{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:37:45Z","timestamp":1791265065480,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"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>Diabetic foot infections (DFIs) are a common complication of diabetes; however, there is clinical uncertainty regarding the optimal antimicrobial selection. The aim of this review was to critically evaluate the recent systematic reviews on the efficacy and safety of systemic (parenteral or oral) antimicrobials for DFI. Medline, Embase, CENTRAL, and CINAHL databases and the PROSPERO register were searched from January 2015 to January 2023. Systematic reviews with or without meta-analyses on systemic antimicrobials for DFI, with outcomes of clinical infection resolution or complications, were included. Of the 413 records identified, 6 systematic reviews of 29 individual studies were included. Heterogeneity of individual studies precluded meta-analysis, except for ertapenem versus piperacillin\u2013tazobactam (RR 1.07, 95% CI [0.96\u20131.19]) and fluoroquinolones versus piperacillin\u2013tazobactam (RR 1.03, 95% CI [0.89\u20131.20]) in one review. The application of the AMSTAR-2 tool determined two reviews to be of high quality. There was no statistical difference in the clinical resolution of infections for 24 different antimicrobial regimens (penicillins, cephalosporins, carbapenems, fluoroquinolones, vancomycin, metronidazole, clindamycin, linezolid, daptomycin, and tigecycline). However, tigecycline did not meet non-inferiority against ertapenem \u00b1 vancomycin (absolute difference \u22125.5%, 95% CI [\u221211.0\u20130.1]) and was associated with a higher incidence of adverse drug events. There is minimal systematic review evidence to suggest one regimen is superior to another for DFI.<\/jats:p>","DOI":"10.3390\/antibiotics12061041","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T01:35:30Z","timestamp":1686620130000},"page":"1041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Systemic Antimicrobial Therapy for Diabetic Foot Infections: An Overview of Systematic Reviews"],"prefix":"10.3390","volume":"12","author":[{"given":"Angela","family":"Wright","sequence":"first","affiliation":[{"name":"Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia"},{"name":"Pharmacy Department, Mackay Base Hospital, Mackay, QLD 4740, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Wood","sequence":"additional","affiliation":[{"name":"Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janath","family":"De Silva","sequence":"additional","affiliation":[{"name":"Medicine Department, Mackay Base Hospital, Mackay, QLD 4740, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Simon","family":"Bell","sequence":"additional","affiliation":[{"name":"Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3280","DOI":"10.1002\/dmrr.3280","article-title":"Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update)","volume":"36","author":"Lipsky","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1185\/03007995.2015.1128888","article-title":"Current and emerging therapies in the management of diabetic foot ulcers","volume":"32","author":"Karri","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_3","unstructured":"Antibiotic Expert Group (2019). Therapeutic Guidelines: Antibiotic, Therapeutic Guidelines Limited. Available online: https:\/\/www.tg.org.au."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Macdonald, K.E., Boeckh, S., Stacey, H.J., and Jones, J.D. (2021). The microbiology of diabetic foot infections: A meta-analysis. BMC Infect Dis., 21.","DOI":"10.1186\/s12879-021-06516-7"},{"key":"ref_5","unstructured":"National Institute of Health and Care Excellence (2019). Diabetic Foot Problems: Prevention and Management [NG19], NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ng19."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1093\/cid\/cis346","article-title":"2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections","volume":"54","author":"Lipsky","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Smith, V., Devane, D., Begley, C.M., and Clarke, M. (2011). Methodology in conducting a systematic review of systematic reviews of healthcare interventions. BMC Med. Res. Methodol., 11.","DOI":"10.1186\/1471-2288-11-15"},{"key":"ref_8","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2022). Cochrane Handbook for Systematic Reviews of Interventions, Cochrane. Available online: www.training.cochrane.org\/handbook."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.5195\/jmla.2017.183","article-title":"Updating search strategies for systematic reviews using EndNote","volume":"105","author":"Bramer","year":"2017","journal-title":"J. Med. Libr. Assoc."