marty, Francisco M.; Ostrosky-Zeichner, Luis; Cornely, Oliver A.; Mullane, Kathleen M.; Perfect, John R.; Thompson, George R.; Alangaden, George J.; Brown, Janice M.; Fredricks, David N.; Heinz, Werner J.; Herbrecht, Raoul; Klimko, Nikolai; et al. (The Lancet Infectious Diseases, 2016)
Summary Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.

Similar rebleeding rate in 3-day and 7-day intravenous ceftriaxone prophylaxis for patients with acute variceal bleeding - Lee, Tzong-Hsi; Huang, Chung-Tsui; Lin, Chien-Chu; Chung, Chen-Shuan; Lin, Cheng-Kuan; Tsai, Kuang-Chau (Journal of the Formosan Medical Association = Taiwan Yi Zhi, 2016)
BACKGROUND/PURPOSE: Although prophylactic antibiotics have been recommended for cirrhotic patients with upper gastrointestinal bleeding, the duration of its use remains an inconclusive issue. We designed this study to investigate the duration of antibiotic prophylaxis for cirrhotic patients with acute esophageal variceal bleeding. METHODS: We enrolled those patients suffering from acute esophageal variceal bleeding and receiving band ligation. They were randomly allocated to two groups to receive prophylactic antibiotics; Group I: receiving intravenous ceftriaxone 500 mg every 12 hours for 3 days, and Group II: same regimen for 7 days. We used rebleeding rate within 14 days as the primary end point and also evaluated the survival rate within 28 days and the amount of transfusion during admission. RESULTS: There were 38 patients in Group I and 33 patients in Group II that completed the study course for analysis. Overall, there was no significant difference in the baseline characteristics between these two groups. There were three patients both in Group I and Group II who developed rebleeding within 14 days (8% vs. 9%, p > 0.99). There was also no difference between Group I and Group II in transfusion amount (2.71 ± 2.84 units vs. 3.18 ± 4.07, p = 0.839) and survival rate in 28 days (100 vs. 97%, p = 0.465). CONCLUSION: Our small scale study demonstrated that there was no difference in the rebleeding rate between 3-day and 7-day ceftriaxone prophylaxis for cirrhotic patients with acute esophageal variceal bleeding. There was also no difference in 28 day survival rate between these two groups.
Keywords: Administration, Intravenous; Adult; Aged; Antibiotic Prophylaxis; Bacterial Infections; Ceftriaxone; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Ligation; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Recurrence; Taiwan; antibiotic prophylaxis; ceftriaxone; esophageal variceal hemorrhage

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines - Styczynski, Jan; van der Velden, Walter; Fox, Christopher P.; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per (Haematologica, 2016)
Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5) - Mallet, Vincent; Bömmel, Florian van; Doerig, Christopher; Pischke, Sven; Hermine, Olivier; Locasciulli, Anna; Cordonnier, Catherine; Berg, Thomas; Moradpour, Darius; Wedemeyer, Heiner; Ljungman, Per (The Lancet Infectious Diseases, 2016)
Summary Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.

Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment - Dalle, Jean-Hugues; Giralt, Sergio A. (Biology of Blood and Marrow Transplantation, 2016)
Keywords: Hepatic veno-occlusive disease; Prophylaxis; Risk factors; Sinusoidal obstruction syndrome; Stem cell transplantation; Treatment

The 2015 International Society for Heart and Lung Transplantation Guidelines for the management of fungal infections in mechanical circulatory support and cardiothoracic organ transplant recipients: Executive summary - Husain, Shahid; Sole, Amparo; Alexander, Barbara D.; Aslam, Saima; Avery, Robin; Benden, Christian; Billaud, Eliane M.; Chambers, Daniel; Danziger-Isakov, Lara; Fedson, Savitri; Gould, Kate; Gregson, Aric; et al. (The Journal of Heart and Lung Transplantation, 2016)
Keywords: Adult; Assisted Circulation; Child; Heart-Lung Transplantation; Humans; Incidence; Mycoses; Postoperative Complications; Prevalence

Dematiaceous Molds - Wong, Eunice H.; Revankar, Sanjay G. (Infectious Disease Clinics of North America, 2016)
Keywords: Amphotericin B; Dematiaceous; Isavuconazole; Itraconazole; Phaeohyphomycosis; Posaconazole; Voriconazole

Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial - Maertens, Johan A.; Raad, Issam I.; Marr, Kieren A.; Patterson, Thomas F.; Kontoyiannis, Dimitrios P.; Cornely, Oliver A.; Bow, Eric J.; Rahav, Galia; Neofytos, Dionysios; Aoun, Mickael; Baddley, John W.; Giladi, Michael; et al. (The Lancet, 2016)
Summary Background Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease. Methods This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice–web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. Findings 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of −1·0% (95% CI −7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0·016), eye disorders (39 [15%] vs 69 [27%]; p=0·002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001). Interpretation Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.

Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America - Pappas, Peter G.; Kauffman, Carol A.; Andes, David R.; Clancy, Cornelius J.; Marr, Kieren A.; Ostrosky-Zeichner, Luis; Reboli, Annette C.; Schuster, Mindy G.; Vazquez, Jose A.; Walsh, Thomas J.; Zaoutis, Theoklis E.; Sobel, Jack D. (Clinical Infectious Diseases, 2016)
Abstract. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician

Contributory Role of Fluorine 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis and Clinical Management of Infections in Patients Supported With a Continuous-Flow Left Ventricular Assist Device - Dell’Aquila, Angelo Maria; Mastrobuoni, Stefano; Alles, Sebastian; Wenning, Christian; Henryk, Welp; Schneider, Stefan Rudolf Bertram; Deschka, Heinz; Sindermann, Jürgen R.; Scherer, Mirela (The Annals of Thoracic Surgery, 2016)
Background The current study sought to demonstrate the advantages offered by fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in patients supported with continuous-flow left ventricular assist devices (CF-LVADs) in detecting infection and the consequent effect on clinical decisions. Methods Between April 2009 and September 2013, 40 PET examinations were performed in 31 patients (78.1% men; mean age, 51.0 ± 14.9 years) supported with a CF-LVAD. In group A (19 examinations in 14 patients), PET/CT was performed to detect infectious focus in patients without external signs of driveline involvement but with at least two of the following infection signs: recurrent fever, positive blood culture, or elevated infectious indicators. In group B (21 examinations in 17 patients), PET/CT aimed to assess the internal extension of infection in patients with external signs of driveline infection. Results In 50% of the cases of the patients in group A, abnormal 18F-FDG uptake (9 patients) was related to VAD components. Matching the results with the final diagnosis, we reported 9 true-positive, 8 true-negative, no false-negative, and 2 false-positive findings. New information unrelated to VAD was found in 9 patients (50%): pneumonia in 3, colon diverticulitis in 3, sternal dehiscence in 1, paravertebral abscess in 1, and erysipelas in 1. In group B, superficial abnormal 18F-FDG uptake was found at the piercing site of the driveline in 2 patients, deeper extension of infection along the driveline in 10, initial involvement of the pump housing in 2, and full involvement of the device in 4. These findings contributed to changing the clinical management in 84.2% of group A patients and in 85.7% of group B patients: 16 patients were scheduled for urgent transplantation, 2 underwent surgical revision of the driveline, 7 required prolonged antibiotic therapy, and 3 underwent colonoscopy. Conclusions This single-center experience highlights the diagnostic value of PET/CT in detecting the localization and internal extension of infection to internal VAD components. Moreover, this information notably influences the therapeutic management.

ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients - Alanio, Alexandre; Hauser, Philippe M.; Lagrou, Katrien; Melchers, Willem J. G.; Helweg-Larsen, Jannik; Matos, Olga; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J. Peter; Cordonnier, Catherine; Maertens, Johan; et al. (Journal of Antimicrobial Chemotherapy, 2016)

Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon - Belga, Sara (World Journal of Gastroenterology, 2016)

How I vaccinate blood and marrow transplant recipients - Carpenter, Paul A.; Englund, Janet A. (Blood, 2016)

Mycobacterium bovis hip bursitis in a lung transplant recipient - Dan, J.m.; Crespo, M.; Silveira, F.p.; Kaplan, R.; Aslam, S. (Transplant Infectious Disease, 2016)
We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico–US border, clinical characteristics, resistance profile, and treatment.
Keywords: Mycobacterium bovis; extrapulmonary; hip bursitis; lung transplantation

False-positive hepatitis C virus serology after placement of a ventricular assistance device - Durand, C.M.; Marr, K.A.; Ostrander, D.; Subramanian, A.; Valsamakis, A.; Cox, A.; Neofytos, D. (Transplant Infectious Disease, 2016)

Mucormycoses - Farmakiotis, Dimitrios; Kontoyiannis, Dimitrios P. (Infectious Disease Clinics of North America, 2016)

Coccidioidomycosis Transmission Through Organ Transplantation: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee - Kusne, S.; Taranto, S.; Covington, S.; Kaul, D. R.; Blumberg, E. A.; Wolfe, C.; Green, M. (American Journal of Transplantation, 2016)
Donor-derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor-derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty-one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor-derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening.
Keywords: antibiotic: antifungal; clinical research/practice; complication: infectious; donors and donation: donor-derived infections; fungal; infection and infectious agents; infectious disease

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial - Origüen, J.; López‐Medrano, F.; Fernández‐Ruiz, M.; Polanco, N.; Gutiérrez, E.; González, E.; Mérida, E.; Ruiz‐Merlo, T.; Morales‐Cartagena, A.; Asín, M. A. Pérez-Jacoiste; García‐Reyne, A.; Juan, R. San; et al. (American Journal of Transplantation, 2016)
The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22–3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05–4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).
Keywords: antibiotic prophylaxis; bacterial; clinical decision-making; clinical research/practice; clinical trial; complication: infectious; infection and infectious agents; infectious disease; kidney transplantation/nephrology

Combination Antifungal Therapy for Invasive Aspergillosis Revisited - Panackal, Anil A. (Medical mycology: open access, 2016)
Invasive aspergillosis (IA) causes significant morbidity and mortality among immunocompromised hosts. Combination therapy with mold-active triazoles and echinocandins has been used with the hope of improving outcomes over monotherapy, especially in the setting of refractory disease. Herein, I update our prior systematic review and meta-analysis on combination therapy for salvage IA in the context of the recently published randomized clinical trial of combination therapy for primary IA. Clinicians should consider combination antifungals for IA in refractory disease despite immune reconstitution when there are concerns for resistance or pharmacokinetic variability.

