Achieving adequate antibiotic exposure in peripheral tissue remains an important challenge in the management of infected diabetic foot ulcers (iDFUs), particularly for time-dependent antibiotics. A randomized study published in Diabetes/Metabolism Research and Reviews evaluated serum and tissue availability of ceftazidime and amoxicillin/clavulanate administered by bolus dosing or continuous infusion in patients with iDFUs.

Sixty patients were randomized to 4 treatment groups: ceftazidime bolus, ceftazidime continuous infusion, amoxicillin/clavulanate bolus, and amoxicillin/clavulanate continuous infusion. Antibiotic concentrations in tissue adjacent to the ulcer were measured using microdialysis after steady-state concentrations were achieved. Pharmacodynamic activity was assessed using peak concentrations, area under the curve, and the proportion of time free drug concentrations remained above the minimum inhibitory concentration (fT > MIC).

Findings

• All patients achieved serum fT > MIC targets for ceftazidime, while target attainment for amoxicillin/clavulanate occurred in 100% of bolus-treated patients and 89% of patients receiving continuous infusion.
• Tissue target attainment was lower overall, occurring in 60% of patients receiving ceftazidime bolus, 73% receiving ceftazidime continuous infusion, 79% receiving amoxicillin/clavulanate bolus, and 83% receiving amoxicillin/clavulanate continuous infusion.
• Bolus administration produced rapid serum peak concentrations within 5 minutes, followed by delayed tissue peak concentrations at 30 to 60 minutes and subsequent decline.
• Continuous infusion produced gradual increases in antibiotic concentrations over time.

Serum pharmacodynamic targets for ceftazidime and amoxicillin/clavulanate were achieved consistently in patients with iDFUs, although tissue target attainment remained substantially lower. Continuous infusion showed numerically higher tissue exposure than bolus administration, supporting the importance of considering peripheral tissue pharmacokinetics during antibiotic treatment of iDFUs.