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, Christopher R. Frei

    Research output: Contribution to journalArticlepeer-review

    31 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)893-898
    Number of pages6
    JournalJournal of Antimicrobial Chemotherapy
    Volume56
    Issue number5
    DOIs
    StatePublished - Nov 2005

    Keywords

    • Bacterial
    • Gram-negative aerobic bacteria
    • Pharmacokinetics/pharmacodynamics
    • Pneumonia

    ASJC Scopus subject areas

    • Pharmacology
    • Microbiology (medical)
    • Infectious Diseases
    • Pharmacology (medical)

    Fingerprint

    Dive into the research topics of 'Comparison of β-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics'. Together they form a unique fingerprint.

    Cite this