{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:36:19Z","timestamp":1776839779379,"version":"3.51.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Burkholderia mallei<\/jats:italic>, the causative agent of glanders, is principally a disease of equines, although it can also infect humans and is categorized by the U.S. Centers for Disease Control and Prevention as a category B biological agent. Human cases of glanders are rare and thus there is limited information on treatment. It is therefore recommended that cases are treated with the same therapies as used for melioidosis, which for prophylaxis, is co-trimoxazole (trimethoprim\/sulfamethoxazole) or co-amoxiclav (amoxicillin\/clavulanic acid). In this study, the fluoroquinolone finafloxacin was compared to co-trimoxazole as a post-exposure prophylactic in a murine model of inhalational glanders. BALB\/c mice were exposed to an aerosol of <jats:italic>B. mallei<\/jats:italic> followed by treatment with co-trimoxazole or finafloxacin initiated at 24 h post-challenge and continued for 14 days. Survival at the end of the study was 55% or 70% for mice treated with finafloxacin or co-trimoxazole, respectively, however, this difference was not significant. However, finafloxacin was more effective than co-trimoxazole in controlling bacterial load within tissues and demonstrating clearance in the liver, lung and spleen following 14 days of therapy. In summary, finafloxacin should be considered as a promising alternative treatment following exposure to <jats:italic>B. mallei.<\/jats:italic><\/jats:p>","DOI":"10.3389\/fmicb.2022.1057202","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T09:09:00Z","timestamp":1669280940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of finafloxacin in a murine model of inhalational glanders"],"prefix":"10.3389","volume":"13","author":[{"given":"Kay B.","family":"Barnes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Bayliss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carwyn","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark I.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Laws","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Vente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah V.","family":"Harding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02110-21","article-title":"Generation of distinct differentially culturable forms of burkholderia following starvation at low temperature.","volume":"10","author":"Auty","year":"2022","journal-title":"Microbiol Spectr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e82","DOI":"10.1128\/AAC.00082-17","article-title":"Demonstrating the Protective Efficacy of the Novel Fluoroquinolone Finafloxacin against an Inhalational Exposure to Burkholderia pseudomallei.","volume":"61","author":"Barnes","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.934312","article-title":"Investigation of a combination therapy approach for the treatment of melioidosis.","volume":"13","author":"Barnes","year":"2022","journal-title":"Front. Microbiol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"e2294","DOI":"10.1128\/AAC.02294-20","article-title":"finafloxacin is an effective treatment for inhalational tularemia and plague in mouse models of infection.","volume":"65","author":"Barnes","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1470","DOI":"10.1128\/AAC.01470-19","article-title":"Demonstration of the broad spectrum in vitro activity of finafloxacin against pathogens of biodefence interest.","volume":"63","author":"Barnes","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1517\/13543784.2015.1052401","article-title":"Finafloxacin for the treatment of urinary tract infections.","volume":"24","author":"Bartoletti","year":"2015","journal-title":"Exp. Opin. Investig. Drugs"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0265023","article-title":"Antibiotics cause metabolic changes in mice primarily through microbiome modulation rather than behavioral changes.","volume":"17","author":"Bongers","year":"2022","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000057839","article-title":"Comparison of side effects of levofloxacin versus other fluoroquinolones.","author":"Carbon","year":"2001","journal-title":"Chemotherapy"},{"key":"B9","first-page":"1","article-title":"Biological and chemical terrorism:strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup.","volume":"49","year":"2000","journal-title":"MMWR Recommend Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.cmi.2019.07.028","article-title":"Influence of pH on the activity of finafloxacin against extracellular and intracellular Burkholderia thailandensis, Yersinia pseudotuberculosis and Francisella philomiragia and on its cellular pharmacokinetics in THP-1 monocytes.","volume":"26","author":"Chalhoub","year":"2020","journal-title":"Clin. Microbiol. Infect"},{"key":"B11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1093\/ije\/dyi271","article-title":"Extreme weather events and environmental contamination are associated with case-clusters of melioidosis in the Northern Territory of Australia.","volume":"35","author":"Cheng","year":"2006","journal-title":"Int. J. Epidemiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/S0140-6736(13)61951-0","article-title":"Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): A multicentre, double-blind, non-inferiority, randomised controlled trial.","volume":"383","author":"Chetchotisakd","year":"2014","journal-title":"Lancet"},{"key":"B13","year":"2006","journal-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard seventh edition: Approved standard M7-A7."},{"key":"B14","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/s0035-9203(00)90333-x","article-title":"Melioidosis: Acute and chronic disease, relapse and re-activation.","volume":"94","author":"Currie","year":"2000","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1128\/AAC.00886-10","article-title":"Comparative in vitro activities of the novel antibacterial finafloxacin against selected Gram-positive and Gram-negative bacteria tested in Mueller-Hinton broth and synthetic urine.","volume":"55","author":"Dalhoff","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ijantimicag.2014.01.005","article-title":"Treatment and prophylaxis of melioidosis.","volume":"43","author":"Dance","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B17","doi-asserted-by":"crossref","first-page":"570","DOI":"10.2460\/javma.233.4.570","article-title":"Glanders.","volume":"233","author":"Dvorak","year":"2008","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1093\/jac\/dkq375","article-title":"Antibacterial activity of finafloxacin under different pH conditions against isogenic strains of Escherichia coli expressing combinations of defined mechanisms of fluoroquinolone resistance.","volume":"65","author":"Emrich","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1586\/eri.10.4","article-title":"Present and future therapeutic strategies for melioidosis and glanders.","volume":"8","author":"Estes","year":"2010","journal-title":"Exp. Rev. Anti. Infect Ther."