Abstract Objective: To determine if hospital characteristics were associated with rates of healthcare-associated (HA) viral respiratory infections (VRIs) in a large Canadian acute care hospital network. Design: Survey of hospital characteristics and prospective surveillance of HA-VRI. Setting: The Canadian Nosocomial Infection Surveillance Program is a sentinel surveillance system with 89 hospitals participating in adult and pediatric VRI surveillance. Patients Patients with laboratory confirmed infection from SARS-CoV-2, Influenza A/B or RSV associated with their hospitalization from participating hospitals between January 1-December 31, 2024. Methods: A 15-item survey was distributed to hospitals to collect information on hospital infrastructure, infection prevention and control practices, and occupational health measures for healthcare workers. HA-VRI rates/10,000 patient-days were analyzed alongside survey responses using univariable and multivariable negative binomial regression models in R to determine associations. Hospitals without case data were excluded. Results: Of 89 hospitals, 93% (n = 83) responded to the survey, with 79 included in the analysis. The national HA-VRI rate was 8.15/10,000 patient-days. Pediatric hospitals had a 56% lower HA-VRI rate than adult/mixed hospitals ( P < .001) that increased with the exclusion of SARS-CoV-2. Each 10% increase in the percentage of single-bed rooms corresponded to a 12% reduction in infection rate ( P < .001). Teaching vs. Non-teaching hospitals were associated with a 32% lower HA-VRI rate. Universal masking was not associated with a statistically significant reduction in HA-VRI rates (RR 0.82, 95% CI: 0.56–1.19). Conclusions: In a large surveillance network, lower HA-VRI rates were seen in pediatric hospitals, teaching hospitals, and in hospitals with higher proportions of single-bed rooms.

Importance:The optimal choice of antibiotic prophylaxis in elective colorectal surgery remains uncertain, with most reviews emphasizing timing and route of administration rather than direct comparisons of antibiotic classes. Objective:To compare the outcomes associated with different antibiotic classes and class combinations administered within 24 hours before elective colorectal surgery. Data Sources:MEDLINE, Embase, Cochrane Central, and Scopus were searched from inception to July 17, 2025. Study Selection:Eligible studies were randomized clinical trials that enrolled adult patients undergoing elective colorectal procedures and were required to report on surgical site infection (SSI) within 30 days of surgery. Data Extraction and Synthesis:Data on SSIs, adverse events, all-cause mortality, and length of hospital stay were extracted when available by 2 independent reviewers. A frequentist random-effects model was used for network meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses, Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. Main Outcomes and Measures:The primary outcome was risk of SSI; secondary outcomes were 30-day mortality, adverse events, and length of hospital stay. Risk ratios (RRs) with 95% CIs were calculated for binary outcomes, and mean differences (MDs) with SDs were calculated for continuous outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Findings:A total of 105 randomized clinical trials involving 18 273 patients were included. The network included 32 distinct antibiotic nodes defined by antimicrobial class or combination. High to moderate certainty of evidence indicated that, compared with placebo or no antibiotic, several regimens were associated with reduced the risk of SSI. Regimens including broad-spectrum penicillin (RR, 0.26; 95% CI, 0.16-0.42), third-generation cephalosporins (RR, 0.27; 95% CI, 0.16-0.45), a combination of metronidazole and second-generation cephalosporins (RR, 0.27; 95% CI, 0.17-0.44), and tetracyclines (RR, 0.32; 95% CI, 0.20-0.53) were all associated with significant reductions. The antibiotics associated with a significant decrease in mortality compared with placebo were broad-spectrum penicillin (RR, 0.21; 95% CI, 0.05-0.90) and a combination of fluoroquinolones and penicillins (RR, 0.14; 95% CI, 0.03-0.79). No significant differences were observed between antibiotic classes regarding hospital length of stay or adverse events. The certainty of evidence ranged from very low to moderate across outcomes. Conclusions and Relevance:In this systematic review and network meta-analysis, several antibiotic regimens were associated with substantially reduced risk of SSIs after elective colorectal surgery compared with placebo. Broad-spectrum penicillins had the most consistent benefits, with moderate-certainty evidence supporting reductions in risk of both SSI and mortality.

