Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults

TLDR

The optimal duration of antimicrobial treatment for ventilator‑associated pneumonia (VAP) is unknown. The study aimed to determine whether an 8‑day antibiotic course is as effective as a 15‑day course for patients with microbiologically proven VAP. A prospective, randomized, double‑blind trial enrolled 401 VAP patients across 51 French ICUs, assigning 197 to 8 days and 204 to 15 days of antibiotic therapy chosen by treating physicians, with primary outcomes of mortality, infection recurrence, and antibiotic‑free days assessed at 28 days. The 8‑day regimen produced similar mortality, recurrence, and ICU outcomes to the 15‑day regimen, increased antibiotic‑free days, and, except for higher recurrence in nonfermenting gram‑negative bacilli, did not differ in effectiveness, while it also reduced multiresistant pathogen emergence and overall antibiotic use.

Abstract

The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU).To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP.Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002.A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician.Primary outcome measures-death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days-were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis.Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation-free days, the number of organ failure-free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P =.04).Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.