Antimicrobial use in COVID-19 patients in the first phase of the SARS-CoV-2 pandemic: Rapid review and evidence synthesis

Background: As the numbers of people with COVID-19 continue to increase globally, concerns have been raised regarding the widespread use of antibiotics for the treatment of COVID-19 patients and its consequences for antimicrobial resistance during the pandemic and beyond. The scale and determinants of antibiotic use in the early phase of the pandemic, and whether antibiotic prescribing is beneficial to treatment effectiveness in COVID-19 patients, are still unknown. Unwarranted treatment of this viral infection with antibiotics may exacerbate the problem of antibiotic resistance, while antibiotic resistance may render presumptive treatment of secondary infections in COVID-19 patients ineffective. Methods: This rapid review was undertaken to identify studies reporting antimicrobial use in the treatment of hospitalised COVID-19 patients. The review was conducted to comply with PRISMA guidelines for Scoping Reviews (http://www.prisma-statement.org/Extensions/ScopingReviews) and the protocol was registered with the Open Science Framework (OSF): http://osf.io/vp6t5. The following databases: Web of Science, EMBASE, PubMed, CNKI & VIP were searched to identify the relevant studies from 1 Dec 2019 up to 15 June 2020; no limits were set on the language or the country where studies were conducted. The search terms used were: ((Covid-19 or SARS-CoV-2 or Coronavirus disease 2019 or severe acute respiratory syndrome coronavirus-2) and ((antibiotic prescribing or antibiotic use or antibiotic*) or antimicrobial* or antimicrobial therapy or antimicrobial resistance or antimicrobial stewardship)). A total of 1216 records were identified through database searching and 118 clinical studies met the inclusion criteria and were taken into data extraction. A bespoke data extraction form was developed and validated through two independent, duplicate extraction of data from five Records. As all the included studies were descriptive in nature, we conducted descriptive synthesis of data and reported pooled estimates such as mean, percentage and frequency. We created a series of scenarios to capture the range of rationales for antibiotic prescribing presented in the included studies. Results: Our results show that during the early phase of the pandemic, 8501 out of 10 329 COVID-19 patients (82.3%) were prescribed antibiotics; antibiotics were prescribed for COVID-19 patients regardless of reported severity, with a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The top five frequently prescribed antibiotics for hospitalised COVID-19 patients were azithromycin (28.0 % of studies), ceftriaxone (17.8%), moxifloxacin (14.4%), meropenem (14.4%) and piperacillin/tazobactam (12.7%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs 41.9 % for patients with mild or moderate illness and those with severe or critical illness respectively. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs 13.1%), higher discharge rates (80.9% vs 69.3%) and shorter length of hospital of stay (9.3 days vs 12.2 days). Only 9.7% of patients in our included studies were reported to have secondary infections. Conclusions: Antibiotics were prescribed indiscriminately for hospitalised COVID-19 patients regardless of severity of illness during the early phase of the pandemic. COVID-19 related concerns and lack of knowledge drove a large proportion of antibiotic use without specific clinical justification. Although we are still in the midst of the pandemic, the goals of antimicrobial stewardship should remain unchanged for the treatment of COVID-19 patients.