Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials

Abstract

Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.

Keywords: Covid-19; azithromycin; efficacy; meta-analysis; mortality; safety; systematic review.

FIGURE 1

PRISMA flow chart for study selection

FIGURE 2

Association between AZM use and (a) 28‐day all‐cause mortality; (b) Need for invasive mechanical ventilation; (c) Discharge within the study period effect size is shown for each trial, overall and stratified by the severity. AZM, azithromycin

FIGURE 3

Association between AZM use and length of stay in each trial, overall and according to the severity. AZM, azithromycin; SeTE, standard error for the total effect; TE, total effect (raw difference in medians)

FIGURE 4

Association between AZM use and (a) incidence of arrhythmia and (b) incidence of QTc interval prolongation. AZM, azithromycin; QTC, Q‐T corrected interval