| Autor: |
Bulik, Catharine C., Christensen, Henry, Li, Peng, Sutherland, Christina A., Nicolau, David P., Kuti, Joseph L. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; February 2010, Vol. 54 Issue: 2 p804-810, 7p |
| Abstrakt: |
ABSTRACTWe have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosawith MICs of ≤16 μg/ml. The objective of this experiment was to compare the efficacy of this high-dose, prolonged-infusion regimen against carbapenemase-producing Klebsiella pneumoniaeisolates with the efficacy against P. aeruginosaisolates having similar meropenem MICs. An in vitropharmacodynamic model was used to simulate human serum concentrations. Eleven genotypically confirmed K. pneumoniaecarbapenemase (KPC)-producing isolates and six clinical P. aeruginosaisolates were tested for 24 h, and time-kill curves were constructed. High-performance liquid chromatography (HPLC) was used to verify meropenem concentrations in each experiment. Meropenem achieved a rapid ≥3 log CFU reduction against all KPC isolates within 6 h, followed by regrowth in all but two isolates. The targeted %fT>MIC (percent time that free drug concentrations remain above the MIC) exposure was achieved against both of these KPC isolates (100% fT>MIC versus MIC = 2 μg/ml, 75% fT>MIC versus MIC = 8 μg/ml). Against KPC isolates with MICs of 8 and 16 μg/ml that did regrow, actual meropenem exposures were significantly lower than targeted due to rapid in vitrohydrolysis, whereby targeted %fT>MIC was reduced with each subsequent dosing. In contrast, a ≥3 log CFU reduction was maintained over 24 h for all Pseudomonasisolates with meropenem MICs of 8 and 16 μg/ml. Although KPC and P. aeruginosaisolates may share similar meropenem MICs, the differing resistance mechanisms produce discordant responses to a high-dose, prolonged infusion of meropenem. Thus, predicting the efficacy of an antimicrobial regimen based on MIC may not be a valid assumption for KPC-producing organisms. |
| Databáze: |
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