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Background Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis. Methods We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023. Results We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%. Conclusions In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile infection ( CDI) is a significant complication of allogeneic hematopoietic stem cell transplantation (allo- HSCT). Our primary objective was to determine risk factors for the development of CDI during the first year following allo- HSCT. Methods A matched case-control study nested in a cohort of allo- HSCT at a single hospital in Montréal, Québec, Canada, was conducted from 2002 through 2011. Results Sixty-five of 760 patients who underwent allo- HSCT between 2002 and 2011 developed CDI, representing an incidence of 8.6%. We selected 123 controls matched for year of transplant for risk factor analyses. In the multivariable analysis, receipt of trimethoprim-sulfamethoxazole ( TMP- SMX) prior to transplantation (adjusted odds ratio [ aOR] 0.07, 95% confidence interval [ CI] 0.02-0.27), mucositis ( aOR 5.90, 95% CI 2.08-16.72), and reactivation of cytomegalovirus ( CMV) ( aOR 6.17, 95% CI 2.17-17.57) and of other Herpesviridae viruses ( aOR 3.04, 95% CI 1.13-8.16) were the variables that remained statistically associated with CDI. High-risk antibiotic use in the late post-transplant period ( aOR 7.63, 95% CI 2.14-27.22) was associated with development of late CDI. Conclusion This study revealed reactivation of CMV and other Herpesviridae viruses as novel risk factors for CDI. Administration of TMP- SMX prior to transplantation was independently associated with a decreased risk of CDI. Early and late CDI after HSCT may have distinct risk factors. [ABSTRACT FROM AUTHOR]