Monte Carlo simulations; critically ill patients; epithelial lining fluid concentrations
Abstract :
[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
FRIPPIAT, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale
Musuamba, Flora Tshinanu
Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique
DENOOZ, Raphael ; Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
Charlier, Corinne ; Université de Liège - ULiège > Département de pharmacie > Chimie toxicologique
Van Bambeke, Francoise
Wallemacq, Pierre
DESCY, Julie ; Centre Hospitalier Universitaire de Liège - CHU > Microbiologie médicale
LAMBERMONT, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
LAYIOS, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
DAMAS, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.
Publication date :
12 September 2014
Journal title :
Journal of Antimicrobial Chemotherapy
ISSN :
0305-7453
eISSN :
1460-2091
Publisher :
Oxford University Press, London, United Kingdom
Volume :
70
Pages :
207-216
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 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.
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