},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-86054-z","article-title":"Detection of differentially culturable tubercle bacteria in sputum using mycobacterial culture filtrates.","volume":"11","author":"Gordhan","year":"2021","journal-title":"Sci. Rep."},{"key":"B21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1152\/ajplegacy.1947.150.1.70","article-title":"Measurement of the respiratory volumes of laboratory animals.","volume":"150","author":"Guyton","year":"1947","journal-title":"Am. J. Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1017\/s0022172400015801","article-title":"The respiratory retention of bacterial aerosols: Experiments with radioactive spores.","volume":"51","author":"Harper","year":"1953","journal-title":"J. Hyg (Lond)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.vascn.2003.07.001","article-title":"The automated bioaerosol exposure system: Preclinical platform development and a respiratory dosimetry application with nonhuman primates.","volume":"49","author":"Hartings","year":"2004","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.760698","article-title":"finafloxacin, a novel fluoroquinolone, reduces the clinical signs of infection and pathology in a mouse model of Q fever.","volume":"12","author":"Hartley","year":"2021","journal-title":"Front. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev.micro.55.1.235","article-title":"Biological weapons\u2013a primer for microbiologists.","volume":"55","author":"Hawley","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"key":"B26","year":"2008","journal-title":"Guidelines for action in the event of a deliberate release: Glanders and melioidosis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1128\/AAC.45.7.2119-2121.2001","article-title":"In vitro antibiotic susceptibilities of Burkholderia mallei (causative agent of glanders) determined by broth microdilution and E-test.","volume":"45","author":"Heine","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1128\/AAC.01637-09","article-title":"Activity of the investigational fluoroquinolone finafloxacin against ciprofloxacin-sensitive and -resistant Acinetobacter baumannii isolates.","volume":"54","author":"Higgins","year":"2010","journal-title":"Antimicrob. Agents Chemother"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-88","article-title":"Comparison of the in vitro and in vivo susceptibilities of Burkholderia mallei to Ceftazidime and Levofloxacin.","volume":"9","author":"Judy","year":"2009","journal-title":"BMC Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1128\/AAC.43.11.2773","article-title":"In vitro susceptibilities of Burkholderia mallei in comparison to those of other pathogenic Burkholderia spp.","volume":"43","author":"Kenny","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ijantimicag.2011.03.002","article-title":"Activity of finafloxacin, a novel fluoroquinolone with increased activity at acid pH, towards extracellular and intracellular Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila.","volume":"38","author":"Lemaire","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B32","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1007\/s40265-015-0384-z","article-title":"Finafloxacin: First global approval.","volume":"75","author":"McKeage","year":"2015","journal-title":"Drugs"},{"key":"B33","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1080\/09168451.2019.1676696","article-title":"Antibiotics can cause weight loss by impairing gut microbiota in mice and the potent benefits of lactobacilli.","volume":"84","author":"Miao","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1111\/iep.12105","article-title":"Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus).","volume":"95","author":"Nelson","year":"2014","journal-title":"Int. J. Exp. Pathol."},{"key":"B35","article-title":"Glanders and melioidosis","author":"Nguyen","year":"2022","journal-title":"StatPearls"},{"key":"B36","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1056\/NEJM200107263450404","article-title":"Glanders in a military research microbiologist.","volume":"345","author":"Srinivasan","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4394","DOI":"10.1128\/AAC.00833-10","article-title":"In vitro spectrum of activity of finafloxacin, a novel, pH-activated fluoroquinolone, under standard and acidic conditions.","volume":"55","author":"Stubbings","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B38","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/jac\/dkh471","article-title":"Antibiotic susceptibility of 65 isolates of Burkholderia pseudomallei and Burkholderia mallei to 35 antimicrobial agents.","volume":"54","author":"Thibault","year":"2004","journal-title":"J Antimicrob Chemother"},{"key":"B39","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1016\/j.vaccine.2017.03.022","article-title":"Burkholderia pseudomallei and Burkholderia mallei vaccines: Are we close to clinical trials?","volume":"35","author":"Titball","year":"2017","journal-title":"Vaccine"},{"key":"B40","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-8-131","article-title":"Glanders: An overview of infection in humans.","volume":"8","author":"Van Zandt","year":"2013","journal-title":"Orphanet. J. Rare Dis."},{"key":"B41","article-title":"Rapid activity of finafloxacin in patients with urinary tract infections and pyelonephritis evaluated in phase 2 clinical studies.","volume":"171","author":"Vente","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1128\/AAC.04801-14","article-title":"Efficacy of postexposure therapy against glanders in mice.","volume":"59","author":"Waag","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B43","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/j.1574-6968.2007.00949.x","article-title":"Glanders: Off to the races with Burkholderia mallei.","volume":"277","author":"Whitlock","year":"2007","journal-title":"FEMS Microbiol. Lett."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1057202\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T09:09:08Z","timestamp":1669280948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1057202\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":43,"alternative-id":["10.3389\/fmicb.2022.1057202"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.1057202","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]},"article-number":"1057202"}}