Azithromycin Linked to Lower Mortality Than Doxycycline in Pneumonia, finds research

This retrospective observational study analyzed 8492 adult patients diagnosed with community-acquired pneumonia and admitted to Mayo Clinic hospitals over a 4-year period. Patients were included if they were treated with either azithromycin (n = 5810) or doxycycline (n = 2682) in combination with a beta-lactam antibiotic. Those who received both macrolides and tetracyclines concurrently, or who had been on either drug as a chronic therapy before admission, were excluded to minimize bias.

To provide a balanced comparison, one-to-one matching on a number of comorbidities and risk factors such as congestive heart failure, coronary artery disease, COPD, HIV infection, recent immunosuppressant use, and Pneumonia Severity Index class was utilized. The cohort of 2671 patients in both groups resulted after matching.

Key Results

• The main outcome of the study was mortality, both in-hospital and at 90 days. The researchers established that in-hospital mortality was lower for the azithromycin group than for the doxycycline group.

• The odds ratio (OR) for in-hospital mortality with azithromycin was 0.71 (95% Confidence Interval [CI]: 0.56–0.90), representing a 29% decrease in odds of mortality compared with doxycycline.

• In determining 90-day mortality, the hazard ratio (HR) for azithromycin was 0.83 (95% CI: 0.73–0.95), once more demonstrating a significant survival advantage.

• Furthermore, hospital-free days, a marker of time alive and out of the hospital, were greater in the azithromycin arm, with an adjusted estimate of 1.37 days (95% CI: 0.99–1.74).

The research highlights the important issue regarding pneumonia treatment: although doxycycline is usually suggested as an alternative because of cost, availability for oral administration, and resistance considerations, it might not be as valuable for hospitalized patients clinically as azithromycin, especially when used in combination with beta-lactam antibiotics. Better outcomes with azithromycin validate its retention as part of guideline-directed combination therapy for CAP, particularly in those at greater risk of complications.

This study authors concluded that among hospitalized patients with CAP, azithromycin plus a beta-lactam was associated with substantially reduced mortality and increased hospital-free days as compared to doxycycline regimens. These results further support the use of azithromycin in CAP treatment guidelines and imply that doxycycline, though still an option, may not provide equivalent benefit to hospitalized patients.

Reference:

Yewande Odeyemi, Aysun Tekin, Caitlin Schanz, Diana Schreier, Kristin Cole, Ognjen Gajic, Erin Barreto, Comparative effectiveness of azithromycin versus doxycycline in hospitalized patients with community acquired pneumonia treated with beta-lactams: A multicenter matched cohort study, Clinical Infectious Diseases, 2025;, ciaf252, https://doi.org/10.1093/cid/ciaf252