Vol.53 No.5 May 2005
Clinical significance of pharmacokinetic/pharmacodinamic variables using Monte Carlo simulation in vancomycin treatment of pulmonary methicillin-resistant Staphylococcus aureus infection
1)Departments of Clinical Pathology and 2)Pharmacy, Tenri Hospital, 200 Mishima, Tenri, Nara, Japan
Abstract
In studying the relationship between pharmacokinetic variables for serum vancomycin (VCM) and therapeutic outcome, we analyzed data from 31 patients with pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). VCM was effective in 21. Comparing pharmacokinetic variables between the 21 responders and 10 nonresponders yielded the following median (interquartile range) within 1-2 hours after VCM administration was stopped: Cmax, 37.1 μg/mL (29.9-42) vs. 32.3 μg/mL (29.5-36.1) (P=0.32); trough, 10.5 μg/mL (8-12.4) vs. 8.7 μg/mL (6.7-11.2) (P=0.25); elimination constant (Ke), 0.17/h (0.10-0.22) vs. 0.15/hr (0.11-0.17) (P=0.67); and area-under-the-concentration curve (AUC), 410 μg · h/mL (349-455) vs. 318 μg/mL · hr (302-328) (P<0.01). AUC was the only statistically significant pharmacokinetic variable. Receiver operating characteristic curve analysis showed AUC cutoff of 330 μg/mL · hr (sensitivity, 76.2%; specificity, 80.0%). AUC distribution for the 21 responders and MIC distribution for VCM of 373 MRSA strains isolated at Tenri Hospital were integrated over 1,000 Monte Carlo simulation trials. The probability of attaining an AUC/MIC of ≥330 was 56.8%. These results indicate that AUC reflected VCM clinical efficacy for MRSA pneumonia, and the AUC cutoff was 330 μg/mL · hr. Monte Carlo simulation also indicated a low probability of attaining an AUC/MIC ratio ≥330. We therefore suggest that the AUC/MIC ratio be adopted as an index for VCM treatment.
Key word
MRSA, vancomycin, AUC/MIC, Monte Carlo simulation, pneumonia
Received
January 26, 2005
Accepted
March 16, 2005
Jpn. J. Chemother. 53 (5): 297-301, 2005
