Penetration of meropenem into epithelial lining fluid of patients with ventilator-associated pneumonia.
Antimicrob Agents Chemother
; 55(4): 1606-10, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21300830
ABSTRACT
Antibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia (VAP). Surprisingly few studies have quantified the penetration of ß-lactam agents into the lung, as measured by the ratio of area under the concentration-time curve (AUC) in epithelial lining fluid (ELF) to AUC in plasma (AUC(ELF)/AUC(plasma) ratio). These have typically involved noninfected patients. This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP. Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer (big nonparametric adaptive grid [BigNPAG]). A Monte Carlo simulation was performed to estimate the range of ELF/plasma penetration ratios one would expect to observe in patients with VAP, as measured by the AUC(ELF)/AUC(plasma) ratio. The range of AUC(ELF)/AUC(plasma) penetration ratios predicted by the Monte Carlo simulation was large. The 10th percentile of lung penetration was 3.7%, while the 90th percentile of penetration was 178%. The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria like Pseudomonas aeruginosa, then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Líquidos Corporales
/
Tienamicinas
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Neumonía Asociada al Ventilador
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Antibacterianos
Tipo de estudio:
Clinical_trials
/
Health_economic_evaluation
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA