Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.

BACKGROUND: Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). METHODS: We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. RESULTS: Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. CONCLUSIONS: Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.

Outbreak of carbapenem-resistant enterobacteriaceae containing blaNDM-1, Ontario, Canada.

BACKGROUND: New Delhi metallo-ß-lactamase (NDM) has emerged worldwide in clinically relevant gram-negative bacteria. We report an outbreak of NDM-producing Klebsiella pneumoniae in patients with no prior travel history to endemic regions. METHODS: Five NDM-1-producing K. pneumoniae colonizing and/or clinically infecting patients in a community tertiary hospital were detected between October and November 2011. NDM-1-producing Enterobacteriaceae (K. pneumoniae and Escherichia coli) were clinically and epidemiologically characterized, including susceptibility profiles, molecular typing, and molecular characterization of plasmids and resistant determinants. RESULTS: Five patients were identified carrying NDM-1-producing K. pneumoniae, all of them epidemiologically linked with each other. K. pneumoniae were confirmed to belong to the same clone, exhibiting multidrug-resistant phenotypes. One patient was positive for NDM-1-producing E. coli in blood and E. coli and K. pneumoniae in rectal specimens, both containing the same bla(NDM) plasmid, suggesting horizontal transfer between species in the patient. No environmental sources of these strains were found. Detection of positive isolates directly from rectal specimens allowed the rapid identification and isolation of colonized patients. CONCLUSIONS: We report a NDM-1-producing K. pneumoniae outbreak in Ontario, Canada. Implementation of standard infection control practices, including active screening was able to contain the spread of this organism in the hospital setting. Of concern is the potential loss of a travel history to identify patients that are at high risk of being colonized or infected with this organism and the lack of an accurate, cost-effective test that can be implemented in the hospital setting to identify these multidrug-resistant organisms.

Standard versus combined chemical, mechanical, and heat decontamination of hospital drains harboring carbapenemase-producing organisms (CPOs): A randomized controlled trial.

We sought to determine whether combined chemical, mechanical, and heat cleaning was superior to standard cleaning for the decontamination of 32 sink and shower drains harboring carbapenemase-producing organisms (CPOs). Of 16 intervention drains, 10 (63%) were decontaminated until day 7 versus 1 (5%) of 16 comparator drains (P = .002). Intensive cleaning may be useful if administered repeatedly in drain-associated CPO outbreaks.

Infection prevention and control practices related to carbapenemase-producing Enterobacteriaceae (CPE) in acute-care hospitals in Ontario, Canada.

OBJECTIVE: To determine infection prevention and control (IPAC) practices for carbapenemase-producing Enterobacteriaceae (CPE), an emerging threat, at acute-care hospitals in Ontario, Canada. DESIGN: A descriptive cross-sectional survey. METHODS: We surveyed IPAC directors and managers at all acute-care hospitals in Ontario, Canada, to gather information on IPAC practices related to CPE, including admission screening, other patient screening, environmental testing, use of precautions to prevent transmission, and outbreak management. RESULTS: Of 116 acute-care hospitals, 105 (91%) responded. Admission screening included patients previously colonized or infected with CPE (n = 64, 61%), patients recently hospitalized outside of Canada (Indian subcontinent, n = 62, 59%; other countries, n = 56, 53%), and patients recently hospitalized in Canada (n = 22, 21%). Fifty-one hospitals (49%) screened patients for colonization during an outbreak. Almost all hospitals (n = 101, 96%) used precautions to prevent transmission from patients with CPE colonization or infection; most hospitals (n = 54, 53%) continued precautions indefinitely. Few hospitals (n = 19, 18%) performed environmental cultures. Eight hospitals (8%) reported at least 1 outbreak, and 6 hospitals (6%) reported transmission from sink or shower drains to patients. CONCLUSIONS: Variability in practices may result from lack of evidence and challenges in updating guidelines as evidence emerges. A coordinated approach to slow the emergence of CPE should be considered in our population.