OCULAR SYPHILIS IN A KIDNEY TRANSPLANT RECIPIENT - Romao, Elen A.; Bolella, Valdes R.; Nardin, Maria Estela P.; Habib-Simao, Maria Lucia; Furtado, João Marcelo; Moyses-Neto, Miguel (Revista Do Instituto De Medicina Tropical De Sao Paulo, 2016)
We present a case of ocular syphilis after a renal transplantation involving progressive vision loss without clinically identifiable ocular disease. Electroretinography showed signs of ischemia, especially in the internal retina. A serological test was positive for syphilis. Lumbar puncture revealed lymphocytic meningitis and a positive serologic test for syphilis in the cerebrospinal fluid. The patient was treated with penicillin, and had a quick vision improvement. In the case of transplant recipients, clinicians should always consider the diagnosis of ocular syphilis in cases with unexplained visual acuity decrement, as this condition may cause serious complications if not treated.
Keywords: Adult; Eye Infections, Bacterial; Humans; Kidney Transplantation; Male; Syphilis; Visual Acuity

Long-term outcomes of heart transplant recipients with hepatitis C positivity: the data from the U.S. transplant registry - Stepanova, Maria; Locklear, Trevor; Rafiq, Nila; Mishra, Alita; Venkatesan, Chapy; Younossi, Zobair M. (Clinical Transplantation, 2016)

Epidemiology and Risk Factors for Echinocandin Nonsusceptible Candida glabrata Bloodstream Infections: Data From a Large Multisite Population-Based Candidemia Surveillance Program, 2008–2014 - Vallabhaneni, Snigdha; Cleveland, Angela A.; Farley, Monica M.; Harrison, Lee H.; Schaffner, William; Beldavs, Zintar G.; Derado, Gordana; Pham, Cau D.; Lockhart, Shawn R.; Smith, Rachel M. (Open Forum Infectious Diseases, 2015)
Background. Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia., Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts population-based laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008–2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression., Results. Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6–1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2–5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0–3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0–6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure., Conclusion. The proportion of NS C glabrata isolates rose significantly during 2008–2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C glabrata without prior echinocandin exposure suggests possible transmission of resistant organisms.

50 Years of Emmonsia Disease in Humans: The Dramatic Emergence of a Cluster of Novel Fungal Pathogens - Schwartz, Ilan S.; Kenyon, Chris; Feng, Peiying; Govender, Nelesh P.; Dukik, Karolina; Sigler, Lynne; Jiang, Yanping; Stielow, J. Benjamin; Muñoz, José F.; Cuomo, Christina A.; Botha, Alfred; Stchigel, Alberto M.; et al. (PLOS Pathogens, 2015)
Keywords: Biopsy; Fungal diseases; Fungal pathogens; Fungal structure; Fungi; Pathogens; Respiratory infections; Yeast infections

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications - Baddour Larry M.; Wilson Walter R.; Bayer Arnold S.; Fowler Vance G.; Tleyjeh Imad M.; Rybak Michael J.; Barsic Bruno; Lockhart Peter B.; Gewitz Michael H.; Levison Matthew E.; Bolger Ann F.; Steckelberg James M.; et al. (Circulation, 2015)
Background—Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today’s myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.Methods and Results—This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.Conclusions—Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adultsa - Berbari, Elie F.; Kanj, Souha S.; Kowalski, Todd J.; Darouiche, Rabih O.; Widmer, Andreas F.; Schmitt, Steven K.; Hendershot, Edward F.; Holtom, Paul D.; Huddleston, Paul M., III; Petermann, Gregory W.; Osmon, Douglas R. (Clinical Infectious Diseases, 2015)
These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Bill Text - AB-258 Organ transplants: medical marijuana: qualified patients. (2015)
This bill would prohibit a hospital, physician and surgeon, procurement organization, or other person from determining the ultimate recipient of an anatomical gift based solely upon a potential recipient’s status as a qualified patient, as specified, or based solely upon a positive test for the use of medical marijuana by a potential recipient who is a qualified patient, except to the extent that the qualified patient’s use of medical marijuana has been found by a physician and surgeon, following a case-by-case evaluation of the potential recipient, to be medically significant to the provision of the anatomical gift. The bill would provide that these provisions shall not be deemed to require referrals or recommendations for, or the performance of, medically iappropriate organ transplants.

Treatment of Ampicillin-Resistant Enterococcus faecium Urinary Tract Infections - Richey, Erica M.; Waters, Patrick W.; Jovic, Milica; Rakhman, Claudia (Federal Practitioner, 2015)
There was no statistically significant difference between amoxicillin and nitrofurantoin for the treatment of ampicillin-resistant Enterococcus faecium urinary tract infections.

Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus - van der Linden, J.W.M.; Arendrup, M.C.; Warris, A.; Lagrou, K.; Pelloux, H.; Hauser, P.M.; Chryssanthou, E.; Mellado, E.; Kidd, S.E.; Tortorano, A.M.; Dannaoui, E.; Gaustad, P.; et al. (Emerging Infectious Diseases, 2015)
To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

Latent Mycobacterium tuberculosis Infection - Getahun, Haileyesus; Matteelli, Alberto; Chaisson, Richard E.; Raviglione, Mario (New England Journal of Medicine, 2015)

Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex - Hagen, Ferry; Khayhan, Kantarawee; Theelen, Bart; Kolecka, Anna; Polacheck, Itzhack; Sionov, Edward; Falk, Rama; Parnmen, Sittiporn; Lumbsch, H. Thorsten; Boekhout, Teun (Fungal Genetics and Biology, 2015)
Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.
Keywords: Cryptic species; Pathogen; Taxonomy; Yeast

British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases - Schelenz, Silke; Barnes, Rosemary A.; Barton, Richard C.; Cleverley, Joanne R.; Lucas, Sebastian B.; Kibbler, Christopher C.; Denning, David W. (The Lancet Infectious Diseases, 2015)
Summary Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. We therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically significant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, we provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, we consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients.

Engraftment syndrome: double-edged sword of hematopoietic cell transplants - Spitzer, T. R. (Bone Marrow Transplantation, 2015)
Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is increasingly diagnosed. Common features include fever, pulmonary vascular leak, rash and organ dysfunction. Different diagnostic criteria likely account for the wide (7–90%) range of reported incidences. ES typically occurs within 4 days of granulocyte recovery although a recently described seemingly similar syndrome occurs >1 week before granulocyte recovery after umbilical cord blood cell transplants. Although the clinical manifestations of ES may be identical to those of acute GVHD, ES also has been well described in patients without acute GVHD. The data are conflicting as to whether ES is associated with a higher nonrelapse mortality and worse survival after HCT. The pathophysiology of ES is unclear, but endothelial injury and activated granulocytes in the setting of proinflammatory cytokines may be important. ES typically is self-limited, but, like acute GVHD, responds to corticosteroids. Because ES and acute GVHD may have overlapping features and response to therapy, these disease processes may often not be distinct events. Moreover, features of ES may overlap with those of drug- and radiation-induced toxicities and infection. Further research to better characterize the clinical spectrum and etiology of ES and to determine its relationship to GVHD is needed.

HIV-Positive–to–HIV-Positive Kidney Transplantation — Results at 3 to 5 Years - Muller, Elmi; Barday, Zunaid; Mendelson, Marc; Kahn, Delawir (New England Journal of Medicine, 2015)

Combination antifungal therapy for invasive aspergillosis: a randomized trial - Marr, Kieren A.; Schlamm, Haran T.; Herbrecht, Raoul; Rottinghaus, Scott T.; Bow, Eric J.; Cornely, Oliver A.; Heinz, Werner J.; Jagannatha, Shyla; Koh, Liang Piu; Kontoyiannis, Dimitrios P.; Lee, Dong-Gun; Nucci, Marcio; et al. (Annals of Internal Medicine, 2015)
BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. OBJECTIVE: To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479). SETTING: 93 international sites. PATIENTS: 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. MEASUREMENTS: The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. RESULTS: Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P  = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. LIMITATIONS: Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. CONCLUSION: Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. PRIMARY FUNDING SOURCE: Pfizer.
Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Aspergillosis; Double-Blind Method; Drug Therapy, Combination; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Karnofsky Performance Status; Male; Mannans; Middle Aged; Platelet Count; Treatment Outcome; Voriconazole; Young Adult

Travel risk assessment, advice and vaccinations in immunocompromised travellers (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients): A review - Aung, A. K.; Trubiano, J. A.; Spelman, D. W. (Travel Medicine and Infectious Disease, 2015)
International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity.
Keywords: Haematopoietic stem cell transplant; Human immunodeficiency virus; Infections; Risk management; Solid organ transplant

Predictors of Immune Reconstitution Syndrome in Organ Transplant Recipients With Cryptococcosis: Implications for the Management of Immunosuppression - Sun, Hsin-Yun; Alexander, Barbara D.; Huprikar, Shirish; Forrest, Graeme N.; Bruno, Didier; Lyon, G. Marshall; Wray, Dannah; Johnson, Leonard B.; Sifri, Costi D.; Razonable, Raymund R.; Morris, Michele I.; Stoser, Valentina; et al. (Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2015)
Authors determined variables that pose a risk for immune reconstitution syndrome (IRS) and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis., Background. Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined., Methods. SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria., Results. Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ2 for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07)., Conclusions. We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.

Donor-Derived Strongyloides stercoralis Infection in Solid Organ Transplant Recipients in the United States, 2009-2013: Donor-Derived Strongyloides stercoralis Infection - Abanyie, F. A.; Gray, E. B.; Delli Carpini, K. W.; Yanofsky, A.; McAuliffe, I.; Rana, M.; Chin-Hong, P. V.; Barone, C. N.; Davis, J. L.; Montgomery, S. P.; Huprikar, S. (American Journal of Transplantation, 2015)

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections - Agut, Henri; Bonnafous, Pascale; Gautheret-Dejean, Agnès (Clinical Microbiology Reviews, 2015)

Efficacy of once-weekly dapsone dosing for Pneumocystis jirovecii pneumonia prophylaxis post transplantation - Evans, R.A.; Clifford, T.M.; Tang, S.; Au, T.; Fugit, A.M. (Transplant Infectious Disease, 2015)

