This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dietze, R.
Right arrow Articles by Ellner, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dietze, R.
Right arrow Articles by Ellner, J. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2001, p. 1972-1976, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.1972-1976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Safety and Bactericidal Activity of Rifalazil in Patients with Pulmonary Tuberculosis

Reynaldo Dietze,1,* Luciléia Teixeira,1 Lia Márcia Canedo Rocha,1 Moisés Palaci,1 John L. Johnson,2 Charles Wells,3,dagger Lynn Rose,3 Kathleen Eisenach,4 and Jerrold J. Ellner2,Dagger

Núcleo de Doenças Infecciosas Centro Biomédico, Universidade Federal de Espírito Santo, Vitória, Brazil1; Division of Infectious Diseases, Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio2; PathoGenesis Corporation, Seattle, Washington3; and University of Arkansas for Medical Sciences, Little Rock, Arkansas4

Received 11 May 2000/Returned for modification 21 October 2000/Accepted 27 March 2001

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 Mycobacterium tuberculosis 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 M. tuberculosis 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/mm3 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.

* Corresponding author. Mailing address: Núcleo de Doenças Infecciosas, Centro Biomédico, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Vitória, Espírito Santo CEP 29040-091, Brazil. Phone: 55 (27) 335-7204. Fax: 55 (27) 335-7206. E-mail: rdietze{at}npd.ufes.br.

dagger Present address: Division of Tuberculosis Elimination-NCHSTP, Centers for Disease Control and Prevention, Atlanta, GA 30333.

Dagger Present address: New Jersey School of Medicine and Dentistry, Newark, New Jersey.

Antimicrobial Agents and Chemotherapy, July 2001, p. 1972-1976, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.1972-1976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Mdivani, N., Li, H., Akhalaia, M., Gegia, M., Goginashