Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial

Clin Microbiol Infect. 2024 Aug;30(8):1020-1028. doi: 10.1016/j.cmi.2024.05.003. Epub 2024 May 9.

Abstract

Objectives: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP).

Methods: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4).

Results: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations.

Discussion: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment.

Trial registration: This trial is registered with ClinicalTrials.gov, NCT01963442.

Keywords: Antibiotics; Community-acquired pneumonia; Failure; Oral route.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / therapeutic use
  • Cephalosporins / administration & dosage
  • Cephalosporins / therapeutic use
  • Community-Acquired Infections* / drug therapy
  • Female
  • Hospitalization*
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / drug therapy
  • Pneumonia, Bacterial / drug therapy
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination
  • Cephalosporins

Associated data

  • ClinicalTrials.gov/NCT01963442