{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:07:54Z","timestamp":1740128874251,"version":"3.37.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"Supplement_3","funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Office of the Assistant Secretary for Preparedness and Response"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sufficient and diverse medical countermeasures against severe pathogenic infections, such as inhalation anthrax, are a critical need. Azithromycin and clarithromycin are antimicrobials commonly used for both upper and lower respiratory infections. They inhibit protein synthesis by blocking the formation of the 50S ribosomal subunit. To expand the armamentarium, these 2 antibiotics were evaluated in a postexposure prophylactic model of inhalation anthrax in cynomolgus macaques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prophylaxis study had 4 test arms: azithromycin, clarithromycin, a levofloxacin control, and a placebo. Beginning 24\u2005hours after exposure to a target challenge dose of 200 lethal dose 50 (LD50) of Bacillus anthracis Ames spores, animals were treated orally until 30 days postchallenge and then observed until 75 days postchallenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The test group that received clarithromycin had a survival rate of 67%. The test group that received azithromycin had a survival rate of 50%, but the peak azithromycin plasma levels achieved were &amp;lt;30\u2005ng\/mL\u2014much lower than the expected 410\u2005ng\/mL. The levofloxacin positive control had a survival rate of 50%; all of the negative controls succumbed to infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The efficacy of clarithromycin prophylaxis was statistically significant compared with placebo, while azithromycin prophylaxis was indistinguishable from placebo. Given the low plasma concentrations of azithromycin achieved in the study, it is not surprising that half the animals succumbed to anthrax during the dosing period; the animals that survived beyond the time during which placebo control animals succumbed survived to the end of the observation period.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciac569","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T18:49:20Z","timestamp":1666032560000},"page":"S411-S416","source":"Crossref","is-referenced-by-count":4,"title":["Determination of the Postexposure Prophylactic Benefit of Oral Azithromycin and Clarithromycin Against Inhalation Anthrax in Cynomolgus Macaques"],"prefix":"10.1093","volume":"75","author":[{"given":"Raymond M","family":"Slay","sequence":"first","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A","family":"Hewitt","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Crumrine","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/48.suppl_2.1","article-title":"Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site","volume":"48","author":"Douthwaite","year":"2001","journal-title":"J Antimicrob Chemother"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.pharmthera.2014.03.003","article-title":"Azithromycin: mechanisms of action and their relevance for clinical applications","volume":"143","author":"Parnham","year":"2014","journal-title":"Pharmacol Ther"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s002849900290","article-title":"Azithromycin and clarithromycin inhibition of 50S ribosomal subunit formation in Staphylococcus aureus cells","volume":"36","author":"Champney","year":"1998","journal-title":"Curr Microbiol"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s002849900402","article-title":"A comparison of the inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells by nine different macrolide antibiotics","volume":"37","author":"Champney","year":"1998","journal-title":"Curr Microbiol"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1097-2765(02)00570-1","article-title":"The structures of four macrolide antibiotics bound to the large ribosomal subunit","volume":"10","author":"Hansen","year":"2002","journal-title":"Mol Cell"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1021\/acs.accounts.1c00020","article-title":"Discovery of macrolide antibiotics effective against multi-drug resistant gram-negative pathogens","volume":"54","author":"Myers","year":"2021","journal-title":"Acc Chem Res"},{"key":"2023030706051015200_","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1128\/AAC.32.5.752","article-title":"In vitro activities of azithromycin (CP 62,993), clarithromycin (A-56268; 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