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To evaluate a clinical guideline for the treatment of ventilator-associated pneumonia.Prospective before-and-after study design.A medical intensive care unit from a university-affiliated, urban teaching hospital.Between April 1999 and January 2000, 102 patients were prospectively evaluated.Prospective patient surveillance, data collection, and implementation of an antimicrobial guideline for the treatment of ventilator-associated pneumonia.The main outcome evaluated was the initial administration of adequate antimicrobial treatment as determined by respiratory tract cultures. Secondary outcomes evaluated included the duration of antimicrobial treatment for ventilator-associated pneumonia, hospital mortality, intensive care unit and hospital lengths of stay, and the occurrence of a second episode of ventilator-associated pneumonia. Fifty consecutive patients with ventilator-associated pneumonia were evaluated in the before period and 52 consecutive patients with ventilator-associated pneumonia were evaluated in the after period. Severity of illness using Acute Physiology and Chronic Health Evaluation II (25.8 ± 5.7 vs. 25.4 ± 8.1, p = .798) and the clinical pulmonary infection scores (6.6 ± 1.0 vs. 6.9 ± 1.2, p = .105) were similar for patients during the two treatment periods. The initial administration of adequate antimicrobial treatment was statistically greater during the after period compared with the before period (94.2% vs. 48.0%, p < .001). The duration of antimicrobial treatment was statistically shorter during the after period compared with the before period (8.6 ± 5.1 days vs. 14.8 ± 8.1 days, p < .001). A second episode of ventilator-associated pneumonia occurred statistically less often among patients in the after period (7.7% vs. 24.0%, p = .030).The application of a clinical guideline for the treatment of ventilator-associated pneumonia can increase the initial administration of adequate antimicrobial treatment and decrease the overall duration of antibiotic treatment. These findings suggest that similar types of guidelines employing local microbiological data can be used to improve overall antibiotic utilization for the treatment of ventilator-associated pneumonia.