{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:13:08Z","timestamp":1791825188545,"version":"4.3.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004625","name":"Universiti Teknologi MARA","doi-asserted-by":"publisher","award":["600-RMC\/KEPU 5\/3 (011\/2023)"],"award-info":[{"award-number":["600-RMC\/KEPU 5\/3 (011\/2023)"]}],"id":[{"id":"10.13039\/501100004625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Knowledge gap on the susceptibility of novel \u03b2-lactam agents (cefiderocol, ceftazidime-avibactam, imipenem-cilastatin-relebectam, and aztreonam) against carbapenem-resistant Enterobacterales (CRE) has been recognized. This study aimed to genotypically characterize CRE isolates and investigate the novel \u03b2-lactam activity against CRE. CRE is defined as Enterobacterales that is phenotypically non-susceptible to any carbapenems, including imipenem, meropenem, and ertapenem. A total of 154 CRE isolates were collected from two tertiary centers in Malaysia from October 2023 to May 2024. Carbapenemase-producing genes (\n bla<\/jats:italic>\n NDM<\/jats:sub>\n ,\n bla<\/jats:italic>\n OXA-48<\/jats:sub>\n ,\n bla<\/jats:italic>\n KPC<\/jats:sub>\n ,\n bla<\/jats:italic>\n VIM<\/jats:sub>\n , and\n bla<\/jats:italic>\n IMP<\/jats:sub>\n ,) were detected using PCR. Susceptibility to \u03b2-lactams was determined using disc diffusion. Of 154 CRE isolates, 102 (66.2%) were carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE).\n bla<\/jats:italic>\n NDM<\/jats:sub>\n (76\/102; 74.5%),\n bla<\/jats:italic>\n OXA-48-like<\/jats:sub>\n (17\/102; 16.7%),\n bla<\/jats:italic>\n NDM<\/jats:sub>\n &\n bla<\/jats:italic>\n OXA-48-like<\/jats:sub>\n (8\/102; 7.8%), and\n bla<\/jats:italic>\n NDM<\/jats:sub>\n &\n bla<\/jats:italic>\n VIM<\/jats:sub>\n (1\/102; 1.0%) were identified among the CP-CRE isolates. The proportion of CRE isolates that exhibited susceptibility towards cefiderocol, ceftazidime-avibactam, and imipenem-cilastatin-relebactam was 86.4% (133\/154), 41.6% (64\/154), and 26.0% (40\/154), respectively. Among\n bla<\/jats:italic>\n NDM<\/jats:sub>\n -harboring isolates, cefiderocol (57\/76; 75.0%) demonstrated superior activity compared with ceftazidime-avibactam (3\/76; 3.9%) and imipenem-cilastatin-relebectam (1\/76; 1.3%). Among isolates harboring\n bla<\/jats:italic>\n OXA-48-like<\/jats:sub>\n , cefiderocol, ceftazidime-avibactam, and imipenem-cilastatin-relebectam demonstrated 100% (17\/17), 70.6% (12\/17), and 17.6% (3\/17) susceptibility, respectively. Nine isolates that harbored two genes (eight\n bla<\/jats:italic>\n NDM<\/jats:sub>\n +\n bla<\/jats:italic>\n OXA-48-like<\/jats:sub>\n , one\n bla<\/jats:italic>\n NDM<\/jats:sub>\n +\n bla<\/jats:italic>\n VIM<\/jats:sub>\n ) demonstrated 100% susceptibility to cefiderocol but 100% resistance to ceftazidime-avibactam and imipenem-cilastatin-relebectam. The ceftazidime-avibactam plus aztreonam combination achieved 100% susceptibility in isolates harboring metallo-\u03b2-lactamases-producing genes;\n bla<\/jats:italic>\n NDM<\/jats:sub>\n (76\/76; 100%),\n bla<\/jats:italic>\n NDM<\/jats:sub>\n +\n bla<\/jats:italic>\n OXA-48-like<\/jats:sub>\n (8\/8; 100%), and\n bla<\/jats:italic>\n NDM<\/jats:sub>\n +\n bla<\/jats:italic>\n VIM<\/jats:sub>\n (1\/1; 100%).\n bla<\/jats:italic>\n NDM<\/jats:sub>\n was the most prevalent gene causing CRE. Cefiderocol has the greatest activity compared with other investigated \u03b2-lactams.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Carbapenem-resistant Enterobacterales (CRE) has been recognized as a priority and public health concern requiring urgent attention for the development of effective antimicrobial resistance (AMR) prevention and control strategies. Differentiating between carbapenemase-producing CRE (CP-CRE) and non-CP-CRE, along with identifying carbapenemase-producing genes, is essential for guiding targeted antibiotic therapy. Among novel \u03b2-lactam agents, cefiderocol and the combination of ceftazidime-avibactam and aztreonam have shown promising activity against\n bla<\/jats:italic>\n NDM<\/jats:sub>\n -producing CRE, supporting precision medicine approaches. Nevertheless, our study observed the emergence of cefiderocol resistance in isolates without prior drug exposure, highlighting a potential challenge in combating AMR.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.00553-25","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:00:37Z","timestamp":1758546037000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Molecular characterization of carbapenem-resistant Enterobacterales (CRE) and\n in vitro<\/i>\n activity of novel beta lactams against CRE isolates from Malaysia"],"prefix":"10.1128","volume":"13","author":[{"given":"Fairuz Abdul","family":"Rashid","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03n0nnh89","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology Unit, Department of Pathology, Hospital Kuala Lumpur","place":["Kuala Lumpur, Malaysia"]},{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology & Parasitology, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurzam","family":"Suhaila Che Hussin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03n0nnh89","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology Unit, Department of Pathology, Hospital Kuala Lumpur","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Fathiyah Zaipul","family":"Anuar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noraziah","family":"Sahlan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology & Parasitology, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navindra Kumari","family":"Palanisamy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology & Parasitology, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]},{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-2515","authenticated-orcid":true,"given":"Fadzilah","family":"Mohd Nor","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology & Parasitology, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]},{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital","place":["Selangor, Malaysia"]},{"id":[{"id":"https:\/\/ror.org\/05n8tts92","id-type":"ROR","asserted-by":"publisher"}],"name":"Integrative Pharmacogenomics Research Institute (i-PROMISE), Level 7, Ff3, Faculty of Pharmacy, Universiti Teknologi MARA","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1199","article-title":"Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050","volume":"404","author":"GBD 2021 Antimicrobial Resistance Collaborators","year":"2021","unstructured":"GBD 2021 Antimicrobial Resistance Collaborators. 2021. 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