BackgroundRetention in HIV care is essential for achieving optimal health outcomes and extending life expectancy among people living with HIV. However, socioeconomic challenges frequently hinder consistent engagement in care. Virtual care offers a potential solution by enhancing timely access to HIV services and addressing these barriers.ObjectivesWe aimed to examine the association between socioeconomic factors and the use of virtual care among people living with HIV (PLHIV) in a clinical cohort in Ontario, Canada.MethodsWe analyzed 2022 data from the Ontario HIV Treatment Network Cohort Study (OCS), coinciding with the initial rollout of virtual care. The OCS is a multi-site cohort comprising patients from 15 HIV clinics, with data obtained from medical charts, interviews, and linkage to provincial public health lab (PHOL) records for viral load testing. We employed multinomial logistic regression to identify predictors of care mode: virtual, in-person, or a hybrid (virtual and in-person).ResultsThe study included 1,930 participants. Of these, 19% (n = 367) received virtual care, 45.6% (n = 900) received in-person care, and 34.3% (n = 663) accessed hybrid care services. The median participant age was 55 years [Q1; Q3: 45; 62], and 78% (n = 1,131) identified as men who have sex with men (MSM). Compared to Toronto residents, individuals living in Southwestern Ontario had higher odds of using virtual care (adjusted OR (AOR) 1.67, 95% CI: 1.13, 2.47). Conversely, females (AOR = 0.59; 95% CI: 0.40, 0.88), heterosexual men (AOR = 0.64; 95% CI: 0.45, 0.92), residents of Eastern Ontario (AOR = 0.42; 95% CI: 0.26, 0.68), individuals with a high school education (AOR = 0.67; 95% CI: 0.46, 0.98), those with an annual gross income of CAD $71,000-90,000 (AOR = 0.59; 95% CI: 0.38, 0.91), and individuals diagnosed with HIV within the last 10 years (AOR = 0.59; 95% CI: 0.39, 0.91) were less likely to use virtual care. Participants experiencing any level of depression were more likely to use hybrid care services.ConclusionVirtual care was introduced during the COVID-19 pandemic to enhance healthcare access in Ontario. Its adoption varied based on socioeconomic and health-related factors in the OCS cohort. Ongoing research is needed to assess these patterns beyond the pandemic context..

Background: Retention in HIV care is associated with higher rates of antiretroviral treatment adherence and viral suppression, as well as lower risk of AIDS-related morbidity and mortality. However, the multidimensional nature of retention complicates measurement standardization, limiting comparability and global evaluation. This study explored how HIV stakeholders define and assess retention, aiming to develop a patient-centred and conceptually robust understanding to inform research and practice. Methods: We conducted a qualitative study using Interpretive Description (ID) methodology, an applied qualitative approach designed to generate practice-relevant knowledge in health research. We purposively sampled 20 stakeholders representing diverse areas of expertise and geographic regions across World Bank country income classifications. We conducted, video-recorded, and transcribed in-depth, semi-structured interviews. Using constant comparative analysis (CCA), we identified recurring, convergent, and contradictory patterns. Results: The analysis identified five overarching themes. The first two, exploratory themes, included: Patient-Centred Understanding of Retention in HIV Care, which captured how stakeholders conceptualized retention in their respective contexts, and Operationalization of Retention Measures, which explored the key components used to measure retention. The next two, explanatory themes, included Purpose-Driven Definitions of Retention, which described how retention measures were selected based on their intended use; and Building Capacity through Shared Understanding and Integrated Action, which emphasized retention as a cyclical, interconnected process dependent on collaboration between patients and health systems. The final, prescriptive theme, Advancements Shaping Retention, reflected stakeholders' shared vision of improving retention through innovations in HIV treatment and technology. Conclusions: The findings suggest that stakeholders operationalize retention measures in line with specific objectives and individual health goals, while remaining attentive to contextual realities. Retention measures should remain flexible and patient-centred, rather than relying on a single rigid standard. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study has received no funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Hamilton Integrated Research Ethics Board approved this study, including all communication protocols (HiREB #16500). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The qualitative data generated during this study are not publicly available due to ethical restrictions and confidentiality agreements with participants. The interview guide is available as supplementary material.

