Antibacterial agents used in COVID-19: A systematic review and meta-analysis

Abstract

There have been speculations regarding rise in antimicrobial resistance (AMR) globally owing to indiscriminate antibiotic usage during the COVID-19 pandemic. To curb the menace through decisive policies, it is essential to assess the antibiotics, particularly the antibacterial agents. This systematic review and meta-analysis were performed to assess antibiotic use in COVID-19 patients. A thorough systematic search was undertaken in databases like PubMed, Cochrane library, Google Scholar, World Health Organization (WHO) database and clinicaltrials.gov by two independent reviewers for articles in English published from January 1, 2019 to October 31, 2020. Studies were included if they assessed confirmed COVID-19 cases and mentioned the use of antibiotics. The primary outcome was the proportion of COVID-19 patients subjected to specific antibacterial agents. An attempt to stratify the data based on study settings and disease severity was also performed. Of the total 6012 studies screened, 40 were eligible for qualitative review and 19 for meta-analysis. Specific antibacterial agents were mentioned in 23 studies (57.5%). In the random effect meta-analysis, pooled prevalence of azithromycin use was 24.5% (95% CI 22.9–26.2%) followed by cephalosporins as 26.6% (95% CI 24.9–28.4). None of the studies clearly specified indications for antibiotic use. Ten studies (25%) mentioned empirical use of antibiotics. Bacterial co-infections/secondary infections were documented in four studies with mean prevalence of infection of 1.9% (95% CI 1.2–2.8%). There is lack of data on use of specific antibacterial agents, indications for their use based on severity of infections and microbiological evidence of bacterial co-infections.

Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study

“…Cephalosporin and azithromycin were the most commonly used antibacterial prophylactics and treatment against bacterial coinfections in SARS-CoV-2 patients, but there still lack literature on their exact indications and efficacy [ 36 ]. In addition, these antibiotics with antiviral agents were often used without solid microbiological evidence on bacterial coinfections followed by COVID-19 infections in mild to moderate patients [ 51 ].…”

“…Yet, some other clinical trials related to the new drugs for SARS-CoV-2 are still underway [ 33 ]. The combination of antiviral agents and antibiotics was widely used to treat SARS-CoV-2 patients globally in practice, and some existing studies reported efficacy and safety of antiviral agents in SARS-CoV-2 [ 34 , 35 ], but studies on those of antibiotics with solid clinical results are still lacking despite their wide empirical use [ 36 ]. Thus, here we present our experience on SARS-CoV-2 management with pharmacological therapy based on clinical research.…”

Azithromycin use and outcomes in patients with COVID-19: an observational real-world study

“…Our findings do not support the hypothesis of a protective role of azithromycin in all observed endpoints. Instead, our data outline the concern of potential inappropriate use of this medication, which was empirically prescribed in subjects infected with SARS-CoV-2 during the pandemic period (Gonzalez-Zorn et al, 2021, Sharma et al, 2021, Huang et al, 2020, ECDS 2021. In fact, despite the massive use of antibiotics observed in subjects developing early COVID-19 symptoms (Sharma et al,2021, Khan et al, 2022, several studies have shown that co-infection and secondary bacterial infection occurred only in 3.5%-14.3% of COVID-19 patients (Sharma et al,2021, Lansburry et al, 2020, Langford et al, 2020, Hughes et al, 2020, Chedid et al, 2021, ECDS 2021).…”

“…Since the early phase of virus diffusion, several drug classes have been repurposed as potential candidates for COVID-19 treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and heparins (Perico et al, 2020, Sanders et al, 2020. Among others, azithromycin, a second-generation macrolide, received increasing attention because of its antiviral and immunomodulatory activities (Langford et al, 2021, Abdelmalek et al, 2022, Sharma et al, 2021. A body of evidence on the effect of azithromycin on viral infections such as Zika, rhinovirus and Ebola infection contributed to raise the hypothesis of potential efficacy of azithromycin against SARS-CoV-2 infection resulting from multiple possible mechanisms of action (Bosseboeuf et al, 2018, Madrid et al, 2015, Gielen et al, 2010.…”

Azithromycin Misuse During the COVID-19 Pandemic: A Cross-Sectional Study from Jordan

“…A good number of studies reported high use of antibiotics during COVID-19 on hospitalized and non-hospitalized patients. [20][21][22][23][24][25] These uses were partly due to the clinical care guidelines in some countries. However, Goyal et al reported that out of 393 COVID-19 patients in New York, only 5.6% developed bacteremia without receiving antibiotics.…”