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Background. Cancer is a known risk factor for developing active tuberculosis. We determined the incidence and relative risk of active tuberculosis in cancer patients compared to the general population. Methods. Medline, Medline InProcess, EMBASE, PubMed, the Cochrane Database of Systematic Reviews, Cancerlit, and Web of Science were searched up to December 1, 2015. Studies of pathologically confirmed cancer cases were included if active tuberculosis was identified concurrently or after diagnosis. Cumulative incidence rate/100 000 population (CIR) of new cases of tuberculosis occurring in cancer patients and comparative incidence rate ratios (IRRs) to the general population from the same country of origin were estimated. A random effect meta-analysis was conducted on the CIR and IRR. Results. A total of 23 studies reporting 593 tuberculosis cases occurring in 324 041 cancer patients between 1950 and 2011 were identified. In a meta-analysis of 6 studies conducted in the United States in 317 243 cancer patients (98% of all patients), the CIR of tuberculosis decreased by 3-fold and 6.5-fold in hematologic and solid cancers, respectively, before and after 1980. After 1980 the CIR of tuberculosis was highest in hematologic (219/100 000 population; IRR = 26), head and neck (143; 16), lung cancers (83; 9) and was lowest in breast and other solid cancers (38; 4). Conclusions. Individuals living in the United States with hematologic, head and neck, and lung cancers had a 9-fold higher rate of developing active tuberculosis compared to those without cancer and would benefit from targeted latent tuberculosis screening and therapy. [ABSTRACT FROM AUTHOR]

Background. Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. Methods. This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. Results. We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. Conclusions. This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management. [ABSTRACT FROM AUTHOR]

Background. Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI). Methods. Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression. Results. A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age =80 years, heart rate >90/minute, respiratory rate >20/ minute, white cell count <4 × 109/L or =20 × 109/L, albumin <25 g/L, blood urea nitrogen >7 mmol/L, and C-reactive protein =150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis. Conclusions. CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile infection (CDI) can lead to complications, recurrence, and death. Numerous studies have assessed risk factors for these unfavourable outcomes, but systematic reviews or meta-analyses published so far were limited in scope or in quality. Methods: A systematic review was completed according to PRISMA guidelines. An electronic search in five databases was performed. Studies published until October 2013 were included if risk factors for at least one CDI outcome were assessed with multivariate analyses. Results: 68 studies were included: 24 assessed risk factors for recurrence, 18 for complicated CDI, 8 for treatment failure, and 30 for mortality. Most studies accounted for mortality in the definition of complicated CDI. Important variables were inconsistently reported, such as previous episodes and use of antibiotics. Substantial heterogeneity and methodological limitations were noted, mainly in the sample size, the definition of the outcomes and periods of follow-up, precluding a meta-analysis. Older age, use of antibiotics after diagnosis, use of proton pump inhibitors, and strain type were the most frequent risk factors for recurrence. Older age, leucocytosis, renal failure and co-morbidities were frequent risk factors for complicated CDI. When considered alone, mortality was associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal failure, and infection with ribotype 027. Conclusion: Laboratory parameters currently used in European and American guidelines to define patients at risk of a complicated CDI are adequate. Strategies for the management of CDI should be tailored according to the age of the patient, biological markers of severity, and underlying co-morbidities. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Potential conflicts of interest . S. F. D. has received honoraria for consultancy and research funding from AVIR Pharma Inc and Merck & Co. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Outcomes associated with physician responses to recommendations from an antimicrobial stewardship program (ASP) at an individual patient level have not yet been assessed. We aimed to compare clinical characteristics and mortality risk among patients for whom recommendations from an ASP were accepted or refused., Methods: A prospective cohort study was performed with hospitalized adults who received intravenous or oral antimicrobials at a 677-bed academic centre in Canada in 2014-2017. We included patients with an alert produced by a clinical decision support system (CDSS) for whom a recommendation was made by the pharmacist to the attending physician. The outcome was 90-day in-hospital all-cause mortality., Results: We identified 3,197 recommendations throughout the study period, of which 2,885 (90.2%) were accepted. The median length of antimicrobial treatment was significantly shorter when a recommendation was accepted (0.26 versus 1.78 d; p < 0.001). Refusal of a recommendation was not associated with mortality (odds ratio 1.32; 95% confidence interval, 0.93 to 1.89; p = 0.12). The independent risk factors associated with in-hospital mortality were age, Charlson Comorbidity Index score, admission to a critical care unit, duration between admission and recommendation, and issuance of a recommendation on a carbapenem., Conclusions: The duration of antimicrobial treatment was significantly shorter when a recommendation originating from a CDSS-assisted ASP program was accepted. Future prospective studies including potential residual confounding variables, such as the source of infection or physiological derangement, might help in understanding whether CDSS-assisted ASP will have a direct impact on patient mortality., Competing Interests: JP, LV, MB, and VN are shareholders of Lumed, the company commercializing APSS., (Copyright © 2021, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Published case fatality in blastomycosis patients ranges between 4% and 78%. This study aimed to assess mortality associated with blastomycosis and identify its associated risk factors. We conducted a systematic review of publications related to Blastomyces dermatitidis available in PubMed and Scopus databases. Studies that reported data on blastomycosis mortality and that were published from inception through February 2018 were assessed and included in the analysis. Using the R meta package, a random-effect model meta-analysis was used to calculate pooled and stratified estimates of case-fatality proportions and risk ratios. Of 1553 publications, we included 20 studies reporting on a total of 2820 cases of blastomycosis between 1970 and 2014 and three case series reports with 10, 21, and 36 patients. The mean or median ages ranged from 28 to 59 years. Mortality was defined as attributable mortality caused by blastomycosis in 13 studies. Among 14 studies with a standard error ≤0.05, the overall pooled mortality was 6.6% (95% confidence interval [CI], 4.9-8.2) with 57% heterogeneity. The mortality rate was 37% (95% CI, 23-51) in immunocompromised patients and 75% (95% CI, 53-96) in patients who developed an acute respiratory distress syndrome (ARDS) (n = 3 studies each). ARDS was the only identified risk factor in general patients (risk ratio = 10.2). The overall mortality was significantly higher in studies involving immunocompromised patients and ARDS patients. Our analysis showed considerable heterogeneity among studies. Inconsistent mortality definitions may have contributed to the observed heterogeneity. Further research is needed to assess potential risk factors for mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)