Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: The PROMESSE study

Objectives: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. Patients and methods: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T>1-fold and 4-fold MIC), for 1 or 2 g administered by either method. Results: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean±SEM: 0.29±0.030 versus 0.20±0.033, P=0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T>1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T>4-fold MIC in plasma. Conclusions: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.