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 ≥103 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 5× MIC for imipenem were 100% (8–100) and 74% (3–100), respectively. The median C1/MIC ratio for amikacin was 23 (1–76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/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 C1/MIC ratio than previously described might be necessary.