{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:32:35Z","timestamp":1779114755095,"version":"3.51.4"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201000003I"],"award-info":[{"award-number":["HHSN272201000003I"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN27200009"],"award-info":[{"award-number":["HHSN27200009"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201000017I"],"award-info":[{"award-number":["HHSN272201000017I"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN27200005"],"award-info":[{"award-number":["HHSN27200005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ciprofloxacin and levofloxacin, 2 fluoroquinolone antimicrobials, are \u226590% effective for the treatment of inhalational plague when administered within 2\u20136 hours of fever onset in African green monkeys (AGM). Based on data in the AGM model, these antimicrobials were approved under the Food and Drug Administration\u2019s Animal Efficacy Rule. However, that data did not address the issue of how long treatment with these antimicrobials would remain effective after fever onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The AGM model of pneumonic plague was used to explore the effect of delaying treatment with ciprofloxacin and levofloxacin on efficacy. In 2 studies, AGMs were challenged with inhaled lethal doses of Yersinia pestis. Treatment with ciprofloxacin and levofloxacin was initiated from 0 to up to 30 hours after fever onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Challenged animals all developed fever within 78 hours and were treated with ciprofloxacin (n\u2005=\u200527) or levofloxacin (n\u2005=\u200529) at various predetermined time points postfever. When administered 10 hours after fever onset, 10 days of ciprofloxacin and levofloxacin treatment remained very effective (90 or 100%, respectively). The efficacy of both antimicrobials declined as treatment initiation was further delayed. Statistical analyses estimated the treatment delay times at which half of the AGMs were no longer expected to survive as 19.7 hours for ciprofloxacin and 26.5 hours for levofloxacin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that there is a narrow window following fever onset during which ciprofloxacin and levofloxacin are fully effective treatment options for pneumonic plague in AGMs. Since the timing of disease is similar in humans and AGMs, these AGM data are reasonably likely to predict response times for treatment in humans.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz1234","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T20:19:43Z","timestamp":1578082783000},"page":"S60-S65","source":"Crossref","is-referenced-by-count":8,"title":["Effect of Delaying Treatment on Efficacy of Ciprofloxacin and Levofloxacin in the African Green Monkey Model of Pneumonic Plague"],"prefix":"10.1093","volume":"70","author":[{"given":"Joseph L","family":"Campbell","sequence":"first","affiliation":[{"name":"Office of Biodefense, Research Resources and Translational Research, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P","family":"Fay","sequence":"first","affiliation":[{"name":"Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynda L","family":"Lanning","sequence":"first","affiliation":[{"name":"Office of Regulatory Affairs, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-7437","authenticated-orcid":false,"given":"Judith A","family":"Hewitt","sequence":"first","affiliation":[{"name":"Office of Biodefense, Research Resources and Translational Research, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"2020052103181729100_CIT0001","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1128\/CMR.10.1.35","article-title":"Yersinia pestis\u2013etiologic agent of plague","volume":"10","author":"Perry","year":"1997","journal-title":"Clin Microbiol Rev"},{"key":"2020052103181729100_CIT0002","doi-asserted-by":"crossref","article-title":"The African green monkey model of pneumonic plague and US Food and Drug Administration approval of antimicrobials under the animal rule","author":"Hewitt","DOI":"10.1093\/cid\/ciz1233"},{"key":"2020052103181729100_CIT0003","doi-asserted-by":"crossref","first-page":"e959","DOI":"10.1371\/journal.pntd.0000959","article-title":"Levofloxacin cures experimental pneumonic plague in African green monkeys","volume":"5","author":"Layton","year":"2011","journal-title":"PLOS Negl Trop Dis"},{"key":"2020052103181729100_CIT0004","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4269\/ajtmh.1994.51.109","article-title":"Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona","volume":"51","author":"Doll","year":"1994","journal-title":"Am J Trop Med Hyg"},{"key":"2020052103181729100_CIT0005","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1179\/joc.1997.9.6.391","article-title":"Streptococcus pneumoniae killing rate and post-antibiotic effect of levofloxacin and ciprofloxacin","volume":"9","author":"Fuchs","year":"1997","journal-title":"J Chemother"},{"key":"2020052103181729100_CIT0006","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/jac\/dkg380","article-title":"Comparative antimicrobial activity of levofloxacin and ciprofloxacin against Streptococcus 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