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- Title
Rifampin breakpoint for Acinetobacter baumannii based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation.
- Authors
Lepe, José Antonio; García-Cabrera, Emilio; Gil-Navarro, María Victoria; Aznar, Javier
- 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 Micro-biology (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 Cmaxfree/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 Cmaxfree/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 Cmaxfree/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 Cmaxfree/MIC ratio equal to 8 was 0.8%, the rifampin MIC cut off value obtained was 0.25 mg/L. For a Cmaxfree/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.
- Subjects
RIFAMPIN; ACINETOBACTER baumannii; PHARMACOKINETICS; PHARMACODYNAMICS; MONTE Carlo method; MICROBIAL sensitivity tests; ANTIBIOTICS
- Publication
Revista Española de Quimioterapia, 2012, Vol 25, Issue 2, p134
- ISSN
0214-3429
- Publication type
Article