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Chastre J, Wolff M, Fagon J, et al. Comparison of 8 vs 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults: A Randomized Trial. JAMA. 2003;290(19):2588–2598. doi:10.1001/jama.290.19.2588
Author Affiliations: Service de RÉanimation MÉdicale, Hôpital PitiÉ-Salpêtrière, AP-HP (Dr Chastre), Service de RÉanimation MÉdicale, Hôpital Bichat-Claude-Bernard, AP-HP (Dr Wolff), Service de RÉanimation MÉdicale, Hôpital EuropÉen Georges-Pompidou, AP-HP (Dr Fagon), DÉpartement de Biostatistique et Informatique MÉdicale, Hôpital Saint-Louis, AP-HP (Dr Chevret), and Service de RÉanimation, Hôpital des Diaconesses, Paris (Dr Thomas); Service de RÉanimation MÉdicale, Hôpital Kremlin-Bicêtre, AP-HP, Le Kremlin-Bicêtre (Dr Wermert); Service de RÉanimation, Hôpital Les Audaries, La-Roche-sur-Yon (Dr Clementi); Service de RÉanimation MÉdicale, Hôpital Raymond-PoincarÉ, AP-HP, Garches (Dr Gonzalez); DÉpartement d'AnesthÉsie et de RÉanimation, CHU de Rouen, Rouen (Dr Jusserand); Service de RÉanimation MÉdicale, CHU d'Angers, Angers (Dr Asfar); Service de RÉanimation, Hôpital Courcouronne, Évry (Dr Perrin); Service de RÉanimation MÉdicale, Hôpital Saint-Louis, AP-HP, Paris (Dr Fieux); and DÉpartement d'AnesthÉsie et de RÉanimation, CHU de Montpellier, Montpellier (Dr Aubas), France.
Caring for the Critically Ill Patient Section Editor: Deborah J. Cook, MD, Consulting Editor, JAMA.
Context 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
Objective To determine whether 8 days is as effective as 15 days of antibiotic
treatment of patients with microbiologically proven VAP.
Design, Setting, and Participants 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.
Intervention 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
Main Outcome Measures 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.
Results 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).
Conclusions 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
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