1. J Antimicrob Chemother. 2014 Sep 12. pii: dku354. [Epub ahead of print]

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

Frippiat F(1), Musuamba FT(2), Seidel L(3), Albert A(3), Denooz R(4), Charlier
C(4), Van Bambeke F(5), Wallemacq P(6), Descy J(7), Lambermont B(8), Layios N(8),
Damas P(8), Moutschen M(9).

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.

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.

© 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: journals.permissions@oup.com.

PMID: 25216821  [PubMed - as supplied by publisher]