{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:04:58Z","timestamp":1790827498579,"version":"4.1.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Evopoint Biosciences USA, Inc","award":["Pulmonary Penetration Study"],"award-info":[{"award-number":["Pulmonary Penetration Study"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Funobactam (formerly XNW4107) is a novel non-\u03b2-lactam diazabicyclooctane \u03b2-lactamase inhibitor with potent direct activity against Ambler classes A, C, and D \u03b2-lactamases. Imipenem in combination with funobactam exhibits robust activity against carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Enterobacterales<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      . This study evaluated the intrapulmonary pharmacokinetics of funobactam, imipenem, and cilastatin in healthy subjects. Twenty participants received a 60 min intravenous infusion of imipenem 500 mg\/cilastatin 500 mg combined with funobactam 250 mg every 6 h for five doses. Bronchoalveolar lavage (BAL) was performed at 1, 2, 4, or 6 h after the fifth dose (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5 per sampling time point) to determine epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations. The means from each plasma sampling time corresponding to the BAL sampling time were used to estimate the area under the curve from 0 to 6 h (AUC\n                      <jats:sub>0\u20136h<\/jats:sub>\n                      ) for plasma, and mean concentrations from BAL sampling times from each cohort were used to estimate AUC\n                      <jats:sub>0\u20136h<\/jats:sub>\n                      for ELF and AM concentrations. Intrapulmonary penetration was assessed using AUC\n                      <jats:sub>0\u20136h<\/jats:sub>\n                      ratios of ELF and AM to unbound plasma. The AUC\n                      <jats:sub>0\u20136h<\/jats:sub>\n                      ratios of ELF to unbound plasma for funobactam, imipenem, and cilastatin were 35.2%, 31.8%, and 23.0%, respectively, and the AUC\n                      <jats:sub>0\u20136h<\/jats:sub>\n                      ratios of AM to unbound plasma were 36.6%, 16.8%, and 17.9%, respectively. Funobactam penetrated ELF and AM and exhibited higher intrapulmonary penetration than imipenem and cilastatin, supporting the clinical evaluation of funobactam in combination with imipenem for the treatment of nosocomial pneumonia.\n                    <\/jats:p>\n                    <jats:p>\n                      This study is registered with ClinicalTrials.gov as\n                      <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04802863\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04802863\">NCT04802863<\/jats:related-object>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00524-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:01:46Z","timestamp":1781524906000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Plasma and intrapulmonary pharmacokinetics of funobactam, a novel diazabicyclooctane \u03b2-lactamase inhibitor, administered in combination with imipenem\/cilastatin in healthy subjects"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-7346","authenticated-orcid":true,"given":"Keith","family":"Rodvold","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02mpq6x41","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Illinois Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gotfried","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048qnxy85","id-type":"ROR","asserted-by":"publisher"}],"name":"Pulmonary Associates, PA","place":["Phoenix, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aramayis","family":"Kocharyan","sequence":"additional","affiliation":[{"name":"Clinartis LLC","place":["Hollywood, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigor","family":"Mamikonyan","sequence":"additional","affiliation":[{"name":"Clinartis LLC","place":["Hollywood, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co., Ltd.","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co., Ltd.","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co., Ltd.","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Xu","sequence":"additional","affiliation":[{"name":"Keystone Boanalytical, LLC","place":["North Wales, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijie","family":"Le","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences Co., Ltd.","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7587-5476","authenticated-orcid":true,"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[{"name":"Evopoint Biosciences USA, Inc.","place":["Massachusetts, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","unstructured":"Global antibiotic resistance surveillance report 2025: WHO global antimicrobial resistance and use surveillance system (glass) - summary. 2025. 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Available from: https:\/\/www.cdc.gov\/antimicrobial-resistance\/media\/pdfs\/2019-ar-threats-report-508.pdf?CDC_AAref_Val=https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00582-2017"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867329666220620165429"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00047-19"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-07"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2024-082681"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205073109"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt178"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0902-x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz530"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.04.002"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2022.07.006"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad242"},{"key":"e_1_3_4_17_2","first-page":"1520","volume-title":"ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases","volume":"1","author":"Li J","year":"2024","unstructured":"Li J, Shi Q, Zhao H, Hackel M, Bradford PA, Le M. 2024. 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ESCMID Global 2024, 34th Congress of the European Society of Clinical Microbiology and Infectious Diseases. , Vol. 1, p 2775CMI Communications, Barcelona, Spain. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2950590924000131."},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.09.019"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01433-10"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107266"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01411-17"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv170"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.27.1.42"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1984.129.6.933"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01061-7"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.823684"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.93.03080886"},{"key":"e_1_3_4_29_2","unstructured":"2018. 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