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Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit‐isolated methicillin‐resistant Staphylococcus aureus
Author(s) -
Salem Ahmed Hamed,
Zhanel George G,
Ibrahim Safaa A,
Noreddin Ayman M
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12195
Subject(s) - daptomycin , dalbavancin , tigecycline , linezolid , vancomycin , medicine , pharmacodynamics , methicillin resistant staphylococcus aureus , pharmacology , staphylococcus aureus , pharmacokinetics , antibiotics , microbiology and biotechnology , biology , bacteria , genetics
Summary 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. 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 32 μg/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. Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g 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 (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively. 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 1 μg/mL.