BACKGROUND:Surgical procedures for malignant bone tumors of the lower extremity are associated with a significant risk of surgical site infection (SSI). Little is known about the microbiology and risk factors for resistant SSIs in this population. METHODS:We describe the microbiological and other characteristics and of SSIs, as well as risk factors for antimicrobial resistance against antibiotics used for perioperative prophylaxis in a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial population. The PARITY trial assessed the effects of short-term (24 hour) versus long-term (5-day) postoperative antibiotic prophylaxis on the SSI incidence in orthopedic oncology. RESULTS:SSIs were identified in 96 of 604 patients (15.9%), with ≥1 pathogen isolated in 73 (76.0%). The most common pathogens were coagulase-negative staphylococci (34.4%), Staphylococcus aureus (24.0%), and Enterobacterales (22.9%). The proportions of pathogens with presumed resistance against cephalosporins were similar in the 2 groups (65.9% in the short-term vs 71.9% in the long-term arm; odds ratio [OR], 0.76 [95% confidence interval, .28-2.06]; P = .58). Neutropenia (22.9% vs 4.8%; OR, 5.95 [95% confidence interval, .72-49.45]; P = .06) and initiation of antibiotics >7 days before SSI diagnosis (50.0% vs 34.8%; OR, 1.88 [.68-5.21; P = .22) were numerically but not statistically significantly more common in those with presumed resistance. CONCLUSIONS:SSIs due to pathogens presumably resistant to the systemic or local prophylactic agents used are common in patients undergoing reconstruction for bone tumors. The selection of presumably resistant pathogens is not driven by the duration of antibiotic prophylaxis; however, antibiotic-loaded cement was associated with resistance.

Objectives Despite high diarrheal burden and antibiotic use, C. difficile infection in West Africa is insufficiently studied. This review synthesizes the limited and methodologically diverse evidence on C. difficile in West Africa, summarizing study-level findings on detection, settings, risk factors and strain characteristics to clarify current knowledge gaps and priorities for future research. Methods A systematic literature search was conducted through September 9, 2024, across major global and African databases. The methodological quality, strengths, limitations, and potential sources of bias of included studies were critically evaluated. Due to heterogeneity, findings were synthesized narratively rather than through meta-analysis. Results Across the nine publications from eight studies identified from Nigeria, Ghana, Côte d'Ivoire, and Mali, investigators reported a wide range of findings related to C. difficile detection in both symptomatic and asymptomatic participants. Individual studies also described various participant or clinical characteristics examined within their samples, including demographics, co-infections, antibiotic use, nutritional indicators, and living conditions. Genotyping data, available from only a few studies, showed considerable ribotype diversity, with RT078 detected in a Malian isolate and RT084 most frequently reported in Ghana and Mali. Conclusions The true burden of C. difficile in West Africa remains unknown. Existing evidence comes from a small number of heterogeneous studies conducted in only four countries, providing an insufficient foundation for regional epidemiologic understanding. Collectively, these data underscore major gaps in surveillance and diagnostic capacity; addressing them will require strengthened laboratory infrastructure, increased clinical awareness, and well-designed epidemiological studies to clarify the organism's role and inform appropriate management. Summary This systematic review highlights the rising concern of Clostridioides difficile in West Africa, urging improved diagnostics, clinical awareness, and research to understand its burden and guide effective treatment.

BACKGROUND:Canada has experienced rising rates of bacterial sexually transmitted infections (STIs)-notably syphilis, chlamydia, and gonorrhoea-over the past two decades, especially among gay, bisexual, and other men who have sex with men. Doxycycline pre- and post-exposure prophylaxis (Doxy-PrEP/PEP) has emerged as a potential prevention strategy. However, concerns about antimicrobial resistance (AMR) have prompted further investigation. METHODS:We conducted a systematic review of English-language studies (2013-2023) using PubMed, Embase, Cochrane, and MedRxiv. We included randomized controlled trials (RCTs), cohort, case-control, ecological studies, and systematic reviews that reported on prolonged or recurrent doxycycline use for any indication across all populations. Data were summarized descriptively due to heterogeneity, and risk of bias and GRADE assessments were conducted to rate level of evidence. RESULTS:Sixteen studies across 17 publications met inclusion criteria. Included studies comprised two systematic reviews, eight RCTs, three cohort studies, two cross-sectional studies, and one modeling study. Seven studies assessed tetracycline/doxycycline resistance in STI pathogens and 12 focused on non-STI organisms. Findings were mixed with some studies reporting increased resistance, others minimal or no change. N. gonorrhoeae showed high baseline doxycycline resistance. Evidence on resistance in skin and gut flora was limited and inconsistent, and no clear pattern of co-resistance to other antimicrobials was found. Overall, the quality of evidence was low to very low. CONCLUSION:Evidence on AMR risks from Doxy-PrEP/PEP published up to 2023 was limited and uncertain. Findings are inconsistent and underpowered and emerging evidence could change these conclusions.