Solid Organ Transplantation From Hepatitis B Virus-Positive Donors: Consensus Guidelines for Recipient Management: Transplantation From Hepatitis B Virus-Positive Donors - Huprikar, S.; Danziger-Isakov, L.; Ahn, J.; Naugler, S.; Blumberg, E.; Avery, R. K.; Koval, C.; Lease, E. D.; Pillai, A.; Doucette, K. E.; Levitsky, J.; Morris, M. I.; et al. (American Journal of Transplantation, 2015)

Role of Gallium SPECT-CT in the Diagnosis of Left Ventricular Assist Device Infections: - Levy, Dana T.; Minamoto, Grace Y.; Da Silva, Raphaella; Puius, Yoram A.; Peck, Naomi; Goldstein, Daniel; D’Alessandro, David; Muggia, Victoria A. (ASAIO Journal, 2015)

Outcomes of Heart Transplant After Left Ventricular Assist Device Specific and Related Infection - Tong, Michael Z.; Smedira, Nicholas G.; Soltesz, Edward G.; Starling, Randall C.; Koval, Christine E.; Porepa, Liane; Moazami, Nader (The Annals of Thoracic Surgery, 2015)

Observations on the use of cidofovir for BK virus infection in renal transplantation - Kuten, S. A.; Patel, S. J.; Knight, R. J.; Gaber, L. W.; DeVos, J. M.; Gaber, A. O. (Transplant Infectious Disease, 2014)
Background In renal transplantation, BK virus infection can result in significant graft nephropathy and loss. While reduction in immunosuppression (IS) is considered standard therapy, adjunct agents may be warranted. Data are suggestive of a possible role of cidofovir for the management of BK. This study aims to describe the course of BK viremia (BKV) in a large cohort of renal transplant patients receiving adjunct cidofovir. Methods We evaluated kidney and kidney-pancreas recipients who received cidofovir combined with reduced IS for management of high-level BKV or BK virus nephropathy (BKVN). We examined the rate and timing of BKV clearance, and performed a multivariate analysis to identify risk factors associated with long-term (>6 months) viremia. Results In total, 75 patients received a median of 13 doses of cidofovir in conjunction with reduced IS; 32 patients (43%) had short-term BKV (≤6 months), and 43 (57%) had long-term BKV. Overall, 53 of 75 patients (71%) eventually cleared BKV at a median of 4.2 months (interquartile range 2.1–9.3 months). Independent factors associated with long-term BKV included older age (odds ratio [OR] 1.1, P = 0.02), delayed graft function (OR 31.4, P = 0.01), and higher peak BKV (OR 12.8, P = 0.02), while BKV reduction by at least 1 log10copies/mL at 1 month of treatment was associated with clearance within 6 months (OR 49.3, P < 0.01). Patients with earlier clearance maintained stable graft function and no graft losses, while long-term BKV was associated with a 15% decline in estimated glomerular filtration rate. Conclusions Adjunct cidofovir resulted in preservation of renal function when viral clearance occurred within 6 months of initiation. This retrospective review defines factors predicting response to cidofovir in conjunction with reduced IS for BKVN or high-level BKV. Still, considering cost, frequency of administration, and treatment duration, a randomized trial is necessary to define the exact utility of cidofovir in the setting of BK virus infection.
Keywords: BK virus; antiviral; cidofovir; renal transplantation

Bacterial foodborne infections after hematopoietic cell transplantation - Boyle, Nicole M.; Podczervinski, Sara; Jordan, Kim; Stednick, Zach; Butler-Wu, Susan; McMillen, Kerry; Pergam, Steven A. (Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, 2014)
Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella, Vibrio, or E. coli O157:H7 were detected. Most patients were diagnosed via stool (8 of 12 [67%]), fewer through blood (2 of 12 [17%]), 1 via both stool and blood simultaneously, and 1 through urine. Mortality due to bacterial foodborne infection was not observed during follow-up. Our large single-center study indicates that common bacterial foodborne infections were a rare complication after HCT, and the few cases that did occur resolved without complications. These data provide important baseline incidence for future studies evaluating dietary interventions for HCT patients.
Keywords: Adult; Aged; Bacteria; Bacterial Infections; Campylobacter; Data Collection; Diet; Female; Foodborne; Foodborne Diseases; Hematopoietic; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Retrospective Studies; Transplantation; Transplantation Conditioning

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America - Stevens, Dennis L.; Bisno, Alan L.; Chambers, Henry F.; Dellinger, E. Patchen; Goldstein, Ellie J. C.; Gorbach, Sherwood L.; Hirschmann, Jan V.; Kaplan, Sheldon L.; Montoya, Jose G.; Wade, James C. (Clinical Infectious Diseases, 2014)

Vibrio parahaemolyticus: A Rare Cause of Chronic Diarrhea in a Heart Transplant Patient - Shuja, Asim; Dickstein, Aaron; Lee, Hannah M. (ACG Case Reports Journal, 2014)
Vibrio parahaemolyticus usually causes a self-limiting acute diarrheal illness, and is rarely tested for in cases of chronic diarrhea. We present a rare case of chronic diarrhea caused by V. parahaemolyticus in a heart transplant patient requiring antibiotic treatment.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients - Lion, Thomas (Clinical Microbiology Reviews, 2014)
Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

