---
title: "Azithromycin versus doxycycline with beta-lactams for hospitalised community-acquired pneumonia: t"
id: "bmj-open-4-azithromycin-versus-doxycycline-in-hospitalised-adult-patients-with-community"
canonical_url: "https://medichelpline.com/clinical-feed/bmj-open-4-azithromycin-versus-doxycycline-in-hospitalised-adult-patients-with-community"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "BMJ Open"
source_url: "http://bmjopen.bmj.com/cgi/content/short/16/7/e118028?rss=1"
published_at: "2026-07-27T13:07:18.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Azithromycin versus doxycycline with beta-lactams for hospitalised community-acquired pneumonia: t
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/bmj-open-4-azithromycin-versus-doxycycline-in-hospitalised-adult-patients-with-community
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** BMJ Open
- **Source URL:** [Original Journal Publication](http://bmjopen.bmj.com/cgi/content/short/16/7/e118028?rss=1)
- **Published At:** 2026-07-27T13:07:18.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This protocol describes a pragmatic, open-label, randomised clinical trial comparing **azithromycin** versus **doxycycline**, each combined with a **beta-lactam**, for adult patients hospitalised with **community-acquired pneumonia (CAP)**. - The trial responds to uncertainty about optimal adjunctive therapy for CAP as pathogens are often unidentified and rising resistance plus safety concerns have prompted more doxycycline use despite limited evidence. - Eligibility includes adults presenting to the emergency department or referred for hospitalisation with a clinical presentation concerning for CAP and a need for inpatient care. - Planned enrolment is 1,120 adults across six hospitals in four states, representing rural, suburban, urban, academic and community settings. - Randomisation is 1:1 and implemented via an electronic health record (EHR)-embedded screening and randomisation tool triggered by clinician orders for azithromycin or doxycycline. - Outcomes will be ascertained pragmatically through EHR-based data retrieval without additional study visits, minimizing trial burden. - The primary outcome is **days alive and out of the hospital through day 28**. Secondary outcomes include oxygen-free days; a composite of need for advanced respiratory support or in-hospital mortality and separate analyses of each component; an ordinal clinical deterioration measure on a prespecified severity scale; and 60- and 180-day mortality. - Safety outcomes are incidence of **Clostridioides difficile** infection and **QT prolongation**. - Analyses follow an intention-to-treat framework with per-protocol sensitivity analyses. The primary comparison will use a stratified van Elteren test, with supportive proportional odds regression and ANCOVA adjusted for key covariates. - The Mayo Clinic IRB approved the protocol with a waiver of written consent; verbal consent will be obtained by the clinician initiating antibiotics (IRB# 24 - 0 06 503). - Results will be disseminated via peer-reviewed publications and international conferences. Trial registration number is NCT07164131.
## Clinical Analysis & Structured Key Points
Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician's orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24 - 0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT07164131 .
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