Abstract Background Sustained retention in care supports continuous access to antiretroviral therapy, routine clinical monitoring, and long-term viral suppression. Objective To compare the effectiveness of interventions for improving retention in care among people living with HIV (PLHIV). Design Systematic review and network meta-analysis Data sources PubMed, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Library from 1995 to December 2024. Eligibility criteria Randomised controlled trials (RCTs) evaluating interventions to improve retention in care, viral load suppression, or quality of life (QoL) among PLHIV, compared with standard of care (SoC) or other interventions. Data extraction and synthesis Pairs of reviewers independently screened studies, extracted data, and assessed risk of bias using ROBUST-RCT. We conducted a fixed-effect frequentist network meta-analysis and rated interventions categories relative to SoC based on effect estimates effects and the certainty of evidence.. Dichotomous outcomes were summarized as odds ratios (ORs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with 95% CI. Results Eighty-four trials enrolling 107 137 PLHIV evaluated 13 intervention categories. For retention in care, five interventions supported by moderate or high certainty evidence proved superior to SoC: multi-month dispensing (OR 2.02, 95% CI 1.32 to 3.09), task shifting (OR 1.94, 95% CI 1.42 to 2.66), differentiated service delivery (OR 1.47, 95% CI 1.22 to 1.76), behavioural counselling (OR 1.36, 95% CI 1.21 to 1.54), and supportive interventions (OR 1.31, 95% CI 1.11 to 1.55). For viral load suppression, two interventions supported by moderate or high certainty evidence proved superior to SoC: task shifting (OR 2.07, 95% CI 1.25 to 3.43) and behavioural counselling (OR 1.34, 95% CI 1.11 to 1.67). Across outcomes, no intervention demonstrated convincing superiority over other active interventions. Conclusions Among 13 intervention categories, only a subset provided moderate or high-certainty evidence of superiority to the standard of care, and no superiority to other interventions. Persistent evidence gaps for key populations, diverse settings, and long-term outcomes support the need for context-sensitive and patient-centred interventions. Registration PROSPERO CRD42024589177 Strengths and limitations of this study ➢ This systematic review followed Cochrane methods and was reported in accordance with PRISMA-NMA guidelines. ➢ The network meta-analysis integrated direct and indirect evidence to compare multiple intervention categories within a single framework. ➢ Risk of bias and certainty of evidence were assessed using ROBUST-RCT and the GRADE approach for network meta-analysis, respectively. ➢ Some networks were sparse, and limited representation of key populations and long-term follow-up constrained the strength and generalisability of inferences.

BACKGROUND:Given increasing rates of syphilis and shortages of the first-line agent benzathine penicillin, alternative treatment options are needed. This systematic review examined the existing evidence for alternative treatment regimens for infectious syphilis. METHODS:We searched MEDLINE and EMBASE from January 15, 2021 to January 15, 2025, including eligible studies from two previously published systematic reviews. A systematic review with network meta-analysis (NMA) of randomized controlled trials (RCTs) and a meta-analysis of observational studies was conducted when appropriate. RCTs, cohort studies, case-control studies, and cross-sectional studies published in English that included adult and adolescent participants with infectious syphilis comparing two or more treatment regimens for syphilis were eligible. Risk of bias was assessed using the Cochrane RoB2 tool and Newcastle-Ottawa Scale, and a GRADE assessment was performed. RESULTS:Fourteen RCTs and 20 observational studies were identified. All studies defined cure based on serologic plus/minus clinical response. Thirteen RCTs were eligible for the NMA, representing 1623 participants and 10 treatments. Benzathine penicillin, followed by ceftriaxone, and then doxycycline was reported to be superior to benzathine penicillin alone. However, considering the low quality of the evidence and practicalities of this regimen, this should be interpreted with caution. All other comparisons did not show statistically significant differences in cure rates. However, the pooled point estimates were in favor of doxycycline compared with the standard of care in the NMA (OR of 6.88, lower CrI 0.14). The level of evidence was low for RCTs and very low for observational studies. CONCLUSIONS:Despite low-quality evidence, doxycycline is the best-supported alternative to benzathine penicillin for syphilis treatment.

The Canadian Nosocomial Infection Surveillance Program piloted a study assessing inter-rater agreement among a point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use in acute care hospitals across Canada. Results of this study revealed areas for improvement to be considered in future PPS methodology.

