{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:06:56Z","timestamp":1791979616370,"version":"4.4.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), Department of Health and Human Services","award":["75A50122C00080"],"award-info":[{"award-number":["75A50122C00080"]}]},{"name":"Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), Department of Health and Human Services","award":["HHSO100201900007C"],"award-info":[{"award-number":["HHSO100201900007C"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2025,9,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The investigational \u03b2-lactam\/\u03b2-lactamase inhibitor combination cefepime-taniborbactam is intended as therapy for serious infections caused by Gram-negative pathogens resistant to third-generation cephalosporins and carbapenems. Establishing a susceptibility testing reference method for cefepime-taniborbactam that conforms to the Clinical Laboratory Standards Institute (CLSI) M07 and International Standards Organization 20776-1:2019 standards is necessary to inform patient care. This study describes the reference broth microdilution MIC method for cefepime-taniborbactam (taniborbactam fixed at 4 \u00b5g\/mL). In a CLSI M23 Tier 2 study that included nine clinical microbiology laboratories, the CTX-M-15-producer\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      NCTCC 13353 was determined to be appropriate for routine quality control (QC) as ranges for cefepime (\u226564 \u00b5g\/mL) and cefepime-taniborbactam (0.12 to 1 \u00b5g\/mL) were non-overlapping, thereby simultaneously controlling for cefepime antibacterial activity and taniborbactam \u03b2-lactamase inhibition. Of the cefepime-taniborbactam MIC results obtained, 99.6% (269\/270) were within the identified QC range; similarly, 100% (79\/79) and 98.0% (98\/100) of the QC values from a surveillance study and from the two central microbiology laboratories of the CERTAIN-1 Phase 3 clinical study (clintrials.gov identifier NCT03840148) were in range, respectively. Modifications to the standard medium (pH, cation content, or supplementation with human serum, albumin, polysorbate-80, or pulmonary surfactant) or assay parameters (inoculum density, incubation duration, and atmosphere) revealed that only inoculum titers (e.g., \u22655 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      CFU\/mL) exceeding the CLSI M07 standard (2\u20138 \u00d7 10\n                      <jats:sup>5<\/jats:sup>\n                      CFU\/mL) increased MIC values above the QC range. These results demonstrate the robustness and reliability of the cefepime-taniborbactam broth microdilution MIC reference method when performed following the approved standards.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study focuses on a new antibiotic combination called cefepime-taniborbactam that is being developed to treat serious infections caused by bacteria that are often resistant to current treatments. To make sure this new antibiotic combination can be used safely and effectively once it has been approved for clinical use, we developed a standardized laboratory method to measure its activity against certain bacteria that are widely used during quality control testing. The method was assessed in multiple labs and proved to be reliable, accurate, and consistent. It also held up well under different testing conditions, showing that it is a dependable tool for guiding treatment decisions. This is an important step in meeting the challenge of antibiotic-resistant infections since it will help clinicians evaluate cefepime-taniborbactam as a potential treatment option as they strive to improve the care of patients suffering from serious infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jcm.00661-25","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:03:23Z","timestamp":1755608603000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Establishing the reference broth microdilution MIC method for cefepime-taniborbactam"],"prefix":"10.1128","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-5938","authenticated-orcid":false,"given":"Adam","family":"Belley","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Venatorx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Cusick","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Venatorx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6684-6485","authenticated-orcid":false,"given":"Dan C.","family":"Pevear","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Venatorx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2885-6129","authenticated-orcid":true,"given":"Laura","family":"Koeth","sequence":"additional","affiliation":[{"name":"Laboratory Specialists Inc","place":["Westlake, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanna","family":"DiFranco-Fisher","sequence":"additional","affiliation":[{"name":"Laboratory Specialists Inc","place":["Westlake, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimmi","family":"Kothari","sequence":"additional","affiliation":[{"name":"International Health Management Associates Europe S\u00e0rl","place":["Monthey, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-0767","authenticated-orcid":false,"given":"Stephen","family":"Hawser","sequence":"additional","affiliation":[{"name":"International Health Management Associates Europe S\u00e0rl","place":["Monthey, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7827-7227","authenticated-orcid":true,"given":"Greg","family":"Moeck","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Venatorx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad499"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000001074"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae403"},{"key":"e_1_3_3_5_2","volume-title":"WHO Bacterial Priority Pathogens List, 2024","year":"2024","unstructured":"2024. WHO Bacterial Priority Pathogens List, 2024. WHO Bacterial Priority Pathogens List."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13030285"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00115-20"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01518"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01963-19"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00751-24"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae329"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa373"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac446"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304748"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00236-24"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01886-22"},{"key":"e_1_3_3_17_2","volume-title":"CLSI supplement M100. Clinical Laboratory Standards Institute","author":"CLSI","year":"2024","unstructured":"CLSI. 2024. Performance Standards for Antimicrobial Susceptibility Testing. In CLSI supplement M100. Clinical Laboratory Standards Institute, 34th ed","edition":"34"},{"key":"e_1_3_3_18_2","volume-title":"CLSI standard M07. Clinical Laboratory Standards Institute","author":"CLSI","year":"2024","unstructured":"CLSI. 2024. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. In CLSI standard M07. Clinical Laboratory Standards Institute, 12th ed","edition":"12"},{"key":"e_1_3_3_19_2","volume-title":"International Organization for Standardization","author":"ISO","year":"2019","unstructured":"ISO. 2019. 20776\u20131: Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility devices. In International Organization for Standardization. Geneva, Switzerland."},{"key":"e_1_3_3_20_2","volume-title":"CLSI guideline M23. Clinical Laboratory Standards Institute","author":"CLSI","year":"2023","unstructured":"CLSI. 2023. Development of In Vitro Susceptibility Test Methods, Breakpoints, and Quality Control Parameters. In CLSI guideline M23. Clinical Laboratory Standards Institute, 6th ed","edition":"6"},{"key":"e_1_3_3_21_2","first-page":"1","article-title":"ISO","author":"Geneva S","year":"2019","unstructured":"Geneva S. 2019. ISO. ISO:1\u201320776.","journal-title":"ISO"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/430352"},{"key":"e_1_3_3_23_2","volume-title":"CLSI supplement M100. CLSI M100 Performance Standards for Antimicrobial Susceptibility Testing","year":"2024","unstructured":"Performance Standards for Antimicrobial Susceptibility Testing. 2024. In CLSI supplement M100. CLSI M100 Performance Standards for Antimicrobial Susceptibility Testing, 34th ed","edition":"34"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz226"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3548-3554.2001"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00433-18"}],"container-title":["Journal of Clinical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jcm.00661-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jcm.00661-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T13:01:21Z","timestamp":1757509281000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jcm.00661-25"}},"subtitle":[],"editor":[{"given":"Patricia J.","family":"Simner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,10]]}},"alternative-id":["10.1128\/jcm.00661-25"],"URL":"https:\/\/doi.org\/10.1128\/jcm.00661-25","relation":{},"ISSN":["0095-1137","1098-660X"],"issn-type":[{"value":"0095-1137","type":"print"},{"value":"1098-660X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00661-25"}}