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Am Fam Physician. 2022;105(3):237-238

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Clinical Question

Are antibiotics effective in treating patients with COVID-19?

Evidence-Based Answer

Azithromycin (Zithromax) is the most consistently studied antibiotic for use in treating patients infected with the SARS-CoV-2 virus; it does not improve mortality after 28 days or affect the clinical course for hospitalized adults with COVID-19.1 (Strength of Recommendation [SOR]: A, consistent and good-quality patient-oriented evidence.)

In outpatient adults with asymptomatic or mild COVID-19, azithromycin does not reduce mortality, risk of hospitalization, or disease progression.1 (SOR: B, inconsistent evidence or evidence from methodologically limited trials.)

Practice Pointers

Despite international efforts to contain the spread of the SARS-CoV-2 virus, as of December 2021 the pandemic has resulted in more than 260 million infections and more than 5.3 million deaths worldwide.2 Treatment of COVID-19 depends on disease severity and patient setting, and the ongoing search for safe, effective, and accessible treatment options continues. Antibiotics such as macrolides are a particular research focus, given their potential antiviral and anti-inflammatory properties.

This Cochrane review involved 11 randomized controlled trials and 11,281 patients.1 Seven studies included inpatients (not further defined but designated as patients with moderate to severe SARS-CoV-2 infection), and four studies investigated outpatients (designated as patients with asymptomatic or mild SARS-CoV-2 infection). All of the included studies compared azithromycin with placebo, standard of care, or another antibiotic as a direct therapy against COVID-19. Other antibiotics currently under investigation include doxycycline, clarithromycin (Biaxin), and lincomycin (Lincocin), but the data on these or any other antibiotics were insufficient to include in the review. About half of the study results included in the review were rated as having a “low risk of bias” and the other half as “some concerns for the overall risk of bias.”

Among inpatients with moderate to severe COVID-19, the authors found no significant difference with azithromycin use on all-cause mortality or improvement of clinical status at 28 days of follow-up. Regarding risks, no adverse events (including cardiac arrhythmias) occurred during the study period, and there was no increased risk of serious adverse events.

Among outpatients with asymptomatic or mild COVID-19, the authors found no evidence that azithromycin improved all-cause mortality, decreased hospitalization rates at 28 days of follow-up, or resolved symptoms by 14 days of follow-up. No outpatient studies reported any adverse events or cardiac arrhythmias within the follow-up time frame.

Antibiotic overuse and resulting antimicrobial resistance predate the pandemic as a global health threat.3 Specifically, macrolides have a high resistance potential and have been identified as key targets of stewardship and monitoring to reduce antibiotic resistance.4 With little evidence to support the effectiveness of azithromycin against the SARS-CoV-2 virus, family physicians should not routinely prescribe it for patients with COVID-19.

The practice recommendations in this activity are available at http://www.cochrane.org/CD015025.

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These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.

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