{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:53:00Z","timestamp":1791175980167,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Carbapenem-resistant Gram-negative bacilli are an increasing threat in diabetic foot ulcer (DFU) infections, limiting therapeutic options and worsening outcomes. However, data linking specific carbapenemase genes to clinical and metabolic factors remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To isolate Gram-negative bacilli from deep tissue biopsies of DFUs, determine carbapenem susceptibility by minimum inhibitory concentration (MIC) testing, detect major carbapenemase genes by multiplex qPCR, and evaluate their association with glycemic control and Wagner grade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross-sectional study included 150 patients with infected DFUs. Isolates recovered from tissue and other specimens were identified by standard microbiological methods, and carbapenem susceptibility was assessed by MIC testing. Multiplex qPCR was used to detect\n                      <jats:italic>bla<\/jats:italic>\n                      KPC,\n                      <jats:italic>bla<\/jats:italic>\n                      NDM,\n                      <jats:italic>bla<\/jats:italic>\n                      OXA-48,\n                      <jats:italic>bla<\/jats:italic>\n                      VIM, and\n                      <jats:italic>bla<\/jats:italic>\n                      IMP, and associations between resistance determinants and clinical variables were analyzed statistically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean patient age was 56.4 \u00b1 9.8 years, with a male predominance (61.3%), and high-grade ulcers (Wagner III\u2013V) were present in 54.7% of patients.\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      predominated (60.0%), followed by\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      (each 14.7%). Resistance to meropenem and imipenem was high (77.3% and 75.3%, respectively), and carbapenemase production was detected in 84.0% of isolates.\n                      <jats:italic>bla<\/jats:italic>\n                      KPC (28.0%) and\n                      <jats:italic>bla<\/jats:italic>\n                      NDM (24.0%) were the most prevalent genes and were significantly associated with phenotypic carbapenemase production (P\u00a0=\u00a00.002 and P\u00a0=\u00a00.006, respectively). Carbapenemase producers showed significantly higher fasting glucose and HbA1c levels than non-producers (P &amp;lt; 0.001), with no significant association observed for Wagner grade (P\u00a0=\u00a00.570).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DFUs showed a high burden of carbapenemase-producing Gram-negative bacilli, driven mainly by\n                      <jats:italic>bla<\/jats:italic>\n                      KPC and\n                      <jats:italic>bla<\/jats:italic>\n                      NDM. Poor glycemic control was strongly associated with these resistant infections, underscoring the need for integrated metabolic management, molecular surveillance, and antimicrobial stewardship. These findings position glycemic control as a modifiable driver of antimicrobial resistance in DFUs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1847743","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:32:42Z","timestamp":1791174762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular epidemiology of carbapenemase-producing gram-negative bacilli in diabetic foot infections: association with glycemic control"],"prefix":"10.3389","volume":"16","author":[{"given":"Gamal","family":"Othman","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelnaser","family":"A. Badawy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Northern Border University","place":["Arar, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Hamed Al-Serwi","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysaa","family":"El Sayed Zaki","sequence":"additional","affiliation":[{"name":"Clinical Pathology-Mansoura Faculty of Medicine, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha","family":"Tharwat Abou El-khier","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology- Mansoura Faculty of Medicine, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashwa M.","family":"Alkassaby","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology- Mansoura Faculty of Medicine, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Saleh Ismail","sequence":"additional","affiliation":[{"name":"Clinical Pathology-Mansoura Faculty of Medicine, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13061343","article-title":"Multidrug-resistant infections and metabolic syndrome: an overlooked bidirectional relationship","volume":"13","author":"Acierno","year":"2025","journal-title":"Biomedicines"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1038\/s41598-025-33134-z","article-title":"Microbiological profile and antimicrobial resistance in diabetic foot infections: a cross-sectional study from a low- to middle-income country","volume":"16","author":"Arjan","year":"2025","journal-title":"Sci. Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2019.00074","article-title":"Treatment of infections due to MDR Gram-negative bacteria","volume":"6","author":"Bassetti","year":"2019","journal-title":"Front. Med. (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"442","DOI":"10.2174\/1573399815666191024085838","article-title":"Type 2 diabetes and its impact on the immune system","volume":"16","author":"Berbudi","year":"2020","journal-title":"Curr. Diabetes Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.18593\/eba.27178","article-title":"Clinical and microbiological characteristics of diabetic foot infection by carbapenem-resistant bacteria in a hospital in southern Brazil","volume":"23","author":"Braun","year":"2023","journal-title":"Evid\u00eancia"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.4103\/2230-8210.94253","article-title":"Infections in patients with diabetes mellitus: a review of pathogenesis","volume":"16","author":"Casqueiro","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"B8","volume-title":"Antibiotic Resistance Threats in the United States","year":"2024"},{"key":"B9","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing. 35th Ed. CLSI Supplement M100","year":"2025"},{"key":"B10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.3390\/antibiotics13070599","article-title":"Bacterial profile and antimicrobial resistance patterns of diabetic foot infections","volume":"13","author":"Co\u015fkun","year":"2024","journal-title":"Antibiotics (Basel)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00509-23","article-title":"Triple threat: how diabetes results in worsened bacterial infections","volume":"92","author":"Darwitz","year":"2024","journal-title":"Infect. Immun."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.95291","article-title":"Clinico-microbiological profile of diabetic foot ulcers","volume":"17","author":"Das","year":"2025","journal-title":"Cureus"},{"key":"B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1590\/0100-3984.2021.0010","article-title":"Moyamoya disease and syndrome: a review","volume":"55","author":"Demartini","year":"2022","journal-title":"Radiol. Bras."},{"key":"B14","volume-title":"Carbapenem-Resistant Enterobacterales, Second Update","year":"2024"},{"key":"B15","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/nyas.13569","article-title":"Update on management of diabetic foot ulcers","volume":"1411","author":"Everett","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B16","first-page":"475","article-title":"Role of OmpK35 and OmpK36 alterations in carbapenem resistance","volume":"52","author":"Hamzaoui","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B17","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ijantimicag.2018.05.018","article-title":"Role of OmpK35 and OmpK36 alterations in carbapenem resistance in Klebsiella pneumoniae","volume":"52","author":"Hamzaoui","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B18","first-page":"24","article-title":"\u03b2-lactamase-producing pathogens in diabetic foot infections","volume":"4","author":"Khan","year":"2025","journal-title":"Microbiol. Res."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms13102311","article-title":"Multifaceted antibiotic resistance in diabetic foot infections: a systematic review","volume":"13","author":"Li","year":"2025","journal-title":"Microorganisms"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms13102311","article-title":"Multifaceted antibiotic resistance in diabetic foot infections: systematic review","volume":"13","author":"Li","year":"2025","journal-title":"Microorganisms"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1357289","article-title":"Molecular characteristics and phenotypic detection of carbapenemases by whole genome sequencing","volume":"14","author":"Liang","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1357289","article-title":"Molecular characteristics and evaluation of phenotypic detection of carbapenemases among Enterobacterales and Pseudomonas aeruginosa via whole genome sequencing","volume":"14","author":"Liang","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3280","article-title":"Guidelines on diagnosis and treatment of foot infection in persons with diabetes","volume":"36","author":"Lipsky","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.2147\/IDR.S359157","article-title":"Risk factors for multidrug-resistant organisms infection in diabetic foot ulcer","volume":"15","author":"Liu","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"B25","doi-asserted-by":"crossref","first-page":"1393309","DOI":"10.3389\/fcdhc.2024.1393309","article-title":"Microbial patterns and resistance trends in diabetic foot infections: a systematic review","volume":"5","author":"Maity","year":"2024","journal-title":"Front. Clin. Diabetes Healthc"},{"key":"B26","doi-asserted-by":"publisher","first-page":"72","DOI":"10.2174\/1874285801307010072","article-title":"A simple method for assessment of MDR bacteria for over-expressed efflux pumps","volume":"7","author":"Martins","year":"2013","journal-title":"Open Microbiol. J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1093\/jac\/dkr563","article-title":"Rapid detection of carbapenemase genes by multiplex real-time PCR","volume":"67","author":"Monteiro","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1099\/00221287-148-1-257","article-title":"Determination of bacterial load by real-time PCR using universal 16S rRNA gene primers","volume":"148","author":"Nadkarni","year":"2002","journal-title":"Microbiology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/KKPP0404","article-title":"Swabs versus tissue samples for infected diabetic foot ulcers","volume":"29","author":"Nelson","year":"2025","journal-title":"Health Technol. Assess."},{"key":"B30","doi-asserted-by":"publisher","first-page":"70","DOI":"10.64294\/jsd.v3i4.193","article-title":"High prevalence of multidrug-resistant bacteria in diabetic foot infections: a series of 59 cases at a district hospital in Cameroon","volume":"3","author":"Ngono","year":"2025","journal-title":"J. Sci. Dis."