},{"key":"ref_11","first-page":"CD009061","article-title":"Systemic antibiotics for treating diabetic foot infections","volume":"9","author":"Sola","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"j4008","DOI":"10.1136\/bmj.j4008","article-title":"AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both","volume":"358","author":"Shea","year":"2017","journal-title":"BMJ"},{"key":"ref_13","unstructured":"National Institute of Health and Care Excellence (2019). Diabetic Foot Infection: Antimicrobial Prescribing, Evidence Review [NG19], NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ng19\/evidence."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e3282","DOI":"10.1002\/dmrr.3282","article-title":"Interventions in the management of infection in the foot in diabetes: A systematic review","volume":"36","author":"Peters","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/wrr.12649","article-title":"Antibiotic therapy of diabetic foot infections: A systematic review of randomized controlled trials","volume":"26","author":"Tchero","year":"2018","journal-title":"Wound Repair Regen."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tardaguila-Garcia, A., Sanz-Corbalan, I., Garcia-Alamino, J.M., Ahluwalia, R., Uccioli, L., and Lazaro-Martinez, J.L. (2021). Medical versus surgical treatment for the management of diabetic foot osteomyelitis: A systematic review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061237"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3947\/ic.2021.0144","article-title":"A Systematic Review of Randomized Controlled Trials of Antibiotic Use in Diabetic Foot Ulcer Infections: Focus on Clinical Cure","volume":"54","author":"Pratama","year":"2022","journal-title":"Infect. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ijantimicag.2005.07.017","article-title":"Sequential intravenous\/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection","volume":"26","author":"Giordano","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s15010-012-0367-x","article-title":"Efficacy and safety of IV\/PO moxifloxacin and IV piperacillin\/tazobactam followed by PO amoxicillin\/clavulanic acid in the treatment of diabetic foot infections: Results of the RELIEF study","volume":"41","author":"Schaper","year":"2013","journal-title":"Infection"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/jac\/dkm130","article-title":"Treating diabetic foot infections with sequential intravenous to oral moxifloxacin compared with piperacillin\u2013tazobactam\/amoxicillin\u2013clavulanate","volume":"60","author":"Lipsky","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1128\/AAC.45.2.525-531.2001","article-title":"Clinafloxacin versus piperacillin-tazobactam in treatment of patients with severe skin and soft tissue infections","volume":"45","author":"Siami","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1086\/341026","article-title":"Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: A randomized, open-label trial","volume":"35","author":"Graham","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s15010-009-8468-x","article-title":"Efficacy and safety of sequential intravenous\/oral moxifloxacin vs intravenous\/oral amoxicillin\/clavulanate for complicated skin and skin structure infections","volume":"37","author":"Arvis","year":"2009","journal-title":"Infection"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/clind\/24.4.643","article-title":"Antibiotic therapy for diabetic foot infections: Comparison of two parenteral-to-oral regimens","volume":"24","author":"Lipsky","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1093\/jac\/dkw004","article-title":"Ertapenem versus piperacillin\/tazobactam for diabetic foot infections in China: A Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial","volume":"71","author":"Xu","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1086\/340348","article-title":"Ertapenem once daily versus piperacillin-tazobactam 4 times per day for treatment of complicated skin and skin-structure infections in adults: Results of a prospective, randomized, double-blind multicenter study","volume":"34","author":"Graham","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/S0140-6736(05)67694-5","article-title":"Ertapenem versus piperacillin\/tazobactam for diabetic foot infections (SIDESTEP): Prospective, randomised, controlled, double-blinded, multicentre trial","volume":"366","author":"Lipsky","year":"2005","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0924-8579(96)00305-6","article-title":"Treatment of diabetic foot infection: An open randomised comparison of imipenem\/cilastatin and piperacillin\/clindamycin combination therapy","volume":"7","author":"Bouter","year":"1996","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1089\/sur.2005.6.27","article-title":"An open-label, randomized study comparing efficacy and safety of intravenous piperacillin\/tazobactam and ampicillin\/sulbactam for infected diabetic foot ulcers","volume":"6","author":"Harkless","year":"2005","journal-title":"Surg. Infect. (Larchmt.