Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection

Abstract

The time that concentrations in serum are above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic parameter correlating with the therapeutic efficacy of beta-lactam antibiotics. The aim of this study was to demonstrate the T>MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection. The study was conducted with nine patients with ventilator-associated pneumonia. Each subject received meropenem in three regimens consecutively: (i) bolus injection of 1 g every 8 h for 24 h; (ii) 3-h infusion of 1 g every 8 h for 24 h; and (iii) 3-h infusion of 2 g every 8 h for 24 h. Following bolus injection, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 28.33% +/- 11.67%, 45.89% +/- 22.90%, 57.00% +/- 24.82%, and 74.67% +/- 17.94% of an 8-h interval, respectively. For the 3-h infusion of 1 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 37.78% +/- 20.57%, 58.11% +/- 24.38%, 72.67% +/- 21.97%, and 93.56% +/- 6.84% of an 8-h interval, respectively. For the 3-h infusion of 2 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 57.89% +/- 24.26%, 72.89% +/- 22.40%, 85.56% +/- 16.42%, and 98.56% +/- 3.28% of an 8-h interval, respectively. In conclusion, a 3-h infusion resulted in greater T>MICs than those after a bolus injection. For the treatment of infections caused by pathogens with intermediate resistance, a 3-h infusion of 2 g of meropenem every 8 h can provide concentrations in serum above the MIC of 16 microg/ml for almost 60% of an 8-h interval.

FIG. 1.

Mean serum meropenem concentration-time data for nine patients with VAP following administration of 1 g by bolus injection (filled squares), 1 g by a 3-h infusion (open circles), and 2 g by a 3-h infusion (filled triangles).