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Co-infections with SARS-CoV-2 remain relatively rare and there is limited published data on the consequences of these events. We present the case of a 26-year-old man with SARS-CoV-2 and human coronavirus OC43 who had a severe infection resulting in prolonged hospitalization. Consideration of co-infections should be considered in high-risk patients., Competing Interests: R Somayaji received clinical research grants from Cystic Fibrosis Foundation, Canadian Institutes of Health Research, Snyder Institute for Chronic Disease, and the Department of Surgery at the University of Calgary, received educational payments from Vertex Pharmaceuticals, and was a DSMB member on the Oncovir Phase II trial and an advisory board member for Vertex Pharmaceuticals. The other authors have nothing to disclose., (© Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada), 2023.)

Background: Traditionally, bacterial infections have been treated with fixed-duration antibiotic courses; however, some have advocated for individualized durations. It is not known which approach currently predominates., Methods: We conducted a multinational clinical practice survey asking prescribers their approach to treating skin and soft tissue infection (SSTI), community-acquired pneumonia (CAP), pyelonephritis, cholangitis and bloodstream infection (BSI) of an unknown source. The primary outcome was self-reported treatment approach as being fully fixed duration, fixed minimum, fixed maximum, fixed minimum and maximum, or fully individualized durations. Secondary questions explored factors influencing duration of therapy. Multivariable logistic regression with generalized estimating equations was used to examine predictors of use of fully fixed durations., Results: Among 221 respondents, 170 (76.9%) completed the full survey; infectious diseases physicians accounted for 60.6%. Use of a fully fixed duration was least common for SSTI (8.5%) and more common for CAP (28.3%), BSI (29.9%), cholangitis (35.7%) and pyelonephritis (36.3%). Fully individualized therapy, with no fixed minimum or maximum, was used by only a minority: CAP (4.9%), pyelonephritis (5.0%), cholangitis (9.9%), BSI (13.6%) and SSTI (19.5%). In multivariable analyses, a fully fixed duration approach was more common among Canadian respondents [adjusted OR (aOR) 1.76 (95% CI 1.12-2.76)] and for CAP (aOR 4.25, 95% CI 2.53-7.13), cholangitis (aOR 6.01, 95% CI 3.49-10.36), pyelonephritis (aOR 6.08, 95% CI 3.56-10.39) and BSI (aOR 4.49, 95% CI 2.50-8.09) compared with SSTI., Conclusions: There is extensive practice heterogeneity in fixed versus individualized treatment; clinical trials would be helpful to compare these approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: We sought to evaluate the impact of antibiotic selection and duration of therapy on treatment failure in older adults with catheter-associated urinary tract infection (CA-UTI)., Methods: We conducted a population-based cohort study comparing antibiotic treatment options and duration of therapy for non-hospitalized adults aged 66 and older with presumed CA-UTI (defined as an antibiotic prescription and an organism identified in urine culture in a patient with urinary catheterization documented within the prior 90 d). The primary outcome was treatment failure, a composite of repeat urinary antibiotic prescribing, positive blood culture with the same organism, all-cause hospitalization or mortality, within 60 days. We determined the risk of treatment failure accounting for age, sex, comorbidities, and healthcare exposure using log-binomial regression., Results: Of 4,436 CA-UTI patients, 2,709 (61.1%) experienced treatment failure. Compared to a reference of TMP-SMX (61.9% failure), of those treated with fluoroquinolones, 56.3% experienced failure (RR 0.91, 95% CI: 0.85-0.98) and 60.9% of patients treated with nitrofurantoin experienced failure (RR 1.02, 95% CI: 0.94-1.10). Compared to 5-7 days of therapy (treatment failure: 59.4%), 1-4 days was associated with 69.5% failure (RR 1.15, 95% CI: 1.05-1.27), and 8-14 days was associated with a 62.0% failure (RR 1.05, 95% CI: 0.99-1.11)., Conclusions: Although most treatment options for CA-UTI have a similar risk of treatment failure, fluoroquinolones, and treatment durations ≥ 5 days in duration appear to be associated with modestly improved clinical outcomes. From a duration of therapy perspective, this study provides reassurance that relatively short courses of 5-7 days may be reasonable for CA-UTI., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Objectives: In this study, we evaluated the clinical outcomes associated with the use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared with the less-bioavailable oral antibiotics (β-lactams) in gram-negative bloodstream infections (BSIs)., Methods: Among hospitalized older adult patients in Ontario, Canada, discharged home on oral treatment for gram-negative BSI between 1 January 2017 and 31 December 2019, we used a matched cohort design to compare outcomes among those receiving highly versus less-bioavailable agents; hard-matching 1:1 on sex, BSI pathogen (Escherichia coli vs. non-E. coli), and infection source (urinary vs. non-urinary/unknown source) along with a propensity score, incorporating specific pathogen, patient, and infection characteristics. The primary outcome was the composite of 90-day all-cause mortality, recurrent BSI with the same pathogen (genus and species), and re-admission to any Ontario hospital., Results: A total of 2012 patients were included in the study (1006 in each bioavailability category). Those who received highly (compared with less) bioavailable antibiotics at discharge had lower rates of the composite outcome (171/1006 [17.0%] vs. 216/1006 [21.5%]), adjusted odds ratio being 0.74 (95% CI, 0.60-0.92). Recurrent BSI at 90 days was the main driver for the composite outcome occurring in 64 (5.4%) and 107 (9.4%) patients of the highly and less-bioavailable groups, respectively (p < 0.001) (adjusted odds ratio, 0.56; 95% CI, 0.40-0.78)., Discussion: Use of highly (compared with less) bioavailable antibiotics at discharge was associated with significantly better clinical outcomes among patients with gram-negative BSIs., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19., Methods: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344)., Findings: We included 148 studies of 362  976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I 2 =95%)., Interpretation: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed., Funding: WHO., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Global estimates suggest millions of deaths annually are associated with antimicrobial resistance (AMR) but these are generated from scarce data on the relative risk of death attributable to drug-resistant versus drug-sensitive infections., Methods: We examined all episodes of E. coli bloodstream infection in Ontario, Canada between 2017 and 2020, and measured 90 day mortality among those with resistant versus sensitive isolates for each of 8 commonly used antibiotic classes and a category of difficult to treat resistance (DTTR). We used multivariable logistic regression to calculate an adjusted odds of mortality associated with AMR, after accounting for patient demographics, comorbidities, and prior healthcare exposure., Findings: Among 14,548 eligible episodes of E. coli bloodstream infection, resistance was most common to aminopenicillins (46.8%), followed by first generation cephalosporins (38.8%), fluoroquinolones (26.5%), sulfonamides (24.1%), third generation cephalosporins (13.8%), aminoglycosides (11.7%), beta-lactam-beta-lactamase-inhibitors (9.1%) and carbapenems (0.2%). Only 18 (0.1%) episodes exhibited DTTR. For each antibiotic class, the unadjusted odds of mortality (OR) were higher among resistant isolates, but after accounting for patient characteristics the adjusted odds (aOR) of mortality were attenuated: aminopenicillins (OR 1.22, 95% CI 1.12-1.33; aOR 1.09, 95% CI 0.99-1.20), first generation cephalosporins (OR 1.24, 95% CI 1.14-1.35; aOR 1.07, 95% CI 0.97-1.18), third generation cephalosporins (OR 1.64, 95% CI 1.47-1.82; aOR 1.29, 95% CI 1.15-1.46), beta-lactam-beta-lactamase-inhibitors (OR 1.69, 95% CI 1.52-1.89, aOR 1.28, 95% CI 1.13-1.45), carbapenems (OR 3.11, 95% CI 1.52-6.34; aOR 2.06, 95% CI 0.91-4.66), sulfonamides (OR 1.19, 95% CI 1.07-1.31, aOR 1.06, 95% CI 0.95-1.18), fluoroquinolones (OR 1.49, 95% CI 1.36-1.64, aOR 1.16, 95% CI 1.05-1.29), aminoglycosides (OR 1.43, 95% CI 1.27-1.62; aOR 1.27, 95% CI 1.11-1.46), and DTTR (OR 3.71, 95% CI 1.46-9.41; aOR 2.58, 95% CI 0.87-7.66)., Interpretation: AMR is associated with substantial increased mortality among patients with E. coli bloodstream infection, particularly for resistance to classes commonly used as empiric treatment. Surveillance for AMR-associated mortality should incorporate adjustment for patient characteristics and prior healthcare utilization., Funding: This work was supported by a project grant from CIHR (grant number 159503). This study was also supported by ICES, which is funded by an annual grant from Ontario Ministry of Health and Long-Term Care (MOHLTC)., Competing Interests: We declare that we have no conflicts of interest., (Crown Copyright © 2022 Published by Elsevier Ltd.)

