Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.

Objectives: Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. Patients and methods: Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a >= 10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. Results: Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5x MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C-1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C-1/MIC >= 10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C-1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). Conclusions: In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C-1/MIC ratio than previously described might be necessary.