Comparative effectiveness of azithromycin versus doxycycline in hospitalized patients with community acquired pneumonia treated with beta-lactams: A multicenter matched cohort study

Yewande Odeyemi; Aysun Tekin; Caitlin Schanz; Diana Schreier; Kristin Cole; Ognjen Gajic; Erin Barreto

doi:10.1093/cid/ciaf252

Comparative effectiveness of azithromycin versus doxycycline in hospitalized patients with community acquired pneumonia treated with beta-lactams: A multicenter matched cohort study

Clin Infect Dis. 2025 May 16:ciaf252. doi: 10.1093/cid/ciaf252. Online ahead of print.

Authors

Yewande Odeyemi¹, Aysun Tekin¹, Caitlin Schanz², Diana Schreier², Kristin Cole³, Ognjen Gajic¹, Erin Barreto²

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
² Department of Pharmacy, Mayo Clinic, Rochester, MN.
³ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.

PMID: 40378193
DOI: 10.1093/cid/ciaf252

Abstract

Background: Doxycycline is a frequently used alternative treatment for community-acquired pneumonia in hospitalized patients, but the evidence base is limited. The study aimed to compare outcomes in community-acquired pneumonia patients treated with doxycycline or azithromycin in combination with beta-lactams.

Methods: We evaluated patients with community-acquired pneumonia admitted to Mayo Clinic hospitals from May 2018 to September 2022, treated with either azithromycin or doxycycline in combination with a beta-lactam. Patients who received both antibiotics or were on either as chronic therapy prior to admission were excluded. The primary outcome was mortality. Patients were one-to-one matched according to the presence of congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, human immunodeficiency virus infection, recent immunosuppressant use, and pneumonia severity index class.

Results: Among 8492 patients (5810 for azithromycin, 2682 for doxycycline) 2671 doxycycline-treated patients were matched with azithromycin-treated ones. In hospital mortality was significantly lower in the azithromycin group than in the doxycycline group (odds ratio 0.71; 95% Confidence Interval: 0.56, 0.9), as was 90-day mortality (hazard ratio 0.83= 95% Confidence Interval: 0.73, 0.95). Azithromycin patients also had significantly more hospital free days than those on doxycycline (adjusted estimate=1.37; 95% Confidence Interval: 0.99, 1.74).

Conclusions: Among hospitalized patients with community-acquired pneumonia, azithromycin was associated with a lower mortality and more hospital free days compared to doxycycline in combination with beta-lactams. Randomized controlled trials are needed to assess the effectiveness of each regimen and to compare their potential side effects.

Keywords: Azithromycin; beta-lactam; community-acquired pneumonia; doxycycline.

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