Fecal Microbiota Transplant for Treatment of Clostridium difficile Infection in Immunocompromised Patients - Kelly, Colleen R.; Ihunnah, Chioma; Fischer, Monika; Khoruts, Alexander; Surawicz, Christina; Afzali, Anita; Aroniadis, Olga; Barto, Amy; Borody, Thomas; Giovanelli, Andrea; Gordon, Shelley; Gluck, Michael; et al. (The American journal of gastroenterology, 2014)
OBJECTIVES Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients. METHODS A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT. RESULTS Cases included adult (75) and pediatric () patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3–46 months). Reasons for IC included: HIV/AIDS (), solid organ transplant (), oncologic condition (), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC > 100 days after FMT. CONCLUSIONS This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Evaluation of the Pediatric Patient for Liver Transplantation: 2014 Practice Guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition - Squires, Robert H.; Ng, Vicky; Romero, Rene; Ekong, Udeme; Hardikar, Winita; Emre, Sukru; Mazariegos, George V. (Hepatology, 2014)
An abstract is unavailable.

How I treat sinusoidal obstruction syndrome - Chao, N. (Blood, 2014)

Single Donor-Derived Strongyloidiasis in Three Solid Organ Transplant Recipients: Case Series and Review of the Literature - Le, M.; Ravin, K.; Hasan, A.; Clauss, H.; Muchant, D. G.; Pasko, J. K.; Cipollina, G.; Abanyie, F.; Montgomery, S. P.; Loy, M.; Ahmed, M.; Mathur, M.; et al. (American Journal of Transplantation, 2014)
Donor-derived Strongyloides stercoralis infections in transplant recipients are a rare but recognized complication. In this case series, we report donor-derived allograft transmission of Strongyloides in three solid organ transplant recipients. Following detection of infection in heart and kidney–pancreas recipients at two different transplant centers, a third recipient from the same donor was identified and diagnosed. S. stercoralis larvae were detected in duodenal aspirates, bronchial washings, cerebrospinal fluid, urine and stool specimens. Treatment with ivermectin and albendazole was successful in two of the three patients identified. The Centers for Disease Control and Prevention was contacted and performed an epidemiologic investigation. Donor serology was strongly positive for S. stercoralis antibodies on retrospective testing while all pretransplant recipient serum was negative. There should be a high index of suspicion for parasitic infection in transplant recipients and donors from endemic regions of the world. This case series underscores the need for expanded transplant screening protocols for Strongyloides. Positive serologic or stool tests should prompt early treatment or prophylaxis in donors and recipients as well as timely notification of organ procurement organizations and transplant centers.
Keywords: Donor screening; Strongyloides; donor-to-host transmission; heart transplantation; renal and pancreas transplantation; renal transplant; strongyloidiasis; survivors; transplant infectious diseases

ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of rare invasive yeast infections - Arendrup, M. C.; Boekhout, T.; Akova, M.; Meis, J. F.; Cornely, O. A.; Lortholary, O. (Clinical Microbiology and Infection, 2014)
Abstract The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive treatment was reviewed. In addition, remarks about antifungal susceptibility testing were made.

Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation - Martin, Paul; DiMartini, Andrea; Feng, Sandy; Brown, Robert Jr; Fallon, Michael (Hepatology, 2014)
An abstract is unavailable.

Fecal Microbiota Transplantation for Refractory Clostridium difficile Colitis in Solid Organ Transplant Recipients - Friedman‐Moraco, R. J.; Mehta, A. K.; Lyon, G. M.; Kraft, C. S. (American Journal of Transplantation, 2014)
Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile. It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile. Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression.
Keywords: Clostridium difficile; fecal microbiota transplantation; fecal transplant; lung transplant; renal transplant; solid organ transplant

2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host - Rubin, Lorry G.; Levin, Myron J.; Ljungman, Per; Davies, E. Graham; Avery, Robin; Tomblyn, Marcie; Bousvaros, Athos; Dhanireddy, Shireesha; Sung, Lillian; Keyserling, Harry; Kang, Insoo (Clinical Infectious Diseases, 2014)

Management of infections related to totally implantable venous-access ports: challenges and perspectives - Lebeaux, David; Fernández-Hidalgo, Nuria; Chauhan, Ashwini; Lee, Samuel; Ghigo, Jean-Marc; Almirante, Benito; Beloin, Christophe (The Lancet Infectious Diseases, 2014)
Use of totally implantable venous-access ports (TIVAPs) is standard practice for patients with diseases such as solid-tumour cancers, haematological malignancies, and chronic digestive diseases. Use of TIVAPs allows long-term administration of venotoxic compounds, improves patients' quality of life, and reduces the risk of infection. Microbial contamination, formation of pathogenic biofilms, and infection, however, are associated with morbidity, mortality, and increased health-care costs. Local and systemic complications or infections related to specific pathogens might lead to device removal. Alternatively, conservative treatment with combined systemic antibiotics and antibiotic lock therapy might be useful. We discuss in-vitro and in-vivo basic and clinical research findings on the epidemiology, diagnosis, and prevention of TIVAP-related infections, the current challenges to management, promising strategies, and some treatments in development that are likely to improve outcomes of TIVAP-related infections, with a particular focus on antibiotic lock therapy.

