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

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.