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TOPLINE:

Among hospitalized patients with community-acquired pneumonia, those treated with azithromycin plus beta-lactams had lower in-hospital mortality and mortality rates at 30 and 90 days post-admission than those receiving doxycycline plus beta-lactams.

METHODOLOGY:

• Researchers conducted a retrospective matched cohort study to compare mortality outcomes between patients hospitalized with community-acquired pneumonia treated with azithromycin and those treated with doxycycline, each in combination with beta-lactams.
• They enrolled 8492 patients (median age, 73 years; 54.3% men) who received azithromycin or doxycycline for at least 48 hours.
• Patients treated with doxycycline (n = 2671) were matched 1:1 with patients treated with azithromycin based on specific comorbidities, recent immunosuppressant use, and the pneumonia severity index.
• The primary outcome was mortality, assessed at hospital discharge and at 30 and 90 days post-admission; the secondary outcome was the number of hospital-free days within 28 days of admission.

TAKEAWAY:

• The in-hospital mortality rates were significantly lower in the azithromycin group than in the doxycycline group (odds ratio, 0.71; P = .005).
• Treatment with azithromycin was associated with reduced 30-day mortality (hazard ratio [HR], 0.85; P = .041) and 90-day mortality (HR, 0.83; P = .005) compared with treatment with doxycycline.
• Patients receiving azithromycin had significantly more hospital-free days than those receiving doxycycline (adjusted estimate, 1.37; P < .001).
• Among patients who did not require ICU admission within 24 hours of hospitalization, azithromycin improved 90-day survival compared with doxycycline (adjusted HR, 0.85; P = .007).

IN PRACTICE:

“Given that we found a difference in clinical outcomes between azithromycin vs doxycycline with beta-lactam therapy, our observational study suggests a potential benefit with using azithromycin for CAP [community-acquired pneumonia] treatment in contrast to the limited evidence available,” the authors wrote.

SOURCE:

This study was led by Yewande Odeyemi, MBBS, MS, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota. It was published online on May 16, 2025, in Clinical Infectious Diseases.

LIMITATIONS:

This study did not investigate the possible effects of specific beta-lactam antibiotics. It also did not assess the specific causes of community-acquired pneumonia, preventing the evaluation of the appropriateness of antibiotic treatments or the impact of atypical organisms. Additionally, other therapies or interventions were not considered, and outcomes were restricted to all-cause mortality.

DISCLOSURES:

This study did not receive any funding. One author reported receiving grant support from the National Institutes of Health. Another author reported receiving consulting fees from Wolters Kluwer and support for a speaking engagement from the American Society of Nephrology. The other authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.