Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit-isolated methicillin-resistant Staphylococcus aureus

1. The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin-resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings. 2. Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32g/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study. 3. Analysis of the simulation results suggested the breakpoints of 4g/mL for ceftobiprole (500mg/2h t.i.d.), 0.25g/mL for dalbavancin (1000mg), 0.12g/mL for daptomycin (4mg/kg q.d. and 6mg/kg q.d.) and tigecycline (50mg b.i.d.), and 2g/mL for linezolid (600mg b.i.d.) and vancomycin (1g b.i.d. and 1.5g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4mg/kg/day), daptomycin (6mg/kg/day), linezolid, tigecycline, vancomycin (1g b.i.d.) and vancomycin (1.5g b.i.d.), respectively. 4. In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin-resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1g/mL.