125 https://icjournal.org ABSTRACT Background: The use of antibiotics in diabetic foot ulcer infections (DFUI) is essential in reducing morbidity. Optimal administration of antibiotics can improve clinical outcomes and reduce the risk of antibiotic resistance. This study aims to review the efcacy, in terms of clinical cure, of various regimens and the duration of antibiotic administration in DFUI patients, based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The efcacy based on microbiological response is also reviewed as the secondary outcome. Materials and Methods: We used three databases, namely PubMed, Scopus, and ScienceDirect, to search for randomized controlled trials (RCTs) in patients with DFUI who required antibiotics. Results: A total of 16 studies were included in the systematic review. The study locations and bacterial patterns varied, with the most common pathogen being Staphylococcus aureus. Most studies did not demonstrate a signifcant diference in clinical cure and pathogen eradication, either in the comparison between systemic and topical antibiotics or in the duration of administration. Some studies had similar characteristics and were analyzed to conclude. These studies showed that ertapenem had comparable efcacy to piperacillin/tazobactam. Similar results were also conducted from studies of piperacillin-tazobactam+amoxicillin- clavulanic acid vs. moxifoxacin. Conclusion: Most studies have heterogeneous characteristics, possibly due to diferences in research location. Therefore, there is no strong evidence to recommend a specifc antibiotic with the highest efcacy. However, since all included studies are RCTs, this review provides a good summary in considering antibiotic choices when treating DFUI patients. Keywords: Antibiotics; Diabetic foot ulcer; Infection; Randomized controlled trial; Systematic review INTRODUCTION Diabetes mellitus (DM) is a serious long-term disease that has a major impact on the lives and well-being of individuals, families, and communities around the world. The global Infect Chemother. 2022 Mar;54(1):125-139 https://doi.org/10.3947/ic.2021.0144 pISSN 2093-2340·eISSN 2092-6448 Original Article Received: Dec 15, 2021 Accepted: Feb 19, 2022 Published online: Mar 16, 2022 Corresponding Author: Rani Sauriasari, B.Pharm., M.Med.Sci., PhD Faculty of Pharmacy, Universitas Indonesia, A Building 3rd Floor, Kampus Baru UI Depok, 16424, West Java Province, Indonesia. Tel: +62-1-727-0031 Fax: +62-1-786-3433 Email: rani@farmasi.ui.ac.id Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https:// creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Vincent Pratama https://orcid.org/0000-0002-6976-9024 Hindun Wilda Risni https://orcid.org/0000-0002-8000-6992 Em Yunir https://orcid.org/0000-0002-2004-9050 Rani Sauriasari https://orcid.org/0000-0001-7861-4369 Funding This work was supported by PDUPT Grant No. NKB-064/UN2.RST/HKP.05.00/2021. Vincent Pratama 1 , Hindun Wilda Risni 1 , Em Yunir 2 , and Rani Sauriasari 1 1 Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia 2 Division of Endocrinology, Department of Internal Medicine Dr. Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia A Systematic Review of Randomized Controlled Trials of Antibiotic Use in Diabetic Foot Ulcer Infections: Focus on Clinical Cure