Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.

Aims/hypothesis: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status.

Methods: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB efficacy was the maximum serum and tissue ATB concentrations(C and C)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% and ≥50%/60% fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO).

Results: Following bolus administration, the C of AMC was 91.8 ± 52.5 μgmL and the C of AMC was 7.25 ± 4.5 μgmL(<0.001). The C for CTZ was 186.8 ± 44.1 μgmL and the C of CTZ was 18.6 ± 7.4 μgmL(<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both C and AUC and arterial flow. Specifically, the correlation coefficient for the first phase was 0.42; (=0.045), and for the second phase, it was =0.55(=0.01)and =0.5(=0.021).

Conclusions: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.