Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment

PLoS One. 2012;7(8):e41290. doi: 10.1371/journal.pone.0041290. Epub 2012 Aug 31.

Abstract

Purpose: The optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition. Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria.

Objective: To demonstrate that 2 different antibiotic treatment durations (8 versus 15 days) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia.

Methods: Randomized, prospective, open, multicenter trial carried out from 1998 to 2002.

Measurements: The primary endpoint was the clinical cure rate at day 21. The mortality rate was evaluated on days 21 and 90.

Results: 225 patients were included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference = 0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and odds ratio were [-8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into account the limits of equivalence (10% for difference and 2.25 for odds ratio), the objective of demonstrative equivalence between the 2 treatment durations was fulfilled. Although the rate of secondary infection was greater in the 8 day than the 15 day cohort, the number of days of antibiotic treatment remained lower in the 8 day cohort. There was no difference in mortality rate between the 2 groups on days 21 and 90.

Conclusion: Our results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients.

Trial registration: ClinicalTrials.gov NCT01559753.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Bronchoalveolar Lavage
  • Cohort Studies
  • Critical Care / methods
  • Cross Infection / etiology
  • Drug Administration Schedule
  • Drug Resistance, Bacterial
  • Female
  • Humans
  • Intensive Care Units
  • Intubation
  • Male
  • Middle Aged
  • Odds Ratio
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Prospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents

Associated data

  • ClinicalTrials.gov/NCT01559753

Grants and funding

French Ministry of Health (Programme hospitalier de recherche clinique), SRLF (Societe de Reanimation de Langue Francaise), Glaxo and Beecham Laboratory. The funders had no role in study desig, data collection and analysis, decision to publish, or preparation of the manuscript.