Abstract:

In the present study, we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic (PK/PD) principles using Monte Carlo simulation (MCS). Based on PK/PD theory, MCS was performed using Crystal Ball software combining PK and PD parameters with 10 000 simulation runs to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for the seven clinically common dosing regimens of ceftriaxone (1 g qd, 1.5 g qd, 1 g bid, 2 g qd, 1 g tid, 1.5 g bid, and 2 g bid). A %fT ≥ 50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR ≥ 90% or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy, i.e. the clinically optimal regimen. All eight pathogenic bacteria had a CFR > 90% when the dosing regimen was 2 g bid and 1 g tid, seven pathogenic bacteria had a CFR > 90% when the dosing regimen was 1 g bid and 1.5 g bid, except for Pseudomonas aeruginosa, and all pathogenic bacteria had a CFR< 90% when the dosing regimen was 1 g qd and 1.5 g qd. The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections, and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.

Key words: Ceftriaxone, PK/PD, Monte Carlo simulation, Antibacterial drugs, Clinical efficacy