Monte Carlo simulation study to optimize administration regimens of linezolid, teicoplanin and daptomycin for Staphylococcal bloodstream infections / 中华传染病杂志

ABSTRACT

Objective:To predict and evaluate the antibacterial efficacy of linezolid, teicoplanin and daptomycin against Staphylococci bloodstream infections with Monte Carlo simulation, and to optimize the clinical administration program. Methods:A total of 1 847 Staphylococci strains isolated from blood samples between January 2018 to December 2019 were collected with the help of the Blood Bacterial Resistant Investigation Collaborative System (BRICS). Minimum inhibitory concentrations (MIC) of linezolid and daptomycin were detected by broth dilution method, while MIC of teicoplanin were detected by agar dilution method. The dosage regimens of linezolid were 800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours. The dosage regimens of teicoplanin were 400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours, and 1 000 mg once every 12 hours. The dosage regimens of daptomycin were 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1and 12 mg·kg -1·d -1. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of three different dosage regimens were calculated by Monte Carlo simulation. A dosage regimen with CFR≥90.0% was a reasonable choice for empirical antimicrobial therapy. Results:PTA of linezolid against Staphylococci when MIC≤0.500 mg/L at four dosage regimens (800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours) were all over 90.0%. When MIC was 1.000 mg/L, the PTA of linezolid against Staphylococci under the dosages of 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours were 92.2%, 96.6% and 97.6%, respectively. The CFR of the four dosage regimens of linezolid were 73.9%, 83.7%, 90.8% and 95.3%, respectively. When MIC≤1.000 mg/L, PTA of teicoplanin against Staphylococci were all 100.0% at four dosage regimens (400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours and 1 000 mg once every 12 hours). When MIC was 2.000 mg/L, the PTA of teicoplanin (800 mg once every 12 hours and 1 000 mg once every 12 hours) against Staphylococci were both 100.0%. The CFR of the four dosage regimens of teicoplanin were 90.8%, 92.8%, 93.5% and 94.6%, respectively. When MIC≤0.500 mg/L, PTA of daptomycin against Staphylococci under the five dosages of 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1 were all over 90.0%. When MIC was 1.000 mg/L, the PTA of daptomycin against Staphylococci under the three dosages of 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1were 96.9%, 100.0% and 100.0%, respectively. The CFR of the five dosage regimens of daptomycin against Staphylococci were 97.4%, 99.2%, 99.9%, 100.0% and 100.0%, respectively. Conclusions:Linezolid (600 mg once every 12 hours), teicoplanin (400 mg once every 12 hours) and daptomycin (4 mg·kg -1·d -1) can achieve satisfactory antibacterial activity for Staphylococci bloodstream infections.