ESCMID and ECMM joint clinical guidelines for the diagnosis and management of systemic phaeohyphomycosis: diseases caused by black fungi - Chowdhary, A.; Meis, J.F.; Guarro, J.; de Hoog, G.S.; Kathuria, S.; Arendrup, M.C.; Arikan-Akdagli, S.; Akova, M.; Boekhout, T.; Caira, M.; Guinea, J.; Chakrabarti, A.; et al. (Clinical Microbiology and Infection, 2014)

ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013 - Cornely, O.A.; Arikan-Akdagli, S.; Dannaoui, E.; Groll, A.H.; Lagrou, K.; Chakrabarti, A.; Lanternier, F.; Pagano, L.; Skiada, A.; Akova, M.; Arendrup, M.C.; Boekhout, T.; et al. (Clinical Microbiology and Infection, 2014)

Capacity building in pediatric transplant infectious diseases: An international perspective - Danziger-Isakov, Lara; Evans, Helen M.; Green, Michael; McCulloch, Mignon; Michaels, Marian G.; Posfay-Barbe, Klara M.; Verma, Anita; Allen, Upton (Pediatric Transplantation, 2014)
Transplant infectious diseases is a rapidly emerging subspecialty within pediatric infectious diseases reflecting the increasing volumes and complexity of this patient population. Incorporating transplant infectious diseases into the transplant process would provide an opportunity to improve clinical outcome and advocacy as well as expand research. The relationship between transplant physicians and infectious diseases (ID) specialists is one of partnership, collaboration, and mutual continuing professional education. The ID CARE Committee of the International Pediatric Transplant Association (IPTA) views the development and integration of transplant infectious diseases into pediatric transplant care as an international priority.
Keywords: Pediatric; education; infectious diseases; transplant

Hepatitis E Virus Infection - Kamar, Nassim; Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques (Clinical Microbiology Reviews, 2014)
SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries.

Considerations for Screening Live Kidney Donors for Endemic Infections: A Viewpoint on the UNOS Policy: Live Kidney Donor Screening for Endemic Infections - Levi, M. E.; Kumar, D.; Green, M.; Ison, M. G.; Kaul, D.; Michaels, M. G.; Morris, M. I.; Schwartz, B. S.; Echenique, I. A.; Blumberg, E. A.; on behalf of the AST ID Community of Practice (American Journal of Transplantation, 2014)

Graft-Versus-Host Disease After Simultaneous Pancreas-Kidney Transplantation: A Case Report and Review of the Literature: GVHD After Pancreas-Kidney Transplantation - Rossi, A. P.; Bone, B. A.; Edwards, A. R.; Parker, M. K.; Delos Santos, R. B.; Hagopian, J.; Lockwood, C.; Musiek, A.; Klein, C. L.; Brennan, D. C. (American Journal of Transplantation, 2014)

ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others - Tortorano, A.M.; Richardson, M.; Roilides, E.; van Diepeningen, A.; Caira, M.; Munoz, P.; Johnson, E.; Meletiadis, J.; Pana, Z.-D.; Lackner, M.; Verweij, P.; Freiberger, T.; et al. (Clinical Microbiology and Infection, 2014)

Clinical Manifestations and Management of Left Ventricular Assist Device-Associated Infections - Nienaber, J. J. C.; Kusne, S.; Riaz, T.; Walker, R. C.; Baddour, L. M.; Wright, A. J.; Park, S. J.; Vikram, H. R.; Keating, M. R.; Arabia, F. A.; Lahr, B. D.; Sohail, M. R.; et al. (Clinical Infectious Diseases, 2013)

Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients - Krishna, S. G.; Zhao, W.; Apewokin, S. K.; Krishna, K.; Chepyala, P.; Anaissie, E. J. (Transplant Infectious Disease, 2013)
Background Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high-dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea. Methods A total of 303 consecutive MM patients (2004–2007) were enrolled in a protocol consisting of induction chemotherapy, tandem melphalan (MEL)-ASCT, and consolidation. Patients with grade 2–4 diarrhea were simultaneously tested for CDI, and initiated on antiperistaltic agents (loperamide) and preemptive anti-CDI therapy. Risk factors, including prior CDI and MM immunoglobulin (Ig) isotype, were evaluated. Multinomial logistic regression was used to compute the relative risk ratio (RRR) and 95% confidence intervals (CIs). Results There were 43 cases of CDI (14.2%) during 1529 chemotherapy courses (536 ASCT). IgA MM protected against CDI (RRR 0.35; 95% CI 0.13–0.93, P = 0.04) whereas CDI during first induction markedly increased the risk of recurrence during second induction (RRR = 10.94; 95% CI 1.90, 62.92, P = 0.01) and following MEL-ASCT (RRR = 6.63; 95% CI 1.51, 29.12, P = 0.01). No CDI-related surgical intervention or death ensued despite use of antiperistaltic agents. Conclusions CDI was not uncommon in cancer patients receiving chemotherapy. IgA myeloma appears to be protective. Concurrent antiperistaltic (loperamide) and preemptive CDI therapies were associated with excellent outcomes. Prior CDI history increased the risk for recurrence during successive chemotherapy courses.
Keywords: Clostridium difficile; anti-motility drugs; antiperistaltic drugs; chemotherapy; loperamide; lower alimentary tract mucositis; multiple myeloma; stem cell transplantation

