Pharmacodynamic comparison of daptomycin and vancomycin against clinical isolates of methicillin-resistant Staphylococcus aureus in three European countries
Abstract number: P1987
Canut A., Rodríguez-Gascón A., Cercenado E., Betriú C., Labora A., Pedraz J.L.
Objective: A reduction in the efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) strains with high vancomycin MIC values (12 mg/L) has been described in recent studies. Accordingly, the objective of the current study was to calculate the probability of attaining targeted pharmacodynamic exposure for various regimens of vancomycin and daptomycin against clinical isolates of S. aureus collected in Belgium, United Kingdom and Spain.
Methods: Susceptibility data to vancomycin and daptomycin of clinical MRSA isolates from Belgium (n = 511), United Kingdom (n = 97) and Spain (n = 298) were analyzed. Steady-state exposure was assessed for the following antibiotic regimens: vancomycin (1000 mg/12 h, 1000 mg/8 h, 2000 mg/12 h, 1500 mg/8 h and 1500 mg/6 h) and daptomycin (4, 6, 8 mg/Kg every 24 h). Mean pharmacokinetic parameters and their distribution were extrapolated from published patients' studies for each antibiotic. The area under the concentration-time curve divided by the MIC (AUC/MIC) was utilised as the pharmacodynamic parameter to predict vancomycin and daptomycin efficacy (pharmacodynamic targets of >400 and >438, respectively). For vancomycin, Cmin,free/MIC was also calculated (values of >4). A 10000-patient Monte-Carlo simulation was performed to calculate the AUC/MIC for vancomycin and daptomycin and Cmin,free/MIC for vancomycin. Cumulative fraction of response (CFR) for the requisite pharmacodynamic target was calculated weighing the probability of target attainment at each MIC by the percentage of organism with that MIC.
Results: In Belgium, CFR higher than 90% was achieved with vancomycin doses higher than 1000 mg/8 h. However, in United Kingdom and in Spain, CFR > 90% is only achieved with the highest dose: 1500 mg/6 h. The differences are due to differences in susceptibility of the isolates; whereas in Belgium 100% of the isolates presented MIC values 1 mg/L, only 64% and 69% of the isolates reached these MIC values in United Kingdom and in Spain, respectively. Concerning daptomycin, CFR values higher than 90% are achieved with the lowest dose (4 mg/Kg) for isolates from Belgium, United Kingdom and Spain. CFR values of 100% were achieved with 6 mg/Kg and 8 mg/Kg in the isolates of the three countries.
Conclusion: Daptomycin had a greater likelihood of obtaining its requisite pharmacodynamic exposure against MARSA due to the excellent activity against all strains recovered in Belgium, United Kingdom and Spain.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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