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To determine the pattern of resolution of classic infectious and respiratory variables in patients with ventilator-associated pneumonia (VAP) and appropriate empirical therapy, depending on the presence of acute respiratory distress syndrome (ARDS). A secondary objective was to identify clinical variables that might be useful for monitoring response to therapy.Prospective, observational cohort study.Medical-surgical intensive care unit.Seventy-five episodes of VAP without ARDS were identified and compared with 20 episodes with ARDS at VAP onset. Six episodes were excluded due to in vitro resistance to the initial antibiotic choice and six due to death in the first 72 hrs.None.Resolution of fever, Pao2/Fio2 >250 mm Hg, and white blood cell count in episodes of VAP were present in 73.3%, 74.7%, and 53.3% of patients after 3 days of therapy. Indeed, >50% of episodes with the absence of ARDS presented resolution of fever and Pao2/Fio2 >250 within the first day of therapy. In contrast, resolution of radiologic opacities and clearance of secretions (median of 14 and 6 days of resolution) were late events. In patients with ARDS, resolution of fever remained the earliest variable. However, similar to Pao2/Fio2 250 and white blood cell count, fever showed a significantly worse pattern after 3 days of therapy: 45%, 15% and 25%, respectively. Radiologic resolution was an extremely poor indicator, being present in only 10% of ARDS patients after 15 days of follow-up. Failure to improve after 48 hrs of therapy was documented in 65% of ARDS patients and 14.7% of controls (p < .05).Measures of oxygenation and core temperature can help physicians to individualize and shorten the duration of antibiotic therapy in VAP episodes. ARDS patients with VAP take twice as long to resolve fever, whereas hypoxemia should be ignored in defining resolution in this subset.