Abstract:
OBJECTIVE To evaluate the dosing regimens of daptomycin for treatment of Staphylococcus and
Enterococcus faecalis infections by Monte Carlo simulation (MCS) based on pharmacokinetic/pharmacodynamic (PK/PD) parameters of daptomycin so as to provide reference for reasonable clinical use of daptomycin.
METHODS The data regarding bacterial resistance surveillance were collected from Shandong Provincial Hospital Affiliated to Shandong First Medical University, and the minimum inhibitory concentrations (MIC) of daptomycin against pathogenic bacteria were determined by broth dilution method. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of 7 dosing regimens were predicated through MCS; the dosing regimens were 4 mg/(kg·d), 5 mg/(kg·d), 6 mg/(kg·d), 500 mg/d, 7 mg/(kg·d), 8 mg/(kg·d) and 9 mg/(kg·d), respectively.
RESULTS The CFRs of all the 7 dosing regimens were greater than 90% for
Staphylococcus aureus infection, indicating that all of the dosing regimens could acquired satisfied effect during the process of empirical therapy. The dosage needed to be 8 mg/(kg·d) or more for
Enterococcus faecalis infection, then its CFR could be greater than 90%. Although the PTA of
Staphylococcus epidermidis infection was as same as that of the
S. aureus infection, the dosing regimen with no less than 8 mg/(kg·d) could make the CFR greater than 90% due to the different distributions of MIC.
CONCLUSION The dosing regimens of daptomycin for treatment of the gram-positive bacteria infection need to be adjusted individually based on the species of pathogens and MICs, the empirical therapeutic regimen should be formulated based on the epidemiological data so as to optimize the anti-infection effect and postpone the drug resistance.