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1469-0691.2009.03067.x","article-title":"Piperacillin\/tazobactam versus imipenem\/cilastatin for severe diabetic foot infections: A prospective, randomized clinical trial in a university hospital","volume":"16","author":"Saltoglu","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/clinids\/18.5.683","article-title":"Use of ampicillin\/sulbactam versus imipenem\/cilastatin in the treatment of limb-threatening foot infections in diabetic patients","volume":"18","author":"Grayson","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/(SICI)1096-9136(199602)13:2<156::AID-DIA59>3.0.CO;2-U","article-title":"Antibiotic treatment for uncomplicated neuropathic forefoot ulcers in diabetes: A controlled trial","volume":"13","author":"Chantelau","year":"1996","journal-title":"Diabet. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1128\/AAC.37.8.1580","article-title":"Treatment of hospitalized patients with complicated skin and skin structure infections: Double-blind, randomized, multicenter study of piperacillin-tazobactam versus ticarcillin-clavulanate. The Piperacillin\/Tazobactam Skin and Skin Structure Study Group","volume":"37","author":"Tan","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1177\/153857449703100403","article-title":"Prospective, Randomized Comparison of Ampicillin\/Sulbactam and Cefoxitin for Diabetic Foot Infections","volume":"31","author":"Erstad","year":"1997","journal-title":"J. Vasc. Surg."},{"key":"ref_35","first-page":"63","article-title":"Ceftriaxone treatment of skin and soft tissue infections in a once daily regimen","volume":"77","author":"Bradsher","year":"1984","journal-title":"Am. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.amjopharm.2004.09.006","article-title":"Clinical efficacy, tolerability, and cost savings associated with the use of open-label metronidazole plus ceftriaxone once daily compared with ticarcillin\/clavulanate every 6 hours as empiric treatment for diabetic lower-extremity infections in older males","volume":"2","author":"Clay","year":"2004","journal-title":"Am. J. Geriatr. Pharmacother."},{"key":"ref_37","first-page":"156","article-title":"Antibiotic therapy for diabetic foot infections: Comparison of cephalosporines with chinolones","volume":"17","author":"Lobmann","year":"2004","journal-title":"Diabetes Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.18203\/2319-2003.ijbcp20163145","article-title":"Comparison of efficacy of levofloxacin-metronidazole combination versus ceftriaxone in cases of moderate diabetic foot infection","volume":"5","author":"Patil","year":"2016","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1086\/526527","article-title":"A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections","volume":"46","author":"Noel","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","first-page":"36","article-title":"Treatment and long-term follow-up of foot infections in patients with diabetes or ischemia: A randomized, prospective, double-blind comparison of cefoxitin and ceftizoxime","volume":"10","author":"Hughes","year":"1987","journal-title":"Clin. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/0002-9343(83)90103-1","article-title":"Amdinocillin plus cefoxitin versus cefoxitin alone in therapy of mixed soft tissue infections (including diabetic foot infections)","volume":"75","author":"File","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1001\/archinte.1990.00390160058013","article-title":"Outpatient management of uncomplicated lower-extremity infections in diabetic patients","volume":"150","author":"Lipsky","year":"1990","journal-title":"Arch. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1086\/420818","article-title":"The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections","volume":"38","author":"Arbeit","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/jac\/dkh531","article-title":"Daptomycin for treating infected diabetic foot ulcers: Evidence from a randomized, controlled trial comparing daptomycin with vancomycin or semi-synthetic penicillins for complicated skin and skin-structure infections","volume":"55","author":"Lipsky","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.diagmicrobio.2013.12.007","article-title":"Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis","volume":"78","author":"Lauf","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1086\/380449","article-title":"Treating foot infections in diabetic patients: A randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam\/amoxicillin-clavulanate","volume":"38","author":"Lipsky","year":"2004","journal-title":"Clin. Infect. Dis."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/6\/1041\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:53:07Z","timestamp":1760125987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/6\/1041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,12]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["antibiotics12061041"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12061041","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,12]]}}}