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

Gilles Capellier , Hélène Mockly , Claire Charpentier , Djillali Annane (1, 2) , Gilles Blasco (3) , Thibault Desmettre (4) , Antoine Roch (5, 6) , Christophe Faisy (7) , Joel Cousson , Samuel Limat (3) , Mariette Mercier (8) , Laurent Papazian (5, 6)

1 CIT-IT Garches
2 Hôpital Raymond Poincaré [AP-HP]
3 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
4 LCE - Laboratoire Chrono-environnement (UMR 6249)
5 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
6 Service de Réanimation des Détresses Respiratoires et Infections Sévères
7 Service de soins intensifs
8 CEF2P / CARCINO - Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181)

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.

Mots clés: Antibiotics; Pneumonia; Bacterial pathogens; Death rates; Intensive care units; Respiratory infections; Enterococcus infections; Intubation

Domaines: Sciences du Vivant [q-bio]

Gilles Capellier, Hélène Mockly, Claire Charpentier, Djillali Annane, Gilles Blasco, et al.. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS ONE, 2012, 7 (8), pp.e41290. ⟨10.1371/journal.pone.0041290⟩. ⟨hal-00825706⟩