{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:20:02Z","timestamp":1790140802143,"version":"4.0.1"},"reference-count":36,"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"}],"funder":[{"name":"BioVersys AG., Basel, Switzerland"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n BV100 (rifabutin for infusion) is being developed as an intravenous formulation for treating serious or life-threatening infections due to carbapenem-resistant\n Acinetobacter baumannii<\/jats:italic>\n in patients with limited treatment options. Phase 1 studies were conducted to characterize the pharmacokinetics (PK), safety, and tolerability of BV100 in healthy volunteers after single and multiple doses. Single-ascending and multiple-ascending dose studies were conducted in healthy subjects to establish the PK profile of BV100. Blood samples were assayed to determine plasma concentrations of rifabutin and the major metabolite 25-O-desacetyl-rifabutin and to determine PK parameters. Subjects were assessed for safety and tolerability. The PK profile of BV100 was generally dose-proportional in the single-ascending dose studies with a\n t<\/jats:italic>\n 1\/2<\/jats:sub>\n of 7.9\u201356.1 h, and\n T<\/jats:italic>\n max<\/jats:sub>\n of 1.0\u20131.75 h and increasing exposure with dose. A q12h versus q24h dosing interval resulted in approximately a 1.5-fold to 2-fold greater exposure of rifabutin. The 25-O-desacetyl-rifabutin metabolite represented <5% of rifabutin activity. Adverse events were more common at higher doses with q24h versus q12h dosing, and with a 60 min infusion time. The most common adverse events were infusion site events, with systemic treatment-emergent adverse events as expected for the known safety profile of rifabutin. No other treatment-related safety issues were identified. BV100 demonstrated a dose-proportional PK profile and was generally safe and well tolerated. Based on these results, BV100 doses of 200\u2013300 mg q12h are undergoing evaluation in a Phase 2 study for treating carbapenem-resistant\n A. baumannii<\/jats:italic>\n infections.\n <\/jats:p>\n \n CLINICAL TRIALS<\/jats:title>\n \n This study is registered with ClinicalTrials.gov as\n NCT04636983<\/jats:ext-link>\n and\n NCT05087069<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/aac.01582-25","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T15:56:08Z","timestamp":1772466968000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Single-ascending and multiple-ascending dose study of the pharmacokinetics, safety, and tolerability of BV100 (rifabutin for infusion) in healthy volunteers"],"prefix":"10.1128","volume":"70","author":[{"given":"Christian","family":"Kemmer","sequence":"first","affiliation":[{"name":"BioVersys AG","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Nuvisan GmbH","place":["Neu-Ulm, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Reh","sequence":"additional","affiliation":[{"name":"Nuvisan GmbH","place":["Neu-Ulm, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Davila","sequence":"additional","affiliation":[{"name":"TFS","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2731-0327","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Jung","sequence":"additional","affiliation":[{"name":"BioVersys AG","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8791-8923","authenticated-orcid":false,"given":"Lisa","family":"Husband","sequence":"additional","affiliation":[{"name":"TFS","place":["Barcelona, Spain"]},{"name":"BioVersys SAS","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6990-2030","authenticated-orcid":false,"given":"Glenn E.","family":"Dale","sequence":"additional","affiliation":[{"name":"BioVersys AG","place":["Basel, Switzerland"]},{"name":"BioVersys SAS","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"CDC. 2024. Antibiotic resistance threats in the United States 2021-2022. Atlanta GA: U.S Department of Health and Human Services CDC"},{"key":"e_1_3_5_3_2","unstructured":"WHO. 2024. WHO bacterial priority pathogens list 2024: Bacterial pathogens of public health importance to guide research development and strategies to prevent and control antimicrobial resistance"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-16"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9030119"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-015-0077-4"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2019.02.016"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9040205"},{"key":"e_1_3_5_9_2","unstructured":"CDC. 2019. Antibiotic resistance threats in the United States 2019. Atlanta GA: U.S Department of Health and Human Services"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00028-2018"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.09.015"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114515"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2010.02.001"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0737-6"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.8.1237"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa370"},{"key":"e_1_3_5_17_2","unstructured":"Dale G Kemmer C Trebosc V et al.. 2021. In vivo efficacy of BV100 in mouse models of Acinetobacter baumannii infection. ECCMID"},{"key":"e_1_3_5_18_2","unstructured":"Muller AE deWinter BCM Gitzinger M et al.. 2021. Pharmacokinetics and pharmacodynamics of BV100 in neutropenic mouse lung infection models. ECCMID"},{"key":"e_1_3_5_19_2","unstructured":"Pieren M Muller AA Pulse ME et al.. 2024. BV100 displays potent efficacy against Acinetobacter baumannii in neutropaenic murine thigh and lung infection Models. ESCMID"},{"key":"e_1_3_5_20_2","unstructured":"Trebosc V Schellhorn B Schill J et al.. 2021. Rifabutin synergy \/ antagonism with SoC antibiotics in Acinetobacter baumannii. ECCMID"},{"key":"e_1_3_5_21_2","unstructured":"World Health Organization. 2013. Sixty-sixth World Health Assembly Geneva 20\u201327 May 2013. Geneva Switzerland World Health Organization WHA66\/2013\/REC\/1."},{"key":"e_1_3_5_22_2","unstructured":"European Medicines Agency (EMA). 2017. Guideline for good clinical practice E6(R2) (EMA\/CHMP\/ICH\/135\/1995). Available from: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-e-6-r1-guideline-goodclinical-practice-step-5_en.pdf"},{"key":"e_1_3_5_23_2","unstructured":"European Parliament and Council of the European Union. 2001. Directive 2001\/20\/EC"},{"key":"e_1_3_5_24_2","unstructured":"European Commission. 2005. Commission Directive 2005\/28\/EC"},{"key":"e_1_3_5_25_2","unstructured":"Federal Republic of Germany. 2014. Medicinal Products Act in the version published on 12 December 2005 last amended by Article 2a of the Law of 27th March 2014"},{"key":"e_1_3_5_26_2","unstructured":"Federal Republic of Germany. 2004. GCP-Verordnung vom 9. August 2004 (BGBl. I S. 2081) die zuletzt durch Artikel 8 des Gesetzes vom 19. Oktober 2012 (BGBl. I S. 2192) ge\u00e4ndert worden ist"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129804-200611000-00004"},{"key":"e_1_3_5_28_2","unstructured":"European Medicines Agency. 2012. Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.2017"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/22.Supplement_1.S15"},{"key":"e_1_3_5_31_2","unstructured":"Spectrum Safety Data Sheet. 2016. Isosorbide dimethyl ether"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad109"},{"key":"e_1_3_5_33_2","unstructured":"European Centre for Disease Prevention and Control WHO Regional Office for Europe\/ European Centre for Disease Prevention and Control. 2022. Antimicrobial resistance surveillance in Europe 2022\u20132020 data; 2022. Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/antimicrobial-resistance-surveillance-europe-2022-2020-data"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-022-00597-w"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae403"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2209"},{"key":"e_1_3_5_37_2","unstructured":"Ethics Committee of the Bavarian State Chamber of Physicians. 2025 Munich Germany"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01582-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01582-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:01:58Z","timestamp":1775048518000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01582-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"alternative-id":["10.1128\/aac.01582-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01582-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"2025-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01582-25"}}