JAC Advance Access originally published online on September 14, 2005
Journal of Antimicrobial Chemotherapy 2005 56(5):893-898; doi:10.1093/jac/dki335
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Comparison of ß-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics
1 College of Pharmacy, The University of Texas at Austin, 1 University Station Stop A1900, Austin, TX, USA 78712; 2 Departments of Pharmacology and Medicine, The University of Texas Health Science Center at San Antonio, Clinical Pharmacy Programs-MSC 6220, 7703 Floyd Curl Dr., San Antonio, TX, USA 78229–3900; 3 Department of Pharmacology, The University of Texas Health Science Center at San Antonio, Clinical Pharmacy Programs-MSC 6220, 7703 Floyd Curl Dr., San Antonio, TX, USA 78229–3900
Received 27 May 2005; returned 5 July 2005; revised 19 August 2005; accepted 24 August 2005
* Corresponding author. Tel: +1-210-567-8329; Fax: +1-210-567-8328; Email: BurgessD{at}uthscsa.edu
Objectives: This study utilized pharmacokinetics/pharmacodynamics to compare ß-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 ß-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 ß-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
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