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

Abstract

Summary 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.

Co-Administration of Remdesivir and Azithromycin May Protect against Intensive Care Unit Admission in COVID-19 Pneumonia Requiring Hospitalization: A Real-Life Observational Study

“…In the earliest phases of the COVID-19 pandemic, the use of azithromycin has also been proposed as a therapeutical option for its potential antiviral and anti-inflammatory effects shown in vitro [ 16 ]. Trials investigating the efficacy of azithromycin alone against severe forms of COVID-19 have produced negative results, and its use is no longer recommended [ 1 , 2 , 17 , 18 ]. However, antibiotic treatment is still part of the clinical management of severe COVID-19, especially in patients showing multiple pulmonary infiltrates on chest imaging or marked elevation of serum inflammation indexes suggesting the presence of a high risk of bacterial superinfection [ 2 , 19 ].…”

What Changed Between the Peak and the Plateau Periods of the First COVID-19 Pandemic Wave? A Multicentric Portuguese Cohort Study in Intensive Care.

“…[53][54][55] Additionally, the use of azithromycin in COVID-19, due to immunomodulatory properties, has shown no clinical bene t in several RCTs. [55][56][57][58][59] Therefore, the routine use of antibiotics in COVID-19 patients is not supported by evidence. 60 Based on the results from the open label Recovery RCT, corticosteroid administration increased signi cantly during the plateau phase but we did not nd any survival bene t in patients so treated.…”

“…Adult patients in this study were mostly male (71.2%) with a median age of 65 [57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] years and arterial hypertension (47.1%) was the most frequent comorbidity. Age group and associated comorbidities and ICU mortality rates are illustrated in Fig.…”

“…1. Approximately one third (32.7%) of patients had no comorbidities and these were younger than the others (63 [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] years vs. 67 [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76], p < 0.001). Patient demographic characteristics and comorbidities are detailed in Table 1 and hospital presenting symptoms are presented in Supplementary table 3.…”

SARS-CoV-2 and Prevotella spp.: friend or foe? A systematic literature review

“…AZM has almost always been used in combination with hydroxychloroquine [120][121][122], nitazoxanide [123], or other drugs [124], which greatly limits the interpretation of its use, during clinical trials. While some randomized patients only take AZM as a treatment, they represent only a small proportion of the studies, and so often nothing can be extrapolated from the conclusions reached [125]. This activity could be explained by their immunemodulatory as well as anti-inflammatory [126] and off-target effects on viral replication.…”