Peter Daley

Background: Patients with suspected bloodstream infection often receive broad-spectrum antibiotics with anaerobic activity in the absence of clinical indication for anaerobic coverage. Antianaerobic antibiotics have been linked to adverse clinical outcomes in other populations, potentially by depleting intestinal anaerobes. Methods: We conducted a planned substudy of the multisite BALANCE randomized controlled trial of antibiotic duration for bloodstream infection to assess the impact of antianaerobic antibiotics (receipt from 3 days preindex culture to 7 days postindex) on mortality and gut microbiome composition with metagenomic sequencing in patients without clinical indication for anaerobic coverage who survived to 7 days postindex culture. The primary exposure was receipt of antianaerobic antibiotics from 3 days prior to the index culture to 7 days postindex culture. Results: Among the 2851 eligible patients included in our primary analysis, 2106 (74%) received antianaerobic antibiotics, and 745 (26%) did not. After balancing measured potential confounders through inverse probability of treatment weighting, antianaerobic antibiotics were associated with higher 90-day mortality (OR = 1.41, 95% CI 1.03–1.92, P = .03) and depletion of gut anaerobe relative abundance (fixed effect estimate = −16.59, 95% CI −30.67 to −2.52, P = .02). Increased duration of antianaerobic antibiotics was associated with greater mortality risk and additional gut anaerobe depletion. Conclusions: Antianaerobic antibiotics are associated with increased mortality and gut microbiome disruption in patients with bloodstream infection. Minimizing exposure to antianaerobic antibiotics for bloodstream infection should be further explored in clinical trials as a potential treatment strategy to improve patient outcomes.

Background: Outpatient therapeutics for SARS-CoV-2 remain critical to reducing disease severity, preventing hospitalization, and mitigating long-term complications, yet evidence across trials has been fragmented and evolving. Objective: To systematically identify and evaluate the effectiveness of oral or inhaled pharmaceutical treatments, including repurposed and antiviral therapies, for acute SARS-CoV-2 infection in adult patients managed in outpatient settings. Methods: Comprehensive peer-reviewed searches were conducted in several databases for studies published by March 2024. We included randomized controlled trials evaluating oral or inhaled therapeutics administered to adults with acute SARS-CoV-2 infection in outpatient settings and excluded non-randomized and observational studies. Outcomes of interest included severe clinical outcomes. Random-effects meta-analyses were performed where feasible. Results: A total of 124 randomized controlled trials evaluating 137 therapeutics across 35 countries were included. Most interventions were repurposed agents ( n = 88), with 33 antiviral and three combination regimens. Molnupiravir shortened time to recovery and reduced hospitalization in a subgroup pool of unvaccinated, higher-risk outpatients (OR 0.68, 95% CI 0.52–0.89), although this effect attenuated when mostly vaccinated patients was included (OR 0.83, 95% CI 0.58–1.19). Inhaled budesonide and metformin showed modest or setting-specific benefits, while most repurposed drugs, including fluvoxamine, ivermectin, and hydroxychloroquine, had no consistent clinical impact. Safety profiles were class-typical with no new signals identified. Conclusions: Most repurposed and antiviral therapies evaluated in outpatient COVID-19 trials showed no consistent benefit for severe clinical outcomes. Modest or setting-specific effects were observed for inhaled budesonide, metformin, and molnupiravir, with molnupiravir’s effect on hospitalization most evident in unvaccinated, higher-risk outpatients and unreplicated for mortality. Clinical trial number: Not applicable.

Antimicrobial resistance (AMR) is a growing public health threat in Canada. In 2022, rising resistance was reported among key pathogens, yet national coordination remains inconsistent, with strategies varying widely by province and territory. This study explored AMR-related challenges in healthcare and the impact of the COVID-19 pandemic on AMR efforts in Canada. Using a qualitative design, researchers conducted semi-structured interviews with 59 experts from fields such as microbiology, public health, and industry. Participants were identified through environmental scanning and snowball sampling. Thematic analysis of transcripts revealed major barriers to a unified AMR response, including inconsistent surveillance, fragmented stewardship efforts, and decentralized health systems. According to participating AMR experts, COVID-19 disrupted AMR control by diverting resources and potentially increasing resistance but also led to improvements in infection prevention, public awareness, and health infrastructure. Participants emphasized the need for stronger political commitment, improved surveillance, a One Health approach, and better funded, coordinated stewardship programs. With the publication of the Pan-Canadian Action Plan in 2023, the Canadian federal government has announced changes. However, effectively addressing AMR will require a unified, multisectoral strategy that bridges political, health, and societal efforts across jurisdictions.

