[Application of the MIC breakpoints based on pharmacokinetics and pharmacodynamics parameter in the clinical...

The effectiveness of time-dependent antibiotics such as beta-lactams is related to the time above the MIC (TAM, %). We constructed a program to calculate the TAMs of beta-lactams using the pharmacokinetic parameters of the Japanese dosing regimen of a phase I study of the Japanese Society for Antimicrobial Chemotherapy (JSAC), and compared them with the MIC breakpoints published by the National Committee for Clinical Laboratory Standards (NCCLS) and JSAC. If the effective TAM was assumed to be more than 40% of the dosing interval, the pharmacokinetic/pharmacodynamic (PK/PD) breakpoints calculated by our program were in agreement with the JSAC breakpoints for pneumonia within 1 dilution MIC. When comparing with the NCCLS breakpoints for Enterobacteriaceae or Staphylococcus, the PK/PD breakpoints dosing three times per day of ampicillin (1 g, intravenous dose; i.v.), piperacillin (2 g, i.v.), cefotaxime (1 g, i.v.) and cefmetazole (1 g, i.v.) were calculated to be less than 2-fold dilution MIC, and those of amoxicillin (0.25 g, oral dose; p.o.) and cefaclor (0.5 g, p.o.) were calculated to be less than 3- to 4-fold dilution of MIC. Our program could calculate TAMs and PK/PD breakpoints by inputting the two factors of MIC and dosing interval. If this information is routinely reported to physicians from clinical laboratories, an appropriate dosing schedule could be proposed for various infectious cases.