Lepe José Antonio, García-Cabrera Emilio, Gil-Navarro María Victoria, Aznar Javier
Hospitales Universitarios Virgen del Rocío, Av Manuel Siurot s/n, 41013 Sevilla. Spain.
Rev Esp Quimioter. 2012 Jun;25(2):134-8.
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).
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.
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.
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.
本研究旨在基于蒙特卡洛模拟为鲍曼不动杆菌制定利福平的药代动力学-药效学（PK-PD）折点，并将其与法国微生物学会（SFM）确定的参考值进行比较。
对10000名受试者进行了静脉注射剂量为10mg/Kg/天和20mg/Kg/天的利福平蒙特卡洛模拟。使用鲍曼不动杆菌独特的临床分离株计算MIC的分布。计算的PK-PD参数为游离Cmax/MIC。
利福平分离株的MIC50和MIC90分别为2mg/L和32mg/L，范围在0.023 - 32mg/L之间。根据SFM制定的解释标准：468株（75.8%）分离株敏感（MIC≤4mg/L），150株（24.2%）不敏感（MIC>4mg/L）。对于10mg/Kg/天的剂量：在研究人群中通过蒙特卡洛模拟获得游离Cmax/MIC比值 = 8的概率（%）为0.4%，从最佳治疗（目标≥90%）获得的利福平MIC截止值为0.125mg/L。获得游离Cmax/MIC比值等于10的概率为0.2%，获得的MIC截止值<0.125mg/L。在20mg/kg/天的剂量下：获得游离Cmax/MIC比值等于8的概率为0.8%，获得的利福平MIC截止值为0.25mg/L。对于游离Cmax/MIC = 10，分别为0.6%和0.125mg/L。敏感分离株的百分比根据所用剂量和治疗目标在0%至1%之间。
从我们的PK/PD蒙特卡洛模拟获得的利福平折点与SFM确定的折点不同，尽管需要对患者进行进一步的临床研究来证实我们的发现并改善这种抗生素的使用。
