Pharmacodynamic evaluation of meropenem and cefotaxime for pediatric meningitis: a report from the OPTAMA program.
OBJECTIVE
To determine the probability of meropenem (Merrem, AstraZeneca Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.


METHODS
A 5,000-patient Monte Carlo simulation in a population of 10-year-old children with meningitis was conducted. Pediatric pharmacokinetic data were derived from the literature. Pathogen minimum inhibitory concentrations (MICs) were obtained from common bacteria that had caused meningitis collected during pediatric clinical trials. Time above the MIC exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or probability of target attainment was defined as 40% and 50% time above the MIC for meropenem and cefotaxime, respectively. High cumulative fractions of responses were defined as >90% probability of target attainment against the populations of bacteria.


RESULTS
Meropenem was calculated to achieve 94.7%, 94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H. influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S. pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and 84.8% cumulative fractions of response, respectively.


CONCLUSIONS
In a simulated population of 10-year-old children, meropenem had a high likelihood of attaining bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90% cumulative fraction of response against only N. meningitidis. Therefore, at the doses simulated, meropenem may be a more appropriate empiric choice for the treatment of bacterial meningitis in pediatric patients presumed to be caused by these pathogens until culture and susceptibility data are available.
Ellis
Jennifer M
JM
Department of Pharmacy Practice, University of Connecticut, School of Pharmacy, Storrs, USA.
Kuti
Joseph L
JL
Nicolau
David P
DP
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001835:Body Weight / Q000502:physiology; D002439:Cefotaxime / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008583:Meningitis, Haemophilus / Q000188:drug therapy / Q000382:microbiology; D008585:Meningitis, Meningococcal / Q000188:drug therapy / Q000382:microbiology; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000382:microbiology; D000077731:Meropenem; D009010:Monte Carlo Method; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D002439:Cefotaxime