Background Retention in HIV care is associated with higher rates of antiretroviral treatment adherence and viral suppression, as well as lower risk of AIDS-related morbidity and mortality. However, the multidimensional nature of retention complicates measurement standardisation, limiting comparability and global evaluation. Objectives This study explored how HIV stakeholders define and assess retention, aiming to develop a patient-centred and conceptually robust understanding to inform research and practice. Methods We conducted a qualitative study using interpretive description methodology, an applied qualitative approach designed to generate practice-relevant knowledge in health research. We purposively sampled 20 stakeholders representing diverse areas of expertise and geographic regions across World Bank country income classifications. We conducted and video-recorded in-depth semistructured interviews and subsequently transcribed them. Using constant comparative analysis, we identified recurring, convergent and contradictory patterns. Results The analysis identified five overarching themes. The first two, exploratory themes, included Patient-Centred Understanding of Retention in HIV Care, which captured how stakeholders conceptualised retention in their respective contexts and Operationalisation of Retention Measures, which explored the key components used to measure retention. The next two explanatory themes, included Purpose-Driven Definitions of Retention, which described how retention measures were selected based on their intended use, and Building Capacity through Shared Understanding and Integrated Action, which emphasised retention as a cyclical, interconnected process dependent on collaboration between patients and health systems. The final, prescriptive theme, Advancements Shaping Retention, reflected stakeholders’ shared vision of improving retention through innovations in HIV treatment and technology. Conclusions The findings suggest that stakeholders operationalise retention measures in line with specific objectives and individual health goals, while remaining attentive to contextual realities. Retention measures should remain flexible and patient-centred, rather than relying on a single rigid standard.

Background:Antibiotics are frequently prescribed for aspiration pneumonia in ICU patients. We sought to determine the proportion of ICU patients treated for aspiration pneumonia who meet the diagnostic criteria. Methods:A retrospective review of electronic medical records was conducted in adult patients who were admitted to one of two intensive care units at an Ontario tertiary care hospital between June 1, 2022, and October 1, 2023. Patients who were exposed to antibiotics were first identified and then systematically assessed using electronic medical records to identify occurrences in which aspiration was suspected and antibiotics were potentially used to treat aspiration pneumonia within 14 days of the aspiration event. For each episode, we assessed whether patients met the criteria for either confirmed or suspected aspiration pneumonia. Factors associated with inappropriate prescribing were determined. Results:Of 497 patients treated with antibiotics, 104 (22.0%) were treated for aspiration pneumonia. More than one-half (67 patients, 64.4%) were categorized as either confirmed or suspected aspiration pneumonia. There were 35.6% cases (37 of 104) in which antibiotic courses were prescribed for aspiration pneumonia without meeting the criteria for confirmed or suspected cases. Factors associated with not meeting criteria included prescribing by attending physicians compared with residents or fellows (OR 1.53 [95% CI 0.63 to 3.67], p = 0.34) and admitting patients from the emergency department compared with other non-ICU areas (OR 1.96 [95% CI 0.86 to 4.65], p = 0.12). Intubation was associated with a higher odds of confirmed or suspected aspiration pneumonia (OR 1.11 [95% CI 0.47 to 2.57], p = 0.81). Conclusions:Inappropriate antibiotic prescribing for aspiration pneumonia remains common in the ICU.

Importance:Hospital-onset bacteremia and fungemia (HOB) is being proposed as a new hospital quality metric for health care-associated infections. There is a lack of data on the ability of HOB to discriminate between hospitals from a large regional perspective. Objective:To describe and compare the HOB rates across hospitals for the province of Ontario in Canada. Design, Setting, and Participants:This population-based retrospective cohort study used ICES Ontario databases. Participants were adult patients admitted to an acute care hospital from 2017 to 2024 in Ontario, Canada. Exposure:Local care processes and practices in different hospitals. Main Outcomes and Measures:HOB was defined as a positive blood culture collected on or after hospital day 4. HOB rates per admission-days were described across hospital sites. A generalized linear mixed-effects model was used to compare variation in HOB rates across hospitals while adjusting for patient and hospital characteristics. Results:At 114 acute-care hospitals in Ontario, Canada, there were 3 325 900 hospital admissions (median [IQR] age, 71 [57-81] years; 1 727 228 female patients [51.9%]). In total, there were 61 452 HOB episodes observed over 29 721 745 admission-days, equal to an overall rate of 2.07 episodes per 1000 admission-days. Across the 114 acute-care hospitals, the HOB rates were 0.39 episodes per 1000 admission-days for the 10th percentile, 0.71 episodes per 1000 admission-days for the 25th percentile, 1.08 episodes per 1000 admission-days for the 50th percentile, 1.68 episodes per 1000 admission-days for the 75th percentile, and 2.27 episodes per 1000 admission-days for the 90th percentile. In a generalized linear mixed-effects model, the random intercept for hospital sites had an SD of 0.36 (95% CI, 0.29-0.42), which corresponded to a rate ratio of 1.43 (95% CI, 1.34-1.52) per 1 SD. Conclusions and Relevance:In this cohort study of 114 hospitals, there was significant variability in hospital HOB rates, suggesting that HOB may be a useful quality metric in discriminating between hospitals.

Abstract Background Longer follow-up periods in clinical trials for S. aureus bacteremia (SAB) may capture unrelated deaths, adding random noise that risks biasing trial results towards the null. Objective To evaluate the timing and infection-relatedness of deaths within a large SAB clinical trial platform. Design Blinded duplicate adjudication of trial deaths using a modified 7-point Likert-Scale. A third reviewer settled disagreements. Setting 37 Canadian hospitals participating in the S. aureus Network Adaptive Platform (SNAP) Trial. Participants 1515 adult patients recruited to SNAP between February 2022 and May 2026. Measurements Timing and relatedness of 90-day deaths categorized as at least possibly SAB-related not likely to be SAB-related. Optimal follow-up cut-off was determined using Youden’s index and graphically. Results 247 deaths occurred; 97 (39.3%) were adjudicated as at least possibly SAB-related and 150 (60.7%) as not likely related. For probably/definitely related deaths, interrater agreement was 85.0% (Gwet’s AC=0.73, substantial); for at least possibly related, it was 77.3% (Gwet’s AC=0.55, moderate). Median survival was significantly shorter for SAB-related deaths (12 vs. 30.5 days; difference: 19 days earlier, 95% CI: 12-26, p<0.0001). Nearly 80% of SAB-related deaths occurred by day 30, whereas 50% of unrelated deaths occurred between days 30 and 90. Youden’s index optimized follow-up at 20.5 days. Limitations Potential for cause-of-death misclassification and data limited to Canadian sites. Conclusion Deaths considered attributable to SAB cluster rapidly within the first month, while later deaths are predominantly unrelated. A 30-day all-cause mortality window may be more appropriate than 90 days for primary mortality outcomes in trials evaluating acute SAB therapies with longer follow up reserved for metastatic infection and recurrence.

BACKGROUND:Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear. METHODS:In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days. RESULTS:This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%). CONCLUSIONS:In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).

