Efficacy of Standard Meropenem Dosing in Healthcare-Associated Meningitis: Is It Universal?
Abstract
Central nervous system (CNS) infections related to external ventricular drains (EVD) represent a frequent and serious complication of invasive CNS procedures, particularly those due to Gram-negative bacilli (GNB). Meropenem is one of the first-line treatments recommended whereas its limited CSF diffusion, with few studies with proven CNS infections. The multicenter PK/PD study evaluated the impact of EVD-related infections on meropenem distribution in cerebrospinal fluid (CSF) in 28 neuro-ICU patients with EVD, receiving meropenem via intermittent or continuous infusions (6-8 g/day), by comparing patients with confirmed CNS infection (n = 14) to those with extra-CNS infection (n = 14). Theoretical efficacy of different dosing strategies was assessed by Monte Carlo simulations. Probability of target attainment (PTA) and cumulative fractions of response (CFRs) were derived as the percentage of individuals achieving at steady-state 100% T > MIC for each dosing regimen using meropenem MIC frequency distributions for P. aeruginosa, K. pneumoniae, E. cloacae, and S. marcescens. A limited penetration of meropenem into CSF was observed, with a CSF/plasma AUC ratio of 16.3 ± 11.4% in CNS infections compared to 6.0 ± 4.5% in extra-CNS infections, highlighting the significant impact of infection. In patients with CNS infection, PTA in CSF was> 90% for MIC up to 0.25 mg/L with 6 g/d and reached 89.7% with 8 g/d for MIC of 1 mg/L. Overall, a daily dose of 6 g appears sufficient to treat CNS infections caused by E. cloacae, K. pneumoniae, and S. marcescens, whereas none of the dosing regimens tested seem adequate for P. aeruginosa, which more frequently exhibits high MICs > 1 mg/L.
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BibTeX
@article{chauzy2026efficacy,
title = {{Efficacy of Standard Meropenem Dosing in Healthcare-Associated Meningitis: Is It Universal?}},
author = {Alexia Chauzy and Carine Dominique and Hugues de Courson and Thu Huyen Doan and Russel Chabanne and Kévin Chalard and Gilles Francony and Sigismond Lasocki and Karim Lakhal and Pierre-Etienne Leblanc and Michel Wolff and Charles Grégoire and Frédéric Dailler and Fanny Bernard and Corinne Lorrain and Christophe Adier and Sandrine Marchand and Nicolas Grégoire and Claire Dahyot-Fizelier},
journal = {Anaesthesia Critical Care \& Pain Medicine},
year = {2026},
month = oct,
doi = {10.1016/j.accpm.2026.101936},
url = {https://hal.science/hal-05836478v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy of Standard Meropenem Dosing in Healthcare-Associated Meningitis: Is It Universal?
AU - Alexia Chauzy
AU - Carine Dominique
AU - Hugues de Courson
AU - Thu Huyen Doan
AU - Russel Chabanne
AU - Kévin Chalard
AU - Gilles Francony
AU - Sigismond Lasocki
AU - Karim Lakhal
AU - Pierre-Etienne Leblanc
AU - Michel Wolff
AU - Charles Grégoire
AU - Frédéric Dailler
AU - Fanny Bernard
AU - Corinne Lorrain
AU - Christophe Adier
AU - Sandrine Marchand
AU - Nicolas Grégoire
AU - Claire Dahyot-Fizelier
PY - 2026
DA - 2026/10/23
JO - Anaesthesia Critical Care & Pain Medicine
DO - 10.1016/j.accpm.2026.101936
UR - https://hal.science/hal-05836478v1
AB - Central nervous system (CNS) infections related to external ventricular drains (EVD) represent a frequent and serious complication of invasive CNS procedures, particularly those due to Gram-negative bacilli (GNB). Meropenem is one of the first-line treatments recommended whereas its limited CSF diffusion, with few studies with proven CNS infections. The multicenter PK/PD study evaluated the impact of EVD-related infections on meropenem distribution in cerebrospinal fluid (CSF) in 28 neuro-ICU patients with EVD, receiving meropenem via intermittent or continuous infusions (6-8 g/day), by comparing patients with confirmed CNS infection (n = 14) to those with extra-CNS infection (n = 14). Theoretical efficacy of different dosing strategies was assessed by Monte Carlo simulations. Probability of target attainment (PTA) and cumulative fractions of response (CFRs) were derived as the percentage of individuals achieving at steady-state 100% T > MIC for each dosing regimen using meropenem MIC frequency distributions for P. aeruginosa, K. pneumoniae, E. cloacae, and S. marcescens. A limited penetration of meropenem into CSF was observed, with a CSF/plasma AUC ratio of 16.3 ± 11.4% in CNS infections compared to 6.0 ± 4.5% in extra-CNS infections, highlighting the significant impact of infection. In patients with CNS infection, PTA in CSF was> 90% for MIC up to 0.25 mg/L with 6 g/d and reached 89.7% with 8 g/d for MIC of 1 mg/L. Overall, a daily dose of 6 g appears sufficient to treat CNS infections caused by E. cloacae, K. pneumoniae, and S. marcescens, whereas none of the dosing regimens tested seem adequate for P. aeruginosa, which more frequently exhibits high MICs > 1 mg/L.
SN - 2352-5568
ER -