Abstract

Background: Optimal management of patients who are clinically suspected of having ventilator-associated pneumonia remains open to debate. Objective: To evaluate the effect on clinical outcome and antibiotic use of two strategies to diagnose ventilator-associated pneumonia and select initial treatment for this condition. Design: Multicenter, randomized, uncontrolled trial. Setting: 31 intensive care units in France. Patients: 413 patients suspected of having ventilator-associated pneumonia. Intervention: The invasive management strategy was based on direct examination of bronchoscopic protected specimen brush samples or bronchoalveolar lavage samples and their quantitative cultures. The noninvasive ("clinical") management strategy was based on clinical criteria, isolation of microorganisms by nonquantitative analysis of endotracheal aspirates, and clinical practice guidelines. Measurements: Death from any cause, quantification of organ failure, and antibiotic use at 14 and 28 days. Results: Compared with patients who received clinical management, patients who received invasive management had reduced mortality at day 14 (16.2% and 25.8%; difference, −9.6 percentage points [95% CI, −17.4 to −1.8 percentage points]; P = 0.022), decreased mean Sepsis-related Organ Failure Assessment scores at day 3 (6.1 ± 4.0 and 7.0 ± 4.3; P = 0.033) and day 7 (4.9 ± 4.0 and 5.8 ± 4.4; P = 0.043), and decreased antibiotic use (mean number of antibiotic-free days, 5.0 ± 5.1 and 2.2 ± 3.5; P < 0.001). At 28 days, the invasive management group had significantly more antibiotic-free days (11.5 ± 9.0 compared with 7.5 ± 7.6; P < 0.001), and only multivariate analysis showed a significant difference in mortality (hazard ratio, 1.54 [CI, 1.10 to 2.16]; P = 0.01). Conclusions: Compared with a noninvasive management strategy, an invasive management strategy was significantly associated with fewer deaths at 14 days, earlier attenuation of organ dysfunction, and less antibiotic use in patients suspected of having ventilator-associated pneumonia. *For members of the VAP Trial Group, see the Appendix.