Introduction: Prospective audit and feedback (PAF) are an antimicrobial stewardship intervention that reduces use of broad-spectrum antimicrobials among in-patients. The objective of this study was to assess the impact of adherence to PAF recommendations on the duration of broad-spectrum antimicrobials and patient outcomes. Methods: This retrospective cohort study included adult in-patients at two tertiary care hospitals in St. John's, Newfoundland and Labrador Canada. PAF included all prescriptions for piperacillin/tazobactam, meropenem, ertapenem, and imipenem, reviewed by an infectious disease specialist on day 3 of therapy, with recommendations provided in the electronic medical record. The primary outcome was duration of treatment following PAF. Secondary outcomes were time to all-cause mortality, time to readmission, length of stay, and time to Clostridiodes difficile infection. Adherence categories were compared. Results: Of the recommendations, 394 out of 786 (50.1%) were completely followed, 18.3% were partially followed, and 31.6% were not followed. There were no significant differences in adherence category based on patient age ( p = 0.48) or sex ( p = 0.93). Adherence category was associated with a graded reduction in mean duration of target antimicrobial treatment following PAF ( p < 0.001), and length of stay after PAF ( p < 0.05). Adherence category was not associated with mortality (log-rank = 0.58), readmission rate (log-rank p = 0.33), C. difficile DNA (log-rank p = 0.24) or C. difficile toxin (log-rank p = 0.084). Conclusions: Adherence to PAF reduces antimicrobial use and length of stay without creating harms, such as readmission. This shows that PAF can be beneficial, and future research should be tailored to increasing adherence to PAF recommendations.

Despite the provision of a mumps vaccination program in Canada for over three decades, mumps has not reached elimination. Instead, a re-emergence has been observed in vaccinated populations, particularly in young adults. These outbreaks have been almost exclusively due to genotype G infections, a trend that has been seen in other countries with high mumps vaccination rates. To characterize mumps outbreaks in Canada, genomes from samples from Manitoba (n = 209), Newfoundland (n = 25), and Nova Scotia (n = 48) were sequenced and analysed by Bayesian inference. Whole genome sequencing was shown to be highly discriminatory for outbreak investigations compared to traditional Sanger sequencing. The results showed that mumps virus genotype G most likely circulated endemically in Canada and between Canada and the US. Overall, this Canadian outbreak data from different provinces and ancestral strains demonstrates the benefits of molecular genomic data to better characterize mumps outbreaks, but also suggests genomics could further our understanding of the reasons for potential immune escape of mumps genotype G and evolution in highly vaccinated populations. With a possible endemic circulation of mumps genotype G and the remaining risk of new imported cases, increased surveillance and alternative vaccination strategies may be required for Canada to reach the current target for mumps or a future elimination status.

Background: Data that have been reported on antimicrobial use in Newfoundland and Labrador (NL) do not appear to be representative of use at the population level. We sought to use pharmacy network data on prescriptions to describe outpatient antimicrobial use in NL. Methods: We analyzed all outpatient antimicrobial prescriptions dispensed between June 1, 2017, and June 8, 2021, from the provincial pharmacy network database and translated deidentified data into SPSS. We excluded prescriptions for parenteral and topical antimicrobials, antivirals and antifungals. We described antimicrobial use using the prescription rate and defined daily dose (DDD) rate. Results: Overall, we analyzed 1 586 534 prescriptions dispensed to 394 708 people by 3431 prescribers. The rate of antimicrobial use was 741 prescriptions per 1000 population per year (7161 DDD/1000 population/yr). The median duration of prescriptions was 7 (interquartile range 7–10) days. The prescription rate decreased from 867 to 546 per 1000 population per year (−37%) over the study period, and the mean DDD rate decreased from 8387 to 5356 DDD per 1000 population per year (−36.1%). Antimicrobials with the highest DDD rate were amoxicillin (1568 DDD/1000/yr), doxycycline (864 DDD/1000/yr) and ciprofloxacin (633 DDD/1000/yr). Prescribers wrote a mean of 102 (standard deviation 248) prescriptions per year; 3 prescribers wrote more than 2500 prescriptions per year. Overall, 9203 (2.3%) of the 394 708 people in the study population received 4 or more prescriptions per year. Interpretation: The rate of antimicrobial use in NL is lower than previously described in national surveillance data. Potential targets for stewardship intervention include prolonged duration of prescriptions, high-rate prescribers and high-rate patients, but further research is needed to assess the appropriateness of prescriptions according to diagnosis.