Diagnosis and treatment of adenovirus infection in immunocompromised patients - Matthes-Martin, Susanne; Boztug, Heidrun; Lion, Thomas (Expert Review of Anti-Infective Therapy; London, 2013)
In immunocompromised patients, human adenovirus (HAdV) infections can cause life-threatening multiorgan disease. This review summarizes the incidence and risk factors of invasive human adenovirus infections in immunocompromised patients as well as the recently developed standards for diagnostic methods and strategies according to the predominant risk factors in adults and children. Recommendations for preemptive and therapeutic treatment strategies and the outcome in different risk groups are presented. Novel therapeutic approaches including CMX001, a new orally bioavailable lipid conjugate of cidofovir and the transfer of adenovirus-specific donor T cells in the context of allogeneic stem cell transplantation are discussed.
Keywords: CMX001; Medical Sciences--Allergology And Immunology; Medical Sciences--Communicable Diseases; Medical Sciences--Physical Medicine And Rehabilitation; adenovirus; chemotherapy; cidofovir; immunocompromised patients; organ transplantation; stem cell transplantation; viral infection; virus-specific T cells

Donor-derived Trypanosoma cruzi infection in solid organ recipients in the United States, 2001-2011 - Huprikar, S.; Bosserman, E.; Patel, G.; Moore, A.; Pinney, S.; Anyanwu, A.; Neofytos, D.; Ketterer, D.; Striker, R.; Silveira, F.; Qvarnstrom, Y.; Steurer, F.; et al. (American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2013)
Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.
Keywords: Adult; Aged; Chagas; Chagas Disease; Female; Humans; Male; Middle Aged; Nitroimidazoles; Organ Transplantation; Polymerase Chain Reaction; Tissue Donors; Trypanosoma cruzi; United States; donor; transmission; transplantation

Relapsing Brucellosis After Liver Transplantation in a Child: What Is the Appropriate Regimen and Duration of Therapy? - Islek, Ali; Sayar, Ersin; Yilmaz, Aygen; Günseren, Filiz; Artan, Reha (Transplantation, 2013)
An abstract is unavailable.
Keywords: Anti-Infective Agents; Antitubercular Agents; Brucellosis; Child; Female; Humans; Immunocompromised Host; Liver Transplantation; Opportunistic Infections; Postoperative Complications; Recurrence; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP) - McLean, Huong Q.; Fiebelkorn, Amy Parker; Temte, Jonathan L.; Wallace, Gregory S.; Centers for Disease Control and Prevention (MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports, 2013)
This report is a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps. The report presents the recent revisions adopted by the Advisory Committee on Immunization Practices (ACIP) on October 24, 2012, and also summarizes all existing ACIP recommendations that have been published previously during 1998-2011 (CDC. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1998;47[No. RR-8]; CDC. Revised ACIP recommendation for avoiding pregnancy after receiving a rubellacontaining vaccine. MMWR 2001;50:1117; CDC. Updated recommendations of the Advisory Committee on Immunization Practices [ACIP] for the control and elimination of mumps. MMWR 2006;55:629-30; and, CDC. Immunization of healthcare personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60[No. RR-7]). Currently, ACIP recommends 2 doses of MMR vaccine routinely for children with the first dose administered at age 12 through 15 months and the second dose administered at age 4 through 6 years before school entry. Two doses are recommended for adults at high risk for exposure and transmission (e.g., students attending colleges or other post-high school educational institutions, healthcare personnel, and international travelers) and 1 dose for other adults aged ≥18 years. For prevention of rubella, 1 dose of MMR vaccine is recommended for persons aged ≥12 months. At the October 24, 2012 meeting, ACIP adopted the following revisions, which are published here for the first time. These included: • For acceptable evidence of immunity, removing documentation of physician diagnosed disease as an acceptable criterion for evidence of immunity for measles and mumps, and including laboratory confirmation of disease as a criterion for acceptable evidence of immunity for measles, rubella, and mumps. • For persons with human immunodeficiency virus (HIV) infection, expanding recommendations for vaccination to all persons aged ≥12 months with HIV infection who do not have evidence of current severe immunosuppression; recommending revaccination of persons with perinatal HIV infection who were vaccinated before establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established; and changing the recommended timing of the 2 doses of MMR vaccine for HIV-infected persons to age 12 through 15 months and 4 through 6 years. • For measles postexposure prophylaxis, expanding recommendations for use of immune globulin administered intramuscularly (IGIM) to include infants aged birth to 6 months exposed to measles; increasing the recommended dose of IGIM for immunocompetent persons; and recommending use of immune globulin administered intravenously (IGIV) for severely immunocompromised persons and pregnant women without evidence of measles immunity who are exposed to measles. As a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps, the information in this report is intended for use by clinicians as baseline guidance for scheduling of vaccinations for these conditions and considerations regarding vaccination of special populations. ACIP recommendations are reviewed periodically and are revised as indicated when new information becomes available.
Keywords: Adolescent; Adult; Advisory Committees; Child; Child, Preschool; Female; Humans; Immunization Schedule; Infant; Male; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Practice Guidelines as Topic; Pregnancy; Rubella; Rubella Syndrome, Congenital; United States