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

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.

• Authors: Frédéric Frippiat, Flora Tshinanu Musuamba, Laurence Seidel, Adelin Albert, Raphaël Denooz, Corinne Charlier, Françoise Van Bambeke, Pierre Wallemacq, Julie Descy, Bernard Lambermont, Nathalie Layios, Pierre Damas, Michel Moutschen
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 70 Issue 1 Pg. 207-16 (Jan 2015) ISSN: 1460-2091 [Electronic] England
• PMID: 25216821 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Thienamycins
• Meropenem

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Critical Illness
• Cross Infection (drug therapy)
• Female
• Humans
• Infusions, Intravenous
• Male
• Meropenem
• Middle Aged
• Plasma (chemistry)
• Pneumonia, Bacterial (drug therapy)
• Prospective Studies
• Respiratory Mucosa (chemistry)
• Thienamycins (administration & dosage, pharmacokinetics)
• Young Adult