Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Apr 2009
Randomized Controlled Trial Multicenter Study Comparative StudyUrinary bactericidal activity of Doripenem versus that of levofloxacin in patients with complicated urinary tract infections or pyelonephritis.
The aim of this study was to investigate the urinary bactericidal titers (UBTs) and 24-h area under the UBT-versus-time curve (AUBT) of intravenous doripenem (500 mg every 8 h [q8h]), a new carbapenem, versus those of intravenous levofloxacin (250 mg q24h) in patients with complicated urinary tract infections (cUTIs) or pyelonephritis. UBTs and AUBTs are pharmacokinetic/pharmacodynamic parameters able to reflect the activity of an antimicrobial substance in the urine. Doripenem and levofloxacin show comparable urinary excretion of approximately 80% and are therefore registered for the treatment of UTIs. ⋯ For levofloxacin, microbiological failures correlated well with low UBTs and AUBTs, whereas for doripenem there was no correlation. From this study, a calculated target attainment rate for levofloxacin predicting therapeutic success in patients with UTIs approximated mean UBTs of 100 over 24 h or AUBTs of 2,240. Doripenem demonstrated excellent urinary bactericidal activity with the dose administered and appears to be a good alternative in the empirical treatment of cUTI.
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Antimicrob. Agents Chemother. · Apr 2009
Randomized Controlled TrialPopulation pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia.
A population pharmacokinetic model of cefepime was constructed from data from adult critical care patients with ventilator-associated pneumonia (VAP). A total of 32 patients treated with high-dose cefepime, 2 g every 8 h (3-h infusion) or a renal function-adjusted equivalent dose, were randomized into two groups--26 for the initial model and 6 for model validation. Serum samples of cefepime were collected at steady state. ⋯ Time-concentration profiles were assessed for various dosing regimens, using 5,000-patient Monte Carlo simulations. Among the regimens, the likelihoods of 2 g every 8 h (3-h infusion) achieving free drug concentrations above the MIC for 50% of the dosing interval were 91.8%, 78.1%, and 50.3% for MICs of 8, 16, and 32 microg/ml, respectively. This study provides a pharmacokinetic model capable of predicting cefepime concentrations in critically ill patients with VAP.