QuestionWhich antibiotic prophylaxis regimens are associated with the lowest risk of surgical site infections (SSIs) among patients undergoing elective colorectal surgery?FindingsIn this systematic review and network meta-analysis of 105 randomized clinical trials with 18 273 patients, broad-spectrum penicillins and cephalosporin-based regimens had the strongest associations with reduced risk of SSIs. Regimens including broad-spectrum penicillins were also associated with decreased risk of mortality, but there were no significant differences among regimens with regard to hospital length of stay or adverse events.MeaningIn this study, broad-spectrum penicillins and cephalosporin-based regimens were most strongly associated with SSI prevention, highlighting antibiotic class selection as a key factor in colorectal surgery prophylaxis. This systematic review and network meta-analysis uses data from randomized clinical trials to compare the association of different antibiotic classes and class combinations with clinical and safety outcomes, including surgical-site infection, mortality, adverse events, and length of stay among patients undergoing elective colorectal surgery. ImportanceThe optimal choice of antibiotic prophylaxis in elective colorectal surgery remains uncertain, with most reviews emphasizing timing and route of administration rather than direct comparisons of antibiotic classes.ObjectiveTo compare the outcomes associated with different antibiotic classes and class combinations administered within 24 hours before elective colorectal surgery.Data SourcesMEDLINE, Embase, Cochrane Central, and Scopus were searched from inception to July 17, 2025.Study SelectionEligible studies were randomized clinical trials that enrolled adult patients undergoing elective colorectal procedures and were required to report on surgical site infection (SSI) within 30 days of surgery.Data Extraction and SynthesisData on SSIs, adverse events, all-cause mortality, and length of hospital stay were extracted when available by 2 independent reviewers. A frequentist random-effects model was used for network meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses, Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions.Main Outcomes and MeasuresThe primary outcome was risk of SSI; secondary outcomes were 30-day mortality, adverse events, and length of hospital stay. Risk ratios (RRs) with 95% CIs were calculated for binary outcomes, and mean differences (MDs) with SDs were calculated for continuous outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.FindingsA total of 105 randomized clinical trials involving 18 273 patients were included. The network included 32 distinct antibiotic nodes defined by antimicrobial class or combination. High to moderate certainty of evidence indicated that, compared with placebo or no antibiotic, several regimens were associated with reduced the risk of SSI. Regimens including broad-spectrum penicillin (RR, 0.26; 95% CI, 0.16-0.42), third-generation cephalosporins (RR, 0.27; 95% CI, 0.16-0.45), a combination of metronidazole and second-generation cephalosporins (RR, 0.27; 95% CI, 0.17-0.44), and tetracyclines (RR, 0.32; 95% CI, 0.20-0.53) were all associated with significant reductions. The antibiotics associated with a significant decrease in mortality compared with placebo were broad-spectrum penicillin (RR, 0.21; 95% CI, 0.05-0.90) and a combination of fluoroquinolones and penicillins (RR, 0.14; 95% CI, 0.03-0.79). No significant differences were observed between antibiotic classes regarding hospital length of stay or adverse events. The certainty of evidence ranged from very low to moderate across outcomes.Conclusions and RelevanceIn this systematic review and network meta-analysis, several antibiotic regimens were associated with substantially reduced risk of SSIs after elective colorectal surgery compared with placebo. Broad-spectrum penicillins had the most consistent benefits, with moderate-certainty evidence supporting reductions in risk of both SSI and mortality.

Background Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. Methods We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. Results From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Conclusions Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence

Whether continuous masking prevents healthcare-associated acute respiratory infections (HA-ARI) remains uncertain. We demonstrate that discontinuing continuous masking policies in 18 acute care facilities in Ontario was not associated with an increase in the incidence of HA-ARIs in hospitalized patients, or with ARI outbreak activity over two consecutive ARI seasons.

ImportancePrevious work found that 25% to 30% of randomized clinical trials (RCTs) with protocols approved in 2012 or between 2000 and 2003 were discontinued prematurely, most commonly due to inadequate participant recruitment. To minimize research waste, RCTs should be registered and their results made available. ObjectivesTo assess the fate of RCTs approved by ethics committees in 2016 in terms of nonregistration, discontinuation, and nonpublication, and to examine RCT characteristics associated with discontinuation due to poor recruitment and nonpublication of RCT results. Evidence ReviewAs a prespecified project of the Adherence to SPIRIT Recommendations (ASPIRE) study, this systematic review had access to 347 RCT protocols approved in 2016 by research ethics committees in the UK, Switzerland, Germany, and Canada. Eligible RCTs were defined as prospective studies randomly assigning participants to interventions to study effects on health outcomes. RCTs were excluded that never started, were ongoing at time of follow-up, were duplicates, or were labeled as pilot, feasibility, or phase 1 trials. Key trial characteristics were extracted from the approved trial protocols. In July 2024, pairs of reviewers systematically searched for trial registrations and results publications. When the status of either was unclear, the corresponding ethics committee or the principal investigator was contacted for clarification. FindingsOf 347 included RCTs, 20 (5.8%) were unregistered, 108 (31.1%) were discontinued, most often due to poor recruitment (49 [45.4%]), and 276 (79.5%) made their results publicly available. Results from industry-sponsored trials were more often available than non-industry-sponsored trials (166 of 181 [92.3%] vs 110 of 166 [66.3%]). This difference was attributable to a higher prevalence of industry-sponsored trials that reported results in trial registries (153 of 181 [84.5%]) vs nonindustry RCTs (17 of 166 [10.2%]). Multivariable logistic regression indicated that industry-sponsored trials were less frequently discontinued due to poor recruitment than non-industry-sponsored RCTs (adjusted odds ratio, 0.32 [95% CI, 0.15-0.71]). Conclusions and RelevanceFindings from this systematic review indicated that nonregistration, premature discontinuation due to poor recruitment, and nonpublication of RCT results remained major challenges, especially for non-industry-sponsored trials. To mitigate these challenges, requirements enforced by funders and ethics committees also taking into account legal obligations should be considered and empirically evaluated.