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  • Title: Rifampin breakpoint for Acinetobacter baumannii based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation.
    Author: Lepe JA, García-Cabrera E, Gil-Navarro MV, Aznar J.
    Journal: Rev Esp Quimioter; 2012 Jun; 25(2):134-8. PubMed ID: 22707102.
    Abstract:
    OBJECTIVE: The aim of this study is to develop a pharmacokinetic-pharmacodynamic (PK-PD) rifampin breakpoint for Acinetobacter baumannii based on Monte Carlo simulation and to compare it with the reference value establish by the French Society for Microbiology (SFM). METHODS: A 10,000 subject's Monte Carlo simulation for rifampin with intravenous dose of 10 mg/Kg/day and 20 mg/Kg/day was performed. The distribution of MIC was calculated using unique clinical isolates of A. baumannii. The PK-PD parameter calculated was Cmax free/MIC. RESULTS: The isolates rifampin MIC50 and MIC90 were 2 and 32 mg/L respectively, ranging between 0.023-32 mg/L. According to interpretive criteria established by the SFM: 468 (75.8%) isolates were susceptible (MIC ≤ 4 mg/L) and 150 (24.2%) were non susceptible (MIC > 4 mg/L). For 10 mg/Kg/day dose: the probability (%) of attaining Cmax free/MIC ratio values = 8 by Monte Carlo simulation in the study population was 0.4%, the rifampin MIC cut off value obtained from an optimal treatment (target ≥ 90%), was 0.125 mg/L. The probability of obtaining a Cmax free/MIC ratio equal to 10 was 0.2% and the MIC cut off value obtained <0.125 mg/L. At doses of 20 mg/kg/day: the probability of obtaining a Cmax free/MIC ratio equal to 8 was 0.8%, the rifampin MIC cut off value obtained was 0.25 mg/L. For a Cmax free/MIC = 10, it was 0.6% and 0.125 mg/L, respectively. The percentage of susceptible isolates ranging 0% to 1%, depending on the dose and therapeutic target used. CONCLUSION: the rifampin breakpoints obtained from our PK/PD Monte Carlo simulation differ from those established by SFM, although further clinical studies in patients are needed to confirm our findings and improve the use of this antibiotic.
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