Doxycycline versus azithromycin in combination with beta-lactams for hospitalized community-acquired pneumonia: A propensity score-matched cohort study
In brief
Doxycycline showed no 30-day mortality difference, but sepsis was higher
In a matched cohort of 11,906 patients per group, doxycycline plus a beta-lactam was not linked to a significant difference in 30-day mortality versus azithromycin plus a beta-lactam. Doxycycline was associated with less antibiotic escalation but more 30-day sepsis and slightly higher 180-day mortality; the observational findings do not establish equivalent safety or effectiveness and need prospective confirmation.
- Journal
- Respiratory medicine (Q1)
- Published
- 26 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Timotius Ivan Hariyanto, Akhil Deepak Vatvani, Dania Abu Zahra, Ani Toloraia, Ni Made Mertaniasih
- PMID
- 42933334
- DOI
- 10.1016/j.rmed.2026.109255
Why clinicians should know about it
- Picked for Pulmonary and Respiratory Medicine (paper of the day, 29 October 2026): Large comparative study of hospitalized pneumonia antibiotic regimens
Abstract
BACKGROUND: Azithromycin plus a beta-lactam is a commonly used empiric regimen for hospitalized community-acquired pneumonia (CAP). Concerns about azithromycin resistance and patient-specific safety considerations have increased interest in doxycycline as an alternative; however, comparative effectiveness data for these two regimens remain scarce. METHODS: Using the TriNetX Global Collaborative Network (240 healthcare organizations; data accessed June 14, 2026), we conducted a retrospective cohort study of adults hospitalized with CAP between January 2016 and December 2023. Doxycycline plus beta-lactam recipients were compared with azithromycin plus beta-lactam recipients following 1:1 nearest-neighbor propensity score matching (11,906 patients per group). RESULTS: Thirty-day and 90-day all-cause mortality did not differ significantly between groups (HR: 1.03, 95% CI: 0.95-1.12; and HR: 1.06, 95% CI: 0.98-1.14, respectively), whereas 180-day mortality was modestly but significantly higher in the doxycycline cohort (HR: 1.08, 95% CI: 1.02-1.16; p = 0.014). Doxycycline-based therapy was associated with a consistently lower risk of antibiotic escalation at all time points assessed (RR: 0.59-0.65; p < 0.001). The 30-day risk of incident sepsis was significantly higher with doxycycline (RR: 1.29, 95% CI: 1.03-1.61; p = 0.024). ICU admission, mechanical ventilation, vasopressor use, and Clostridioides difficile infection did not differ significantly between the two groups. CONCLUSIONS: No statistically significant difference in 30-day mortality was detected between doxycycline plus beta-lactams and azithromycin plus beta-lactams. This finding does not establish equivalence or noninferiority. Secondary findings, including 30-day sepsis and 180-day mortality, were exploratory and require confirmation in prospective randomized studies.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.