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J Antimicrob Chemother. 2015 Jan;70(1):207-16. doi: 10.1093/jac/dku354. Epub 2014 Sep 12.

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

Author information

1
Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium f.frippiat@chu.ulg.ac.be.
2
School of Pharmacy, University College, London, UK.
3
Department of Biostatistics, University Hospital of Liège, Liège, Belgium.
4
Department of Toxicology, University Hospital of Liège, Liège, Belgium.
5
Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
6
Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium.
7
Department of Microbiology, University Hospital of Liège, Liège, Belgium.
8
Intensive Care Unit, University Hospital of Liège, Liège, Belgium.
9
Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium.

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.

KEYWORDS:

Monte Carlo simulations; critically ill patients; epithelial lining fluid concentrations

PMID:
25216821
DOI:
10.1093/jac/dku354
[Indexed for MEDLINE]

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