{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:16:33Z","timestamp":1793654193805,"version":"4.5.1"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      BRII-693 is a next-generation synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This study evaluated the pharmacodynamic activity of BRII-693 against common gram-negative pathogens using neutropenic mouse thigh (11 strains) and lung (15 strains) infection models. BRII-693 exhibited dose-dependent increases in pharmacokinetic exposure in both plasma and epithelial lining fluid (ELF). Due to its prolonged elimination half-life within ELF, the ELF area under the curve (AUC) was higher than plasma AUC on a mg\/kg basis. In dose-ranging PK\/PD studies, BRII-693 demonstrated dose-dependent antibacterial activity. In both the thigh and lung models, bacterial stasis was achieved at 24 h plasma AUC\/MIC values of 1\u201319 for\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      , and 1-log kill required only modestly higher targets given the steep exposure-response relationships. Higher target exposures were noted for\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      studies. In the lung model, BRII-693 achieved robust cidal endpoints against all tested organisms. Maximal effect (3\u20134 log reduction in bacterial burden) converged at a 24 h plasma AUC\/MIC value of 50. These findings demonstrate robust PK\/PD profile and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy of BRII-693 against clinically relevant gram-negative pathogens, supporting its potential as a next-generation macrocyclic peptide antibiotic.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01880-25","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:41:48Z","timestamp":1772116908000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacodynamic evaluation of BRII-693, a next-generation synthetic macrocyclic peptide antibiotic, in the neutropenic mouse thigh and lung infection models against gram-negative pathogens"],"prefix":"10.1128","volume":"70","author":[{"given":"Alexander J.","family":"Lepak","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhu","sequence":"additional","affiliation":[{"name":"Brii Biosciences Department of Clinical Pharmacology, Brii Biosciences","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":true,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]},{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology and Immunology, University of Wisconsin","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"CDC. 2022. The biggest antibiotic-resistant threats in the U.S. Centers for Disease Control and Prevention. Available from: https:\/\/www.cdc.gov\/drugresistance\/biggest-threats.html. Retrieved 17 Feb 2023."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2025.06.016"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2025.07.011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14050528"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae332"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00648-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14070703"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab026"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.12.009"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29234-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01497"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.09.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2198"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00903-09"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv267"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01114-09"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq226"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw057"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx409"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01517-20"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3624-3630.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2209"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03572-14"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01452-22"},{"key":"e_1_3_2_27_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically","author":"Clinical and Laboratory Standards Institute","year":"2024","unstructured":"Clinical and Laboratory Standards Institute. 2024 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 12th ed. 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