Rifampin breakpoint for Acinetobacter baumannii based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation.
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.


CONCLUSIONS
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.
Hospitales Universitarios Virgen del Rocío, Av Manuel Siurot s/n, 41013 Sevilla. Spain. jalepe@cica.es
José Antonio
JA
Lepe
Emilio
E
García-Cabrera
María Victoria
MV
Gil-Navarro
Javier
J
Aznar
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005602:France; D006801:Humans; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011336:Probability; D012016:Reference Values; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D012293:Rifampin