Azithromycin Does Not Reduce COVID-19 Hospitalizations or Death Rate

Timothy Hinks, MD

Antibiotic therapy azithromycin has been associated with broad antiviral activity in human viruses such as human rhinovirus, Zika virus, enteroviruses, Ebola virus, and even SARS-CoV-2.

However, a recent study from the UK confirmed that adding azithromycin to standard care treatment of patients with mild-to-moderate COVID-19 diagnosis was not associated with reduced subsequent hospital admissions or death, or duration of hospital stays.

The antibiotic was among those in its drug class to be considered for treatment of the pandemic virus in early 2020, according to investigators led by Timothy Hinks, MD, Wellcome Trust Career Development Fellow, Respiratory Immunology, Nuffield Dept of Medicine.

Azithromycin is inexpensive, safe, and widely accessible, which Hinks and colleagues believed was the reason for its widespread use in clinical practice and trials in the context of COVID-19.

Despite this, various large-scale clinical trials of azithromycin showed no clinical efficacy regarding patient mortality, mechanical ventilation, duration of hospital admission, or outcome scores.

However, the antibiotic did have antiviral and anti-inflammatory properties that were beneficial to early-stage management of various diseases, which prompted researchers to establish whether it also averts disease progression in patients with COVID-19.

The Study

The team studied and ambulatory population of 1192 patients. Patients were recruited into the study from June 3, 2020 to January 29, 2021.

Requirements for eligibility included a clinical diagnosis of highly probable or confirmed COVID-19 infection with symptoms within the past 14 days of the study. Patients were also required to be 18 years or older.

Once the study population was gathered, patients were randomly assigned to either the azithromycin plus standard care or standard care group. The latter used a web-based automated service, and a minimization algorithm was used to ensure balanced allocation among the treatment groups.

The investigators collected data on demographics, medical history, symptoms, risk factors for disease progression, and severity of all patients at baseline. Physical examinations were also performed.

The azithromycin group received 500 mg of the oral, once-daily antibiotic. Patients from both groups received standard care for 14 days in accordance with local guidelines. The use of corticosteroids, immunomodulators, antibiotics and antivirals were permitted after randomization.

Finally, assessments were conducted on days 14 and 28 of the study, and radiology results and clinical notes were observed when necessary.

Results

The investigators studied the proportion of patients with hospital admission or death within 28 days of the study for the primary outcome, as well as hospital admission that focused on respiratory failure and required non-invasive mechanical ventilation or invasive mechanical ventilation or death for the secondary outcome.

The study showed little to no difference in the outcomes of the azithromycin and standard groups. Hinks and colleagues wrote that the primary endpoint of the study was not significantly different.

Additionally, the data gained from unadjusted and fully adjusted analyses showed no significant differences as well, and the peak severity scores of the azithromycin and standard groups were also similar, at 40% and 44% respectively.

Hinks and fellow investigators mentioned that further studies could be published on the subject, but the end results would likely be the same.

“Given the small absolute event rates for the primary outcome in our study, a smaller but clinically relevant effect cannot be entirely ruled out, but would be unlikely to change clinical practice,” investigators wrote. “Nonetheless, this finding, taken together with clear negative results across the disease course from early, low-risk patients to patients admitted to hospital with severe disease, provides strong confirmation that azithromycin is not effective in treating COVID-19.”

The study, “Azithromycin versus standard care in patients with mild-to-moderate CVOID-19 (ATOMIC2): an open-label, randomized trial,” was published online in The Lancet Respiratory Medicine.