[Optimization of amoxicillin/clavulanate therapy based on pharmacokinetic/pharmacodynamic parameters in patients with...

Individualized optimization of amoxicillin/clavulanate (AMC) antimicrobial therapy in diabetic foot infection.

Pharmacokinetic analysis of individual steady-state plasma amoxicillin concentrations was done both in the i.v. infusion phase and in the oral phase of AMC, administered on the basis of the quantitative susceptibility of the detected microbe(s). The in vitro growth/killing dynamic parameters on model of Staphylococcus aureus as the most frequent isolate were evaluated. Therapeutic protocol optimization, leading to prediction of the earliest time to reduce the number of viable bacteria to 10-6 as a surrogate criterion of efficacy, was performed.

Based on individual plasma amoxicillin oscillations in 17 patients suffering from infected diabetic foot ulcers and the model microbial dynamic parameters, the reduction of the number of viable bacteria was reached significantly earlier after the administration of continuous i.v. AMC infusion than after the same daily AMC dose administered intermittently. In case of highly susceptible staphylococcal strain, highly frequent oral therapy of AMC (not longer than 8 hrs dosing interval) was also sufficiently effective. Decreasing plasma amoxicillin concentrations exponentially extended the time required for effective reduction of microbes.

Individualized optimization of amoxicillin/clavulanate dosage on the basis of growth/killing microbial dynamic parameters and antibiotic concentration/time fluctuations may enhance the antimicrobial effect and the treatment of infected non-critical ischemic diabetic foot ulcers.