Comparison of the pharmacodynamics of imipenem in patients with ventilator-associated pneumonia following administration by 2 or 0.5 h infusion

The aim of this study was to compare the t > MICs of imipenem between administration by a 2 h infusion with a 0.5 h infusion. The study was a randomized three-way crossover in nine patients with ventilator-associated pneumonia. Each subject received imipenem in three regimens consecutively: (i) a 0.5 h infusion of 0.5 g every 6 h for 24 h; (ii) a 2 h infusion of 0.5 g every 6 h for 24 h; and (iii) a 2 h infusion of 1 g every 6 h for 24 h. Following the 0.5 h infusion of 0.5 g of imipenem, the percentages of the t > 4 x MICs of 4, 2 and 1 mg/L were 20.32 +/- 9.32%, 44.11 +/- 16.40% and 64.67 +/- 20.56% of a 6 h interval, respectively. For the 2 h infusion of 0.5 g of imipenem, the percentages of the t > 4 x MICs of 4, 2 and 1 mg/L were 17.71 +/- 19.27%, 53.75 +/- 19.30% and 76.54 +/- 17.36% of a 6 h interval, respectively. For the 2 h infusion of 1 g of imipenem, the percentages of the t > 4 x MICs of 4, 2 and 1 mg/L were 60.26 +/- 23.96%, 77.78 +/- 20.11% and 93.35 +/- 8.26% of a 6 h interval, respectively. The 2 h infusions of imipenem resulted in greater t > MICs than the 0.5 h infusion. For infections caused by pathogens with high MICs, a 2 h infusion of 1 g of imipenem every 6 h can provide plasma concentrations above the MIC of 4 mg/L for 60% of a 6 h interval.