2023 年 49 巻 1 号 p. 1-11
The development of individualized dosing methods based on pharmacokinetics/pharmacodynamics (PK/PD) for PK of antimicrobials and their effects at the site of infection is essential for developing precise prevention and treatment strategies for infectious diseases. We conducted translational and clinical research to establish an individualized optimal dosing method of antimicrobials for the prevention and treatment of infectious diseases based on PK/PD analysis. This review summarizes the evaluation of the PK/PD analysis.
1) During cardiovascular surgery, ampicillin/sulbactam (ABPC/SBT) was administered at a dose of 1.5 g every 4 h at a creatinine clearance (CLcr) of 60 and 90 mL/min, and at an interval of 6 h in patients with cardiopulmonary bypass. In dialysis patients, there is no need for re-administration during prolonged surgery (12 h).
2) SBT, a β-lactamase inhibitor, was effective against Acinetobacter baumannii. The mouse thigh infection model showed the best PK/PD index when the free drug concentration remained above the minimum inhibitory concentration (fT > MIC) (R2 = 0.987). SBT showed maximum bactericidal activity against A. baumannii when fT > MIC of ≥60％. PK/PD simulations showed that 1 g every 6 h at a CLcr of 60 mL/min was sufficient against A. baumannii.
3) The evaluation of the dosing regimen of meropenem in hemodiafiltration patients using a drug elimination model showed that a dose of 0.25 g once daily for MIC ≤ 8 µg/mL (usual treatment of infection) and a dose of 0.5 g once daily for MIC = 16 µg/mL (severe infection) were effective.
