{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:33:06Z","timestamp":1760059986760,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: With increasing pharmacokinetic evidence suggesting the inadequacy of conventional dose intravenous co-amoxiclav (IVCA) 1.2 g Q8H in targeting Enterobacterales, our institution antibiotic guidelines optimised dosing recommendations for diabetic foot infection (DFI) management to 1.2 g Q6H in August 2023. In this study, we aim to evaluate the efficacy and safety of the optimised dose IVCA in DFI treatment. Methods: In this single-centre cohort study, patients \u2265 21 years with DFI, creatinine clearance \u2265 50 mL\/min, and weight &gt; 50 kg, who were prescribed IVCA 1.2 g Q8H (standard group (SG)), were compared with those prescribed IVCA 1.2 g Q6H (optimised group (OG)). Patients who were pregnant, immunocompromised, had nosocomial exposure in last 3 months, or received &lt; 72 h of IVCA were excluded. The primary efficacy outcome was clinical deterioration at end of IVCA monotherapy. The secondary efficacy outcomes include 30-day readmission and mortality, empiric escalation of antibiotics, lower limb amputation, and length of hospitalisation. The safety outcomes include hepatotoxicity, renal toxicity, and diarrhoea. Results: There were 189 patients (94 in SG; 95 in OG) included. Patients in SG (31.9%) were twice as likely to experience clinical deterioration compared to OG (16.8%) (odds ratio: 2.31, 95% confidence interval: 1.16\u20134.62, p &lt; 0.05). There were statistically more patients who had 30-day all-cause mortality in SG (5.3%) compared to OG (0%) (p &lt; 0.05). Furthermore, 30-day readmission due to DFI in SG (26.6%) was higher compared to OG (11.6%) (p &lt; 0.05). Empiric escalation of IV antibiotics was required for 14.9% patients in SG and 6.3% patients in OG (p = 0.06). There was no statistical difference for lower limb amputation (p = 0.72), length of hospitalisation (p = 0.13), and the occurrence of safety outcomes in both groups. Conclusions: This study suggests IVCA 1.2 g Q6H is associated with the decreased likelihood of clinical deterioration and is likely as safe as IVCA 1.2 g Q8H. The optimised dose of IVCA may help reduce the use of broad-spectrum antibiotics due to clinical deterioration.<\/jats:p>","DOI":"10.3390\/antibiotics14080758","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimising Regimen of Co-Amoxiclav (ORCA)\u2014The Safety and Efficacy of Intravenous Co-Amoxiclav at Higher Dosing Frequency in Patients with Diabetic Foot Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3720-7384","authenticated-orcid":false,"given":"Jun Jie","family":"Tan","sequence":"first","affiliation":[{"name":"Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peijun Yvonne","family":"Zhou","sequence":"additional","affiliation":[{"name":"Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7525-1319","authenticated-orcid":false,"given":"Jia Le","family":"Lim","sequence":"additional","affiliation":[{"name":"Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Southwest Hospital of Army Medical University, Chongqing 400038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lay Hoon Andrea","family":"Kwa","sequence":"additional","affiliation":[{"name":"Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Diabetes Collaborators (2023). 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