Are antibiotics an effective treatment for COVID-19? A new Cochrane review weighs up the evidence

News

22 Oct

A new Cochrane review published this week takes a closer look at antibiotics as an effective treatment for Covid-19.

The review explores whether antibiotics reduce death, severity of disease, and length of infection in people with COVID-19, and if they have an effect on quality of life or cause unwanted effects.

The review included studies that compared antibiotics to placebo (dummy treatment), no treatment, usual care, another antibiotic, or treatments for COVID-19 that are known to work to some extent, such as remdesivir or dexamethasone. It excluded treatments that we know do not work for COVID-19, such as hydroxychloroquine, or have an unknown influence on the disease.

The review evaluated the effects of antibiotics on people with COVID-19 on:

people dying;
whether people's COVID-19 symptoms got better or worse;
unwanted effects;
heart rhythm problems;
quality of life.

Key findings

The review included 11 studies with 11,281 people that investigated antibiotics to treat COVID-19. All 11 studies investigated azithromycin.

Nine studies (10,807 people) compared azithromycin to no treatment, placebo or usual care alone. Two studies compared azithromycin to another antibiotic: lincomycin (1 study, 24 people) and clarithromycin (1 study, 450 people), however, they did not report data that Cochrane authors could use in this review, so the results apply to azithromycin only.

Seven studies included people with moderate to severe COVID-19 in hospital and four studies included outpatients with mild COVID-19. The studies used different doses of azithromycin and different durations of treatment.

Inpatients with moderate to severe COVID-19

The review found that azithromycin compared to usual care alone, does not lead to more or fewer deaths in the 28 days after treatment (4 studies, 8600 people).

Compared to usual care alone or placebo, azithromycin probably does not:

worsen (1 study, 7311 people) or
improve patients’ condition (3 studies, 8172 people);
increase or decrease serious unwanted events (4 studies, 794 people), and heart rhythm problems (4 studies, 7865 people).

Azithromycin may increase non-serious unwanted effects slightly compared to usual care alone (3 studies, 355 people).

No studies looked at quality of life.

Outpatients with mild COVID-19

Compared to usual care alone or placebo azithromycin may make little or no difference to:

people dying in the 28 days after treatment (3 studies, 876 people);
whether the people's disease worsened in the 28 days after treatment (3 studies, 876 people) or
• whether people's COVID-19 symptoms got better in the 14 days after treatment (1 study, 138 people).

We don't know whether azithromycin compared to usual care alone or placebo increases or decreases serious unwanted effects (2 studies, 454 participants).

No studies reported non-serious unwanted events, heart rhythm problems, or quality of life.

The Cochrane review author team concluded:

We are certain that risk of death in hospitalised COVID-19 patients is not reduced by treatment with azithromycin after 28 days. Further, based on moderate-certainty evidence, patients in the inpatient setting with moderate and severe disease probably do not benefit from azithromycin used as potential antiviral and anti-inflammatory treatment for COVID-19 regarding clinical worsening or improvement. For the outpatient setting, there is currently low-certainty evidence that azithromycin may have no beneficial effect for COVID-19 individuals. There is no evidence from RCTs available for other antibiotics as antiviral and anti-inflammatory treatment of COVID-19.
With accordance to the living approach of this review, we will continually update our search and include eligible trials to fill this evidence gap. However, in relation to the evidence for azithromycin and in the context of antimicrobial resistance, antibiotics should not be used for treatment of COVID-19 outside well-designed RCTs.

Limitations of the evidence

The review found relevant evidence on only one antibiotic, azithromycin, so we do not know the effects of other antibiotics for treating COVID-19. The author team will continue to search for new studies to fill this evidence gap. The evidence to date does not suggest azithromycin is an effective treatment for COVID-19, especially given the danger of antimicrobial resistance. Azithromycin or any other antibiotic should not be used to treat COVID-19 outside well-designed studies.

Cochrane reviewers are very confident in the evidence on azithromycin for COVID-19 inpatients. However, they are less confident in the evidence on azithromycin in outpatients, mainly because there were few studies that also had some flaws, therefore reliable conclusions couldn’t be drawn.

The evidence included in the review is up to date to 14 June 2021.