TY - JOUR
T1 - Comparison of β-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics
AU - Burgess, David S.
AU - Frei, Christopher R.
N1 - Funding Information:
D.S.B. has received research grants, served as a consultant, or served on a speaker’s bureau for the following pharmaceutical companies: Merck & Co., Ortho-McNeil Pharmaceuticals, Roche Pharmaceuticals and Wyeth Pharmaceuticals. C.R.F. has received research grants from Merck & Co., Roche Pharmaceuticals, and Wyeth Laboratories.
Funding Information:
The authors would like to thank Michelle Tomasini and Michael Carden for their excellent technical assistance. This manuscript was presented in part at the 2004 Annual Meeting of the American College of Clinical Pharmacy, October 24–27, 2004 in Dallas, TX. This study was partially supported by an unrestricted grant from Merck & Co.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Bacterial
KW - Gram-negative aerobic bacteria
KW - Pharmacokinetics/pharmacodynamics
KW - Pneumonia
UR - http://www.scopus.com/inward/record.url?scp=27744468387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744468387&partnerID=8YFLogxK
U2 - 10.1093/jac/dki335
DO - 10.1093/jac/dki335
M3 - Article
C2 - 16162664
AN - SCOPUS:27744468387
VL - 56
SP - 893
EP - 898
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 5
ER -