{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:52:48Z","timestamp":1791381168920,"version":"4.3.3"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"University of Zurich","id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The limited treatment options for carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      (CRAB)-invasive infections highlight the urgent need for novel therapeutic agents. Zosurabalpin is a first-in-class tethered macrocyclic-peptide targeting the LptB\u2082FGC-complex. In this study, we evaluated the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of zosurabalpin a1gainst a diverse global set of CRAB clinical isolates. We compared zosurabalpin\u2019s activity with currently available antibiotics, including colistin, cefiderocol, sulbactam-durlobactam, as well as rifabutin. Additionally, we assessed different AST methods to support reliable zosurabalpin susceptibility testing. We included a total of 304 CRAB clinical isolates from Switzerland, Israel, Turkey, Ethiopia, Pakistan, and Australia. Among them, 297 carried plasmid-borne-carbapenemases (236 OXA-type-producers, 60 NDM-type-producers alone or in combination with OXA-type-carbapenemases, and 1 GES-14-producer), 3 were GES-ESBL-producers, and 4 isolates were without acquired ESBL\/carbapenemases. We determined zosurabalpin minimal inhibitory concentrations (MICs) by broth microdilution using cation-adjusted Mueller-Hinton broth (CA-MHB) supplemented with 20% heat-inactivated horse serum, in accordance with CLSI recommendations, as well as using plain CA-MHB, with reading at substantial reduction (80% growth inhibition). We determined MICs of the remaining antibiotics according to EUCAST methods: colistin and sulbactam-durlobactam (with fixed durlobactam concentration of 4 mg\/L) with CA-MHB, cefiderocol with iron-depleted CA-MHB, and rifabutin with RPMI. The zosurabalpin MIC distribution using the CLSI-based method ranged from \u22640.032 to 2 mg\/L (MIC\n                      <jats:sub>90<\/jats:sub>\n                      = 0.5 mg\/L), with no CRAB isolates showing MICs displaying MICs suggestive of high-level acquired resistance. A single isolate with MIC = 2 mg\/L harbored a 13-amino-acid deletion in\n                      <jats:italic toggle=\"yes\">lptD<\/jats:italic>\n                      (position 692), potentially affecting outer-membrane LPS biogenesis. MIC\n                      <jats:sub>90<\/jats:sub>\n                      values for cefiderocol, sulbactam\u2013durlobactam, colistin, and rifabutin were 8, 16, 1, and 2 mg\/L, respectively. Zosurabalpin showed no cross-resistance with any of the tested antimicrobials. Zosurabalpin MICs in CRAB isolates were generally low, including metallo-\u03b2-lactamase-producing-CRAB. The low MICs show a high potential to overcome current treatment limitations; however, mutations in\n                      <jats:italic toggle=\"yes\">lptD<\/jats:italic>\n                      may contribute to resistance emergence and should be further studied.\n                    <\/jats:p>\n                    <jats:p\/>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00727-26","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:54:41Z","timestamp":1789570481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    activity of zosurabalpin against a global set of carbapenem-resistant-\n                    <i>A. baumannii<\/i>\n                    clinical isolates"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-5952","authenticated-orcid":true,"given":"Stefano","family":"Mancini","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-5114","authenticated-orcid":true,"given":"Helena M. B.","family":"Seth-Smith","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/002n09z45","id-type":"ROR","asserted-by":"publisher"}],"name":"SIB Swiss Institute of Bioinformatics","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Haldimann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-050X","authenticated-orcid":true,"given":"Jacob","family":"Moran-Gilad","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013v7fk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology Laboratory, Hadassah Hebrew University Medical Center","place":["Jerusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Aktas","sequence":"additional","affiliation":[{"name":"SB\u00dc Hamidiye Etfal Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6znur","family":"G\u00fcne\u015f","sequence":"additional","affiliation":[{"name":"SB\u00dc Hamidiye Etfal Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammedaman","family":"Mama Hussen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zte5g15","id-type":"ROR","asserted-by":"publisher"}],"name":"Goba Referral Hospital, Madda Walabu University","place":["Robe, Ethiopia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-7563","authenticated-orcid":true,"given":"Mark","family":"Willcox","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03r8z3t63","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Optometry and Vision Science, University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeel","family":"Shahzad","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03r8z3t63","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Optometry and Vision Science, University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ali","family":"Syed","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05vtb1235","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Haripur","place":["Haripur, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kolesnik-Goldmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-4723","authenticated-orcid":true,"given":"Tim","family":"Roloff","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/002n09z45","id-type":"ROR","asserted-by":"publisher"}],"name":"SIB Swiss Institute of Bioinformatics","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-0812","authenticated-orcid":true,"given":"Oliver","family":"Nolte","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Egli","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2025.107605"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlaf134"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30796-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00877-21"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/10600280221085551"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12030516"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00665-23"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa370"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06799-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06873-0"},{"key":"e_1_3_4_12_2","volume-title":"Clinical 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Performance standards for antimicrobial susceptibility testing. In Clinical and laboratory standards institute M100TM, 35th ed","edition":"35"},{"key":"e_1_3_4_13_2","unstructured":"Testing ECoAS. 2024. Guidance document on broth microdilution testing of cefiderocol. Available from: https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Guidance_documents\/Cefiderocol_MIC_testing_EUCAST_guidance_document_January_2024.pdf"},{"key":"e_1_3_4_14_2","unstructured":"EUCAST. 2024. EUCAST reading guide for broth microdilution. Version 50"},{"key":"e_1_3_4_15_2","unstructured":"Testing ECoAS. 2025. Version 13.0. EUCAST disk diffusion method for antimicrobial susceptibility testing. EUCAST V\u00e4xj\u00f6 Sweden. Available from: https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Disk_test_documents\/2025_manuals\/Manual_v_13.0_EUCAST_Disk_Test_2025.pdf"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000004588"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12071212"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179228"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91456-0"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01083-19"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2022.05.011"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13464"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02388-8"},{"key":"e_1_3_4_24_2","unstructured":"Hawser S. KN Valmont N Louvel S Zampaloni C. 2024. MIC distributions and activity of the novel anti-Acinetobacter agent zosurabalpin (RG6006) Poster presented at ECCMID 2024 April 27-30 2024 in Barcelona Spain"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00727-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00727-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:02:51Z","timestamp":1791378171000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00727-26"}},"subtitle":[],"editor":[{"given":"Alessandra","family":"Carattoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1128\/aac.00727-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00727-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00727-26"}}