{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:05:43Z","timestamp":1773756343886,"version":"3.50.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2001,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rifalazil, also known as KRM-1648 or benzoxazinorifamycin, is a new semisynthetic rifamycin with a long half-life of approximately 60 h. Rifalazil has potent bactericidal activity against\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            in vitro and in animal models of tuberculosis (TB). Prior studies in healthy volunteers showed that once-weekly doses of 25 to 50 mg of rifalazil were well tolerated. In this randomized, open-label, active-controlled phase II clinical trial, 65 subjects with sputum smear-positive pulmonary TB received one of the following regimens for the first 2 weeks of therapy: 16 subjects received isoniazid (INH) (5 mg\/kg of body weight) daily; 16 received INH (5 mg\/kg) and rifampin (10 mg\/kg) daily; 17 received INH (5 mg\/kg) daily plus 10 mg of rifalazil once weekly; and 16 received INH (5 mg\/kg) daily and 25 mg of rifalazil once weekly. All subjects were then put on 6 months of standard TB therapy. Pretreatment and day 15 sputum CFU of\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            were measured to assess the bactericidal activity of each regimen. The number of drug-related adverse experiences was low and not significantly different among treatment arms. A transient decrease in absolute neutrophil count to less than 2,000 cells\/mm\n            <jats:sup>3<\/jats:sup>\n            was detected in 10 to 20% of patients in the rifalazil- and rifampin-containing treatment arms without clinical consequences. Decreases in CFU counts were comparable among the four treatment arms; however, the CFU results were statistically inconclusive due to the variability in the control arms. Acquired drug resistance did not occur in any patient. Studies focused on determining a maximum tolerated dose will help elucidate the full anti-TB effect of rifalazil.\n          <\/jats:p>","DOI":"10.1128\/aac.45.7.1972-1976.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:30Z","timestamp":1027763730000},"page":"1972-1976","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Safety and Bactericidal Activity of Rifalazil in Patients with Pulmonary Tuberculosis"],"prefix":"10.1128","volume":"45","author":[{"given":"Reynaldo","family":"Dietze","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Nu\u0301cleo de Doenc\u0327as Infecciosas Centro Biome\u0301dico, Universidade Federal de Esp\u0131\u0301rito Santo, Vito\u0301ria, Brazil1;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucile\u0301ia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Nu\u0301cleo de Doenc\u0327as Infecciosas Centro Biome\u0301dico, Universidade Federal de Esp\u0131\u0301rito Santo, Vito\u0301ria, Brazil1;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia Ma\u0301rcia Canedo","family":"Rocha","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Nu\u0301cleo de Doenc\u0327as Infecciosas Centro Biome\u0301dico, Universidade Federal de Esp\u0131\u0301rito Santo, Vito\u0301ria, Brazil1;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moise\u0301s","family":"Palaci","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Nu\u0301cleo de Doenc\u0327as Infecciosas Centro Biome\u0301dico, Universidade Federal de Esp\u0131\u0301rito Santo, Vito\u0301ria, Brazil1;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Infectious Diseases, Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio2;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Wells","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->PathoGenesis Corporation, Seattle, Washington3; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Rose","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->PathoGenesis Corporation, Seattle, Washington3; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Eisenach","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->University of Arkansas for Medical Sciences, Little Rock, Arkansas4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrold J.","family":"Ellner","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Infectious Diseases, Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio2;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.2165\/00003495-197509050-00003","article-title":"Drug treatment of pulmonary tuberculosis.","volume":"9","author":"Aquinas M.","year":"1975","unstructured":"Aquinas M. Drug treatment of pulmonary tuberculosis. Drugs 9 1975 364 372","journal-title":"Drugs"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0140-6736(96)90537-1","article-title":"Results of directly observed short-course chemotherapy in 112,842 Chinese patients with smear positive tuberculosis.","volume":"347","author":"China Tuberculosis Control Collaboration","year":"1996","unstructured":"China Tuberculosis Control Collaboration Results of directly observed short-course chemotherapy in 112,842 Chinese patients with smear positive tuberculosis. Lancet 347 1996 358 362","journal-title":"Lancet"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.1.9811006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1093\/clinids\/21.3.594","article-title":"Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease.","volume":"21","author":"Griffith D. E.","year":"1995","unstructured":"Griffith D. E. Brown B. A. Girard W. M. Wallace R. J. Jr. Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Clin. Infect. Dis. 21 1995 594 598","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.10.2295"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2749"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0378-4274(97)00098-2","article-title":"HIV protease inhibitors, saquinavir, indinavir and ritonavir: inhibition of CYP3A4-mediated metabolism of testosterone and benzoxazinorifamycin, KRM-1648, in human liver microsomes.","volume":"93","author":"Inaba T.","year":"1997","unstructured":"Inaba T. Fischer N. E. Riddick D. S. Stewart D. J. Hidaka T. HIV protease inhibitors, saquinavir, indinavir and ritonavir: inhibition of CYP3A4-mediated metabolism of testosterone and benzoxazinorifamycin, KRM-1648, in human liver microsomes. Toxicol. Lett. 93 1997 215 219","journal-title":"Toxicol. Lett."},{"key":"e_1_3_2_9_2","first-page":"939","article-title":"The early bactericidal activity of drugs in patients with pulmonary tuberculosis.","volume":"121","author":"Jindani A.","year":"1980","unstructured":"Jindani A. Aber V. R. Edwards E. A. Mitchison D. A. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am. Rev. Respir. Dis. 121 1980 939 949","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_10_2","unstructured":"Kent\n              P. T.\n              Kubica\n              G. P\n          Public health mycobacteriology\u2014a guide for the level III laboratory. Centers for Disease Control publication PB 86-216546.\n          1985\n          Centers for Disease Control\n          Atlanta Ga"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.298"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1080\/004982598239173","article-title":"Effect of a new rifamycin derivative, rifalazil, on liver microssomal enzyme induction in rat and dog.","volume":"28","author":"Mae T.","year":"1998","unstructured":"Mae T. Hosoe K. Fujii K. Yamamoto T. Hidaka T. Ohashi T. Kleeman J. M. Adams P. E. Effect of a new rifamycin derivative, rifalazil, on liver microssomal enzyme induction in rat and dog. Xenobiotica 28 1998 759 766","journal-title":"Xenobiotica"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1164\/ajrccm.154.4.8887600","article-title":"Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis.","volume":"154","author":"Moore R. D.","year":"1996","unstructured":"Moore R. D. Chaulk C. P. Griffiths R. Cavalcante S. Chaisson R. E. Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis. Am. J. Respir. Crit. Care Med. 154 1996 1013 1019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.115.1.12"},{"key":"e_1_3_2_15_2","first-page":"A495","article-title":"Safety and pharmacokinetics of PA-1648 a new rifamycin in normal volunteers.","volume":"159","author":"Rose L. M.","year":"1999","unstructured":"Rose L. M. Vasiljev-K M. Adams P. Mizuno V. Wells C. Montgomery A. B. Safety and pharmacokinetics of PA-1648 a new rifamycin in normal volunteers. Am. J. Respir. Crit. Care Med. 159 (Suppl.) 1999 A495","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"e_1_3_2_16_2","first-page":"634","article-title":"Rapid radiometric tests to detect and differentiate Mycobacterium tuberculosis and Mycobacterium bovis from other mycobacterial species.","volume":"130","author":"Siddiqi S. H.","year":"1984","unstructured":"Siddiqi S. H. Hwangbo C. C. Silcox V. Goud R. C. Snider D. E. Middlebrook G. Rapid radiometric tests to detect and differentiate Mycobacterium tuberculosis and Mycobacterium bovis from other mycobacterial species. Am. Rev. Respir. Dis. 130 1984 634 640","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_17_2","unstructured":"Siddiqi\n              S.\n          Radiometric (BACTEC) tests for slow growing mycobacteria\n          Clinical microbiology procedures handbook.\n              Isenberg\n              H. D.\n          1992\n          5.14.7-5.14.25\n          American Society for Microbiology\n          Washington D.C."},{"key":"e_1_3_2_18_2","first-page":"1105","article-title":"Controlled trial of intermittent regimens of rifampicin plus isoniazid for pulmonary tuberculosis in Singapore.","author":"Singapore Tuberculosis Service","year":"1975","unstructured":"Singapore Tuberculosis Service Controlled trial of intermittent regimens of rifampicin plus isoniazid for pulmonary tuberculosis in Singapore. Lancet ii 1975 1105 1109","journal-title":"Lancet"},{"key":"e_1_3_2_19_2","first-page":"251","article-title":"Leucopenia caused by two rifampicin preparations.","volume":"65","author":"Van Assendelft A. H. W.","year":"1984","unstructured":"Van Assendelft A. H. W. Leucopenia caused by two rifampicin preparations. Eur. J. Respir. Dis. 65 1984 251 258","journal-title":"Eur. J. Respir. Dis."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1086\/515701","article-title":"Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.","volume":"178","author":"Wallis R. S.","year":"1998","unstructured":"Wallis R. S. Perkins M. D. Phillips M. Joloba M. Demchuk B. Namale A. Johnson J. L. Williams D. Wolski K. Teixeira L. Dietze R. Mugerwa R. D. Eisenach K. D. Ellner J. J. Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment. J. Infect. Dis. 178 1998 1115 1121","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.7.1853"},{"key":"e_1_3_2_22_2","unstructured":"World Health Organization\n          Global tuberculosis programme. Global tuberculosis control report WHO\/TB\/99.259.\n          1988\n          World Health Organization\n          Geneva Switzerland"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.7.1944-1947.1995"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.45.7.1972-1976.2001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.45.7.1972-1976.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:16:38Z","timestamp":1645463798000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.45.7.1972-1976.2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2001,7]]}},"alternative-id":["10.1128\/AAC.45.7.1972-1976.2001"],"URL":"https:\/\/doi.org\/10.1128\/aac.45.7.1972-1976.2001","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,7]]},"assertion":[{"value":"2000-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}