{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:19:00Z","timestamp":1753881540416,"version":"3.41.2"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"HHS | U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["U18-FD004004"],"award-info":[{"award-number":["U18-FD004004"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HHS | National Institutes of Health","award":["R01-AI111992"],"award-info":[{"award-number":["R01-AI111992"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            More-permissive preclinical models may be useful in evaluating antituberculosis regimens for their propensity to select drug-resistant mutants. To evaluate whether acquired rifamycin monoresistance could be recapitulated in mice and, if so, to evaluate the effects of immunodeficiency, intermittent dosing, and drug exposures, athymic nude and BALB\/c mice were infected. Controls received daily rifapentine alone or 2 months of rifampin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampin\/isoniazid, either daily or twice weekly with one of two isoniazid doses. Test groups received the same intensive regimen followed by once-weekly rifapentine or isoniazid\/rifapentine with rifapentine doses of 10, 15, or 20 mg\/kg of body weight plus one of two isoniazid doses. All combination regimens rendered BALB\/c mouse cultures negative but selected mutants resistant to isoniazid (8.5%, 12\/140) or rifampin (3.5%, 5\/140) in nude mice (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). Intermittently dosed intensive-phase therapy selected isoniazid and rifampin resistance in 10% (8\/80,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001) and 20% (16\/80,\n            <jats:italic>P<\/jats:italic>\n            = 0.009) of nude mice, respectively, compared to 0% treated with a daily regimen. Once-weekly rifapentine-containing continuation-phase regimens selected rifampin-resistant mutants at a rate of 18.0% (18\/100,\n            <jats:italic>P<\/jats:italic>\n            = 0.035 compared to rifampin\/isoniazid regimens). Higher isoniazid doses in the intermittent-treatment control regimen and higher rifapentine doses in once-weekly regimens were associated with less selection of isoniazid resistance. Acquired resistance, including rifamycin monoresistance, was more likely to occur in nude mice despite administration of combination therapy. These results recapitulate clinical outcomes and indicate that nude mice may be useful for evaluating the ability of novel regimens to prevent the selection of resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.01502-17","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:30:20Z","timestamp":1504657820000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Immunodeficiency and Intermittent Dosing Promote Acquired Rifamycin Monoresistance in Murine Tuberculosis"],"prefix":"10.1128","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-1897","authenticated-orcid":false,"given":"Sang-Won","family":"Park","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Seoul National University College of Medicine and Boramae Medical Center, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rokeya","family":"Tasneen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Converse","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric L.","family":"Nuermberger","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"issue":"11","key":"e_1_3_2_2_2","first-page":"1","article-title":"Treatment of tuberculosis","volume":"52","author":"American Thoracic Society; CDC; Infectious Diseases Society of America","year":"2003","unstructured":"American Thoracic Society; CDC; Infectious Diseases Society of America. 2003. Treatment of tuberculosis. MMWR Recomm Rep52(RR-11):1\u201377.","journal-title":"MMWR Recomm Rep"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11467-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200503-417OC"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663785"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)03027-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/516146"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.2.9805097"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/430377"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/381675"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201012-1949OC"},{"key":"e_1_3_2_12_2","unstructured":"Park\nSW\nNuermbergerEL. 2012. Recapitulation of acquired rifamycin mono-resistance in an immunosuppressed mouse model of TB. Abstr Conf Retroviruses Opportunistic Infect (CROI) abstr 936."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu674"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw376"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200407-905OC"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2409005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200208-951OC"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit352"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/429321"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00691-14"},{"key":"e_1_3_2_21_2","first-page":"1320","article-title":"Mechanisms of drug resistance in Mycobacterium tuberculosis","volume":"13","author":"Zhang Y","year":"2009","unstructured":"Zhang Y YewWW. 2009. Mechanisms of drug resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis13:1320\u20131330.","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1054\/tuld.1998.0002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00830-09"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/510247"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.4955-4960.2002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.9.3373-3381.2004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/651686"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00912-12"},{"key":"e_1_3_2_29_2","first-page":"565","article-title":"Mycobacteria: laboratory methods for testing drug sensitivity and resistance","volume":"29","author":"Canetti G","year":"1963","unstructured":"Canetti G FromanSGrossetJHauduroyPLangerovaMMahlerHTMeissnerGMitchisonDASulaL. 1963. 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