Affiliation:
1. Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut
Abstract
ABSTRACT
The OPTAMA Program is intended to examine typical antimicrobial regimens used in the treatment of common nosocomial pathogens and the likelihood of these regimens attaining appropriate pharmacodynamic exposure in different parts of the world. A 5,000-subject Monte Carlo simulation was used to estimate pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin-tazobactam, and ciprofloxacin against
Escherichia coli
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
, and
Pseudomonas aeruginosa
. Standard dosing regimens from North America were used. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and MIC data came from the 2002 MYSTIC Program. Ciprofloxacin displayed the lowest target attainment against all bacterial species (41 to 46% for
A. baumannii
, 53 to 59% for
P. aeruginosa
, and 80 to 85% for the
Enterobacteriaceae
). Increasing the dose to 400 mg every 8 h did not significantly increase target attainment against nonfermenters. Piperacillin-tazobactam target attainments were similar to that of ceftazidime against all pathogens. Higher doses of both compounds were needed to achieve better target attainments against
P. aeruginosa
. Overall, meropenem, imipenem, and cefepime attained the highest probabilities of attainment against the
Enterobacteriaceae
(99 to 100%). The carbapenems appear to be the most useful agents against
A. baumannii
(88 to 92%), and these agents, along with higher doses of any of the β-lactams, would be the most appropriate choices for empirical therapy for
P. aeruginosa
infection. Given the lack of agreement between percent susceptibility and probability of target attainment for certain antimicrobial regimens, a methodology employing stochastic pharmacodynamic analyses may be a more useful tool for differentiating the most-optimal compounds and dosing regimens in the clinical setting of initial empirical therapy.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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