Optimal treatment regimen of intravenous meropenem in critically ill patients

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“The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia” Frippiat et al (2015).

Reference:

Frippiat, F., Musuamba, F.T., Seide, L., Albert, A., Denooz, R., Charlier, C., Van Bambeke, F., Wallemacq, P., Descy, J., Lambermont, B., Layios, N., Damas, P. and Moutschen, M. (2015) Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study. Journal of Antimicrobial Chemotherapy. 70(1), p.207-216.

Abstract:

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.

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