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.52468","article-title":"Carbapenemase-producing Klebsiella pneumoniae infections in diabetic and non-diabetic patients","volume":"16","author":"Pattolath","year":"2024","journal-title":"Cureus"},{"key":"B32","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/dmrr.2400","article-title":"Diabetic foot disease: impact of ulcer location on ulcer healing","volume":"29","author":"Pickwell","year":"2013","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/dmrr.2400","article-title":"Impact of ulcer location on prognosis","volume":"29","author":"Pickwell","year":"2013","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.diagmicrobio.2010.12.002","article-title":"Multiplex PCR for detection of acquired carbapenemase genes","volume":"70","author":"Poirel","year":"2011","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s00125-006-0491-1","article-title":"High prevalence of ischemia, infection, and serious comorbidity in patients with diabetic foot disease","volume":"50","author":"Prompers","year":"2007","journal-title":"Diabetologia"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.67824","article-title":"Prevalence and antibiotic resistance of Klebsiella pneumoniae in diabetic foot ulcer","volume":"16","author":"P SR","year":"2024","journal-title":"Cureus"},{"key":"B37","first-page":"1456","article-title":"Prevalence and antibiotic resistance of Serratia marcescens in chronic wound infections","volume":"18","author":"Reddy","year":"2024","journal-title":"J. Infect. Dev. Ctries"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15020141","article-title":"Prevalence and molecular characterization of carbapenemase-producing multidrug-resistant bacteria in diabetic foot ulcer infections","volume":"15","author":"Saleem","year":"2025","journal-title":"Diagnost. (Basel)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3657","article-title":"Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update)","volume":"40","author":"Schaper","year":"2024","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113089","article-title":"COVID-19 and diabetes: Association intensifies risk factors for morbidity and mortality","volume":"151","author":"Singh","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B41","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1186\/s12879-024-09747-6","article-title":"Prevalence of carbapenem-resistant gram-negative bacteria in Africa: systematic review and meta-analysis","volume":"24","author":"Sisay","year":"2024","journal-title":"BMC Infect. Dis."},{"key":"B42","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1186\/s12879-025-10959-7","article-title":"Prevalence of genes encoding carbapenem resistance in Klebsiella pneumoniae in Africa","volume":"25","author":"Sisay","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1186\/s12879-025-10959-7","article-title":"Prevalence of genes encoding carbapenem resistance in Klebsiella pneumoniae recovered from clinical samples in Africa: systematic review and meta-analysis","volume":"25","author":"Sisay","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B44","first-page":"62","article-title":"Mechanisms of carbapenem resistance in Pseudomonas aeruginosa","volume":"20","author":"Solgi","year":"2021","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B45","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12941-021-00466-9","article-title":"Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa","volume":"20","author":"Solgi","year":"2021","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae403","article-title":"Infectious Diseases Society of America guidance on the treatment of antimicrobial-resistant Gram-negative infections","author":"Tamma","year":"2024","journal-title":"Clin. Infect. Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae403","article-title":"Infectious Diseases Society of America guidance on treatment of antimicrobial-resistant Gram-negative infections","author":"Tamma","year":"2024","journal-title":"Clin. Infect. Dis"},{"key":"B48","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3855\/jidc.1977","article-title":"Microbiological and clinical characteristics of diabetic foot infections in northern India","volume":"6","author":"Tiwari","year":"2012","journal-title":"J. Infect. Dev. Ctries"},{"key":"B49","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1067\/mva.2001.117151","article-title":"Adult Moyamoya disease with peripheral artery involvement","volume":"34","author":"Weber","year":"2001","journal-title":"J. Vasc. Surg."},{"key":"B50","volume-title":"Global Antimicrobial Resistance Surveillance System (GLASS) Report","year":"2024"},{"key":"B51","volume-title":"WHO Bacterial Priority Pathogens List 2024","year":"2024"},{"key":"B52","doi-asserted-by":"publisher","first-page":"7092","DOI":"10.1038\/s41598-025-91034-8","article-title":"Characterization of pathogenic microorganisms in diabetic foot infections and predictive nomogram analysis","volume":"15","author":"Yan","year":"2025","journal-title":"Sci. Rep."},{"key":"B53","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12902-022-00957-0","article-title":"Analysis of risk factors for multidrug-resistant organisms in diabetic foot infection","volume":"22","author":"Yan","year":"2022","journal-title":"BMC Endocr. Disord."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13090845","article-title":"Characterization of microbial profiles and antimicrobial resistance patterns in diabetic foot infections","volume":"13","author":"Zhang","year":"2024","journal-title":"Antibiotics (Basel)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global epidemiology of diabetic foot ulceration","volume":"49","author":"Zhang","year":"2017","journal-title":"Ann. Med."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1690417","article-title":"Global trends in carbapenem-resistant Gram-negative bacteria: a bibliometric analysis from 2020 to 2025","volume":"15","author":"Zhang","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1847743\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:33:00Z","timestamp":1791174780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1847743\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":56,"alternative-id":["10.3389\/fcimb.2026.1847743"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1847743","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1847743"}}