{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:09Z","timestamp":1791414129122,"version":"4.3.3"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSO100201600002C"],"award-info":[{"award-number":["HHSO100201600002C"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009930","name":"Basilea Pharmaceutica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Francisella tularensis<\/jats:italic>\n                      is the etiologic agent of tularemia, and there are few FDA-approved antibiotics to treat infections. Ceftobiprole medocaril has potential for being developed as a therapeutic for the treatment of inhalational tularemia, as it has previously demonstrated efficacy\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Pharmacokinetic modeling of ceftobiprole in cynomolgus macaques was used to predict an efficacious dose of ceftobiprole medocaril against inhalational tularemia in the disease model based on the measured exposures and human clinical exposure data. The efficacy of ceftobiprole medocaril against inhalational tularemia was then evaluated in the cynomolgus macaque disease model using three doses designed to mimic the human mean clinical exposure of ceftobiprole medocaril (including the predicted efficacious dose). Treatments of 0.00 (placebo), 1.33, 6.67, or 20.0 mg\/kg ceftobiprole medocaril (q8h for 10 days) were administered to cynomolgus macaques by intravenous infusion after animals were exposed to aerosolized\n                      <jats:italic toggle=\"yes\">F. tularensis<\/jats:italic>\n                      and exhibited a fever. Control animals exhibited a 12.5% survival rate, a median time to death of 11.63 days post-challenge, and significantly elevated tissue burdens. By comparison, animals receiving 1.33 mg\/kg treatments with ceftobiprole medocaril exhibited a 50% survival rate, and animals receiving either of the higher doses exhibited an 87.5% survival rate. Evidence of adaptive immunity (seroconversion) was identified in all surviving animals, though detection of\n                      <jats:italic toggle=\"yes\">F. tularensis<\/jats:italic>\n                      with sensitivity to ceftobiprole\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      in a limited number of treated and surviving animals indicates that the clinical efficacy of ceftobiprole medocaril may be enhanced by treatment durations greater than 10 days.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01278-25","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T13:00:36Z","timestamp":1763470836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic modeling and efficacy of ceftobiprole medocaril against pneumonic tularemia in cynomolgus macaques"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4955-7497","authenticated-orcid":true,"given":"Mark M.","family":"Hahn","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-6344","authenticated-orcid":true,"given":"Michael S.","family":"Anderson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0881-8507","authenticated-orcid":true,"given":"Matthew","family":"Snyder","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wantong","family":"Du","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Liang","family":"Chou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"McCracken","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4310-6599","authenticated-orcid":true,"given":"Jennifer I.","family":"Smart","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8243-0482","authenticated-orcid":true,"given":"Karine","family":"Litherland","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Keech","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"von Siebenthal","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Jones","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa N.","family":"Henning","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01h5tnr73","id-type":"ROR","asserted-by":"publisher"}],"name":"Battelle","place":["West Jefferson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.4.631-646.2002"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2763"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.56.012302.160616"},{"key":"e_1_3_4_5_2","volume-title":"Bad bugs, no drugs: as antibiotic discovery stagnates a public health crisis brews","year":"2004","unstructured":"2004. Bad bugs, no drugs: as antibiotic discovery stagnates a public health crisis brews. Infectious Diseases Society of America; Alexandria, VA (2004)."},{"key":"e_1_3_4_6_2","unstructured":"World Health Organization. 2007. WHO guidelines on tularaemia: epidemic and pandemic alert and response. World Health Organization"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00040"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2008.02.008"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.825-836.2001"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkf249"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2007.02.010"},{"key":"e_1_3_4_12_2","unstructured":"U.S. Food and Drug Administration. 2024. FDA approves new antibiotic for three different uses. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-antibiotic-three-different-uses."},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu219"},{"key":"e_1_3_4_14_2","unstructured":"Basilea Pharmaceutica Clinical Trial. 2012. ClinicalTrials.gov identifiers NCT00210964 and NCT00229008. Ceftobiprole in hospital acquired pneumonia"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/507632"},{"key":"e_1_3_4_16_2","unstructured":"Basilea Pharmaceutica Clinical Trial. 2012. ClinicalTrials.Gov Identifier NCT00326287. Ceftobiprole in the treatment of patients with community-acquired pneumonia"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.09.021"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12081337"},{"key":"e_1_3_4_19_2","unstructured":"U.S. Food and Drug Administration. 2002. 21 CFR 314.600-650. 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