Journal Article

Comparison of β-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics

David S. Burgess and Christopher R. Frei

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 5, pages 893-898
Published in print November 2005 | ISSN: 0305-7453
Published online September 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki335
Comparison of β-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics

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Objectives: This study utilized pharmacokinetics/pharmacodynamics to compare β-lactam regimens for the empirical and definitive treatment of Gram-negative pulmonary infections in the ICU.

Methods: Susceptibility data were extracted from the 2002 Intensive Care Unit Surveillance System (ISS) and pharmacokinetic parameters were obtained from published human studies. Monte Carlo simulation was used to model the free percent time above the MIC (free %T > MIC) for 18 β-lactam regimens against all Gram-negative isolates, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. The cumulative fraction of response (CFR) was determined for bacteriostatic and bactericidal targets (free %T > MIC): penicillins (≥30/50%), cephalosporins/monobactams (≥40/70%) and carbapenems (≥20/40%).

Results: The 2002 ISS database contained MICs for 2408 Gram-negative isolates including 1430 Enterobacteriaceae, 799 P. aeruginosa, and 179 A. baumannii. Imipenem had the highest percentage susceptible for all Gram-negatives, Enterobacteriaceae and A. baumannii, while piperacillin/tazobactam had the highest percentage susceptible for P. aeruginosa. For empirical therapy, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h demonstrated the highest CFR. For definitive therapy, imipenem 0.5 g every 6 h, ertapenem 1 g daily and cefepime 2 g every 8 h, cefepime 1 g every 8 h and cefepime 1 g every 12 h had the highest bactericidal CFR against Enterobacteriaceae; ceftazidime 2 g every 8 h, cefepime 2 g every 8 h, piperacillin/tazobactam 3.375 g every 4 h, ceftazidime 1 g every 8 h and aztreonam 1 g every 8 h against P. aeruginosa; and imipenem 0.5 g every 6 h, ticarcillin/clavulanate 3.1 g every 4 h, ceftazidime 2 g every 8 h, cefepime 2 g every 8 h and ticarcillin/clavulanate 3.1 g every 6 h against A. baumannii.

Conclusions: Based on pharmacokinetics/pharmacodynamics, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h should be the preferred β-lactam regimens for the empirical treatment of Gram-negative pulmonary infections in the ICU. The order of preference varied against Enterobacteriaceae, P. aeruginosa and A. baumannii.

Keywords: Pharmacokinetics/pharmacodynamics; Gram-negative aerobic bacteria; pneumonia; bacterial

Journal Article.  4098 words. 

Subjects: Medical Oncology ; Critical Care

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