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Appropriateness of antibiotic therapy is associated with reduction of bacterial load in ventilator-associated pneumonia. C-reactive protein is a valid biochemical surrogate. The objective was to determine the correlation of bacterial load, measured by quantitative tracheal aspirate (QTA), with serum C-reactive protein as an indicator of inflammatory response in episodes of ventilator-associated pneumonia and association of its variation with antibiotic appropriateness.Prospective, observational cohort study.Two medical-surgical intensive care units at large urban hospitals affiliated with teaching institutions.Sixty-eight intubated patients with monomicrobial ventilator-associated pneumonia.None.QTA and serum C-reactive protein were measured in patients with suspected ventilator-associated pneumonia on diagnosis (baseline) and 96 hrs afterward (follow-up). Its logarithm value (logQTA) was calculated. LogQTA correlated positively with serum C-reactive protein (ρ = 0.46, p < .05), temperature (ρ = 0.20, p = .05), and white blood cell count (ρ = 0.22, p < .05). LogQTA decreased significantly more from baseline to follow-up in patients receiving appropriate empirical antibiotic therapy compared with those with inappropriate treatment (logQTA ratio 0.77 ± 0.22 vs. 1.02 ± 0.27, p < .05). Mean serum C-reactive protein levels showed a similar pattern, decreasing from baseline to follow-up in patients receiving appropriate empirical antibiotic treatment but not in episodes with inappropriate treatment (C-reactive protein ratio 0.58 ± 0.32 vs. 1.36 ± 1.11, p < .05). There was a positive correlation between serum C-reactive protein and logQTA variations (r2 = .59, p < .05). Adjusted mean serum C-reactive protein levels by analysis of covariance on follow-up were significantly lower in patients with appropriate antibiotic treatment than in those with inappropriate empirical treatment (103 ± 10 mg/L vs. 192 ± 14 mg/L, p < .05). A C-reactive protein ratio of 0.8 at 96 hrs was a useful indicator of appropriateness of antibiotic therapy (sensitivity 77%; specificity 87%; area under the receiver operating characteristic curve 0.86 [0.75–0.96]).C-reactive protein is a useful biochemical surrogate of bacterial burden in patients with ventilator-associated pneumonia. Follow-up measurements of serum C-reactive protein anticipate the appropriateness of antibiotic therapy.