Background: Sexually transmitted and blood borne infection (STBBI) testing is recommended for people who are incarcerated (PWAI). We sought to determine the rate of STBBI testing during admissions to provincial correctional institutions in Newfoundland and Labrador (NL). Methods: This retrospective cohort study collected the identification of all admissions records in provincial correctional facilities in NL between July 1, 2020 and June 31, 2021 using the Provincial Corrections Offender Maintenance System database. Admissions to provincial detention centers were excluded. Records were linked with STBBI results, when available, within the electronic medical record (Meditech) using demographics. Testing rates, STBBI positivity rates, and univariate analysis of predictors for STBBI testing were completed. Results: Of the 1,824 admissions identified, 1,716 were available for linkage to laboratory results. Admissions to detention centers ( n = 105) were excluded. Any STBBI test result was available for 72 (4.5%) of admissions. No admission had complete testing for all STBBI. Facility testing rates ranged from 1.9 to 11.2% and 37.5% of STBBI tests had any positive results. Sixteen out of the 21 (76.2%) hepatitis C virus (HCV) antibody positives received HCV RNA testing, and 11/16 (88.8%) were HCV RNA positive. Institution ( p = 0.001) and sex ( p = 0.004) were found to be significant predictors of STBBI testing, while age was not significant ( p = 0.496). Conclusions: STBBI testing rates were low in provincial correctional facilities in NL, and STBBI prevalence, especially for HCV, was high among those tested. Strategies to increase the rate of testing could contribute to STBBI control in corrections facilities.

We conducted a prospective, randomized, unblinded superiority trial of the safety and efficacy of modified reporting of positive urine cultures to improve the appropriateness of treatment for asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) in long-term care facilities (LTCFs). Consecutive positive urine cultures collected from LTCF patients were randomized between standard (identification and susceptibility) or modified (without identification and susceptibility) laboratory reports. Exclusion criteria were current antibiotic treatment, neutropenia, or transfer to acute care. The diagnosis of UTI or ASB was made prospectively. One hundred and sixty-nine urine cultures were considered, 100 were randomized and included in ITT analysis, and 96 were included in PP analysis. Sixty-two out of 100 (62%) patients had ASB [41/62 (66%) treated] and 38/100 (38%) had UTI [35/38 (92%) treated]. The lab was called to report the identification and susceptibility in 31/51 (61%) modified reports. The rate of appropriate treatment was higher in the modified report arm: 31/51 (61%) versus 25/49 (51%) (+10%, P = 0.33). Untreated ASB was higher in the modified report arm: 13/32 (41%) versus 8/30 (27%) (+14%, P = 0.25). There were two deaths (one treated ASB, one untreated ASB) and 15 adverse events in the modified arm. There were no deaths (P = 0.16) and 11 adverse events (P = 0.43) in the standard arm. Three patients with untreated UTI survived. Modified reporting of urine culture improved the appropriateness of treatment by reducing treatment of ASB, but not significantly. Many LTCF prescribers requested standard urine culture reports. Modified reporting may not be suitable for LTCF implementation.

Background: Human immunodeficiency virus infection (HIV) is one of the major health burdens in Nigeria. Delayed HIV diagnosis remains a significant driver of HIV transmission. The risk factors of delayed HIV diagnosis have not been widely studied in Nigeria. This observational study examined demographic risk factors for delayed HIV diagnosis and the trends in the annual total cases of delayed HIV diagnosis in Ibadan, Nigeria. Methods: We examined the data on HIV patients enrolled in care at the University College Hospital’s Antiretroviral Therapy (ART) clinic in Ibadan, Nigeria. Delayed HIV diagnosis was defined as a Cluster of Differentiation 4 (CD4) count of less than 350 cells/mm³ at the time of diagnosis. The association between delayed HIV diagnosis and risk factors was analyzed using logistic regression. The trends in the annual total cases of delayed HIV diagnosis over time were examined. Results: This study included 3458 HIV patients. There were 1993/3458 prevalent cases of delayed HIV diagnosis (57.6%). The risk factors for delayed HIV diagnosis were older age, retirement, marriage separation, never married, and widowed female. The factors that were significantly associated with a low risk of delayed HIV diagnosis were student and tertiary education. There was a progressive decline in the annual cases of delayed HIV diagnosis. Conclusions: Although the cases of delayed HIV diagnosis are still high, they are declining. Human immunodeficiency virus testing should be targeted at populations at risk of delayed diagnosis. Considerable public awareness and education programs about HIV testing may significantly reduce delayed HIV diagnosis in Nigeria.