Daptomycin Rationale for the EUCAST clinical breakpoints, version ...

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Daptomycin - EUCAST Rationale document (http://www.eucast.org) 6 (10)6. Monte Carlo simulations and Pk/Pd breakpointsThere is considerable variation in the pharmacodynamic target AUC/MIC required for antibacterial effect in different studies. The pharmacodynamic targetis taken from what is considered the best published data (reference 2, section 5). The total drug AUC/MIC required for a bacteriostatic effect against S.aureus is 438 ± 67 (range 120-537). If a 2 log drop is chosen, the target increases to 1061 ± 296. This higher target may be more appropriate for patientiv therapy, hence again the target selected is favourable to the drug.Monte Carlo simulation was performed using a virtual AUC distribution based on the mean, SD, maximum and minimum values as published (section 4).A normal Gaussian distribution is assumed. These conditions are used as we do not have the actual AUC distributions for either volunteers or patients.Using a mean target AUC/MIC of 438, the probability of target attainment just misses a proposed target attainment of >80% for MICs of < 1mg/L, evenusing favourable Pk data and a bacteriostatic AUC/MIC target (Table 1). A probability of target attainment of 100% is obtained for MICs of
Daptomycin - EUCAST Rationale document (http://www.eucast.org) 7 (10)Figure 1: Daptomycin MIC distribution and probability of target attainment for S. aureusProbability of target attainment withAUC/MIC target of 358 for staphylococci10080PTA604020Target AUC/MIC = 35800.125 0.25 0.5 1 2 4 8MIC mg/L
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Daptomycin Rationale for the EUCAST clinical breakpoints, version ...

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