{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T00:07:33Z","timestamp":1794269253309,"version":"4.9.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Aims\/hypothesis<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>potential<\/jats:italic> efficacy was <jats:italic>assessed by evaluating<\/jats:italic> the maximum serum and tissue ATB concentrations(C<jats:sub>max<\/jats:sub> and C<jats:sub>max-tissue<\/jats:sub>)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(\u2265100% <jats:sub>tissue<\/jats:sub> and \u226550%\/60% <jats:sub>tissue<\/jats:sub> fT&amp;gt;MIC). Vascular status was assessed by triplex ultrasound, ankle\u2013brachial and toe\u2013brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO<jats:sub>2<\/jats:sub>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following bolus administration, the C<jats:sub>max<\/jats:sub> of AMC was 91.8 \u00b1 52.5 \u03bcgmL<jats:sup>-1<\/jats:sup> and the C<jats:sub>max-tissue<\/jats:sub> of AMC was 7.25 \u00b1 4.5 \u03bcgmL<jats:sup>-1<\/jats:sup>(<jats:italic>P<\/jats:italic>&amp;lt;0.001). The C<jats:sub>max<\/jats:sub> for CTZ was 186.8 \u00b1 44.1 \u03bcgmL<jats:sup>-1<\/jats:sup> and the C<jats:sub>max-tissue<\/jats:sub> of CTZ was 18.6 \u00b1 7.4 \u03bcgmL<jats:sup>-1<\/jats:sup>(<jats:italic>P<\/jats:italic>&amp;lt;0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT&amp;gt;MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both C<jats:sub>max-tissue<\/jats:sub> and AUC<jats:sub>tissue<\/jats:sub> and arterial flow. Specifically, the correlation coefficient for the first phase was <jats:italic>r=<\/jats:italic>0.42; (<jats:italic>P<\/jats:italic>=0.045), and for the second phase, it was <jats:italic>r<\/jats:italic>=0.55(<jats:italic>P<\/jats:italic>=0.01)and <jats:italic>r<\/jats:italic>=0.5(<jats:italic>P<\/jats:italic>=0.021).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1326179","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T04:28:09Z","timestamp":1715056089000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? 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