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Fungal infections in recipients of solid organ and hematopoietic stem cell transplant recipients are significant causes of morbidity and mortality. Though relatively uncommon compared to other infectious complications, the difficulty in making a timely diagnosis and effectively treating patients presents a daunting challenge. Among the fungi responsible for these infections, there are many that are rarely encountered clinically yet are associated with high mortality in transplant patients....
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Pneumocystis pneumonia (PJP) is caused by Pneumocystis jiroveci and is an important infection of chronically immunocompromised patients, especially those receiving higher doses of corticosteroids and those with abnormalities in cell-mediated immunity. Until recently, the vast majority of cases were in HIV patients. This has changed with an increasing proportion occurring in non-HIV patients, including in solid organ and hematopoietic stem cell transplant recipients. The risk factors,...
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The survival benefit of combination antifungal therapy for Invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined.This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between Jan 1, 2007-Dec 31, 2017 from ten transplant centers across North America.Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 EORTC/MSG consensus definitions were included....
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Hematopoietic transplantation is the preferred treatment for many patients with hematologic malignancies. Some patients may develop invasive fungal diseases (IFDs) during initial chemotherapy, which need to be considered when assessing patients for transplantation and treatment posttransplantation. Given the associated high risk of relapse and mortality in the post–hematopoietic stem cell transplantation (HSCT) period, IFDs, especially invasive mold diseases, were historically considered a...
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The increasing emergence and spread of drug resistant Candida albicans represent a serious challenge for effective treatment and call for the development of new therapeutic options. To address this need, we synthesized a series of polypyridyl iridium(III) complexes and studied their antimicrobial activities. Herein, one lead iridium(III) complex Ir-3 [(ptpy)2Ir(dppz)]PF6, with ptpy = 2-(p-tolyl)pyridine and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, exhibited potent and broad-spectrum...
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Background. Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). It is unclear how a targeted prophylaxis/ preemptive antifungal therapy strategy impacts the incidence of IPA beyond the first-year posttransplant. Methods. This is a retrospective cohort of LTRs from January 2010 to December 2014. We included all LTRs who survived beyond the first year and followed them until death or 4 years...
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Abstract. Mucormycosis is one of the most complicated to diagnose and treat invasive fungal diseases. Diagnostic techniques have not significantly advanced in y
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BACKGROUND: Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in-vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series but may have a lower barrier to resistance. No comparative studies have been published. METHODS: We constructed a single-center retrospective cohort of adult patients diagnosed...
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Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC).Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS...
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<h2>Abstract</h2><h3>Background</h3><p><i>Pneumocystis jirovecii</i> pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.</p><h3>Method</h3><p>We carried out a systematic review and meta-analysis using articles in the English language published...
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In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal...
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Data on invasive mold infections (IMIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. We describe 2 patients with post–CAR-T-cell IMI (Fusarium, Mucorales) and review the published literature. We propose strategies to prevent IMIs in patients, based on the IMI rate and presence of neutropenia or steroid use.
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Background Pneumocystis jirovecii pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15–20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety...
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Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and...
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Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures...
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<h2>Summary</h2><p>Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis...
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Objectives: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY078), a novel orally bioavailable b-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 lMÁh) in .80% of the intended population. Methods: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three...
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BACKGROUND: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. METHODS: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a...
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