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To prospectively evaluate the performance of the Clinical Pulmonary Infection Score (CPIS) and its components to identify early in the hospital course of ventilator-associated pneumonia (VAP) which patients are responding to therapy.Prospective, multicenter, in a cohort of mechanically ventilated patients.The intensive care unit of six hospitals located in the metropolitan area of Buenos Aires, Argentina.Sixty-three patients, from a cohort of 472 mechanically ventilated patients hospitalized for >72 hrs, had clinical evidence of VAP and bacteriologic confirmation by bronchoalveolar lavage (BAL) or blood cultures.Bronchoscopy with BAL fluid culture and blood cultures after establishing a clinical diagnosis of VAP. All patients received antibiotics, 46 before bronchoscopy and 17 immediately after bronchoscopy.CPIS was measured at 3 days before VAP (VAP-3); at the onset of VAP (VAP); and at 3 (VAP+3), 5 (VAP+5), and 7 (VAP+7) days after onset. CPIS rose from VAP-3 to VAP and then fell progressively in the population as a whole (p < .001), and the fall in CPIS was significant in 31 survivors, but not in 32 nonsurvivors. From the individual components of the CPIS, only the Pao2/Fio2 ratio distinguished survivors from nonsurvivors, beginning at VAP+3. When CPIS was <6 at 3 or 5 days after VAP onset, mortality was lower than in the remaining patients (p = .018). These differences also related to the finding that those receiving adequate therapy had a slight fall in CPIS and a significant increase of Pao2/Fio2 at VAP+3, whereas those getting inadequate therapy did not.Serial measurements of CPIS can define the clinical course of VAP resolution, identifying those with good outcome as early as day 3, and could possibly be of help to define strategies to shorten the duration of therapy.