Aim: Group A streptococcus (GAS) pharyngitis is a common clinical infection with significant morbidity but remains understudied. Materials & methods: We sought to assess the rates of testing and incidence of GAS pharyngitis in Calgary, Alberta based on age and sex. Results: A total of 1,074,154 tests were analyzed (58.8% female, mean age 24.8 years) of which 16.6% were positive. Age-standardized testing and positivity was greatest in the 5-14 years age group and lowest in persons over 75 years. Females had greater rates of testing and positivity throughout. Testing rates (incidence rate ratios: 1.40, 95% CI: 1.39-1.41) and case rates (incidence rate ratios: 1.36, 95% CI: 1.33-1.39) increased over time. Conclusion: Future studies should focus on evaluating disparities in testing and treatment outcomes to optimize the approach to this infection.

Background: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death., Methods: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data., Results: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety., Interpretation: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered., Trial Registration: ClinicalTrials.gov, no. NCT04329611., Competing Interests: Competing interests: Aravind Ganesh reports payments to his institution from the Canadian Institutes of Health Research (CIHR), the Canadian Cardiovascular Society, Alberta Innovates and Campus Alberta Neuroscience; consulting fees from MD Analytics, My Medical Panel, Atheneum, DeepBench and Research on Mind; meetings or travel support from American Academy of Neurology, Association of Indian Neurologists in America, American Heart Association and University of Calgary; and a provisional patent application for a system for patient monitoring and delivery of remote ischemic conditioning or other cuff-based therapies. He is a member of the editorial boards of Neurology: Clinical Practice, Neurology and Stroke. He has stock in SnapDx (patient monitoring and decision support technology), American Health Analytics (AHA Health Ltd.; patient monitoring) and TheRounds.com (physician social network). Bijoy Menon reports grants or contracts from CIHR, the Heart and Stroke Foundation of Canada and Alberta Innovates Health Solutions and patents from the United States Patent and Trademark Office on systems of triage in acute stroke. He is a member of and has stock in Circle NVI. Michael Hill reports that Apotex Pharma provided the drug and placebo for the current trial as an in-kind contribution to the study. He was the main contact with Apotex Pharma and has no other relationship with the company; there were no obligations attached to this donation of drug and placebo., (© 2021 CMA Joule Inc. or its licensors.)