A single dose of the broad-spectrum antibiotic azithromycin didn't change the proportion of US COVID-19 patients reporting symptoms by 14 days, finds a randomized, controlled trial published late last week in JAMA.
The study, led by University of California at San Francisco (UCSF) researchers, involved assigning 263 non-hospitalized adult COVID-19 patients to either a 1.2-gram dose of oral azithromycin (171) or a placebo (92) from May 2020 to March 2021.
Participants, who had tested positive for COVID-19 within the past 7 days, were followed for as many as 21 days to gauge whether the antibiotic would prevent disease progression by 14 days. Most patients had symptoms at baseline.
There was no significant difference in the proportion of participants reporting no symptoms by 14 days (50% each), regardless of age. Differences between the two groups, however, were significant in terms of several outcomes.
Five participants in the azithromycin group were hospitalized by day 21, compared with zero among placebo recipients (prevalence difference, 4%), a significant difference that calls for further exploration, the researchers noted. The reasons for hospital admission were difficulty breathing (2 patients), pneumonia (1), low oxygen level (1), and severe abdominal pain (1).
Similarly, 14% of azithromycin recipients reported visiting an emergency department or urgent care facility by day 21, compared with 3% of those given a placebo.
More participants in the azithromycin group reported gastrointestinal distress by day 3 than in the placebo group, including diarrhea (41% vs 17%), abdominal pain (17% vs 1%), and nausea (22% vs 10%). No severe adverse events or deaths were reported in either group.
Median participant age was 43 years, 66% were women, 57% were White, 29% were Latino or Hispanic, and 76% completed the trial. The study's data and safety monitoring board ended the study early, on Mar 16, after an interim analysis showed futility.
Threat of antibiotic resistance
Previous randomized clinical trials involving coronavirus inpatients and outpatients haven't identified a benefit of azithromycin in the treatment of COVID-19, regardless of whether it is given with or without the antimalarial drug hydroxychloroquine, the researchers noted.
In a UCSF news release, lead study author Catherine Oldenburg, ScD, MPH, said that the findings don't support the routine treatment of COVID-19 outpatients with azithromycin, an inexpensive antibiotic broadly used in coronavirus patients in the United States and abroad. "The hypothesis is that it has anti-inflammatory properties that may help prevent progression if treated early in the disease," she said. "We did not find this to be the case."
Oldenburg noted that most previous trials on azithromycin as a treatment for COVID-19 involved severely ill hospital patients. "Our paper is one of the first placebo-controlled studies showing no role for azithromycin in outpatients," she said.
Indeed, the researchers said that overuse of antimicrobial drugs like azithromycin in the treatment of COVID-19 could lead to antibiotic resistance. "Widespread use of azithromycin for COVID-19 in the absence of a clear bacterial indication may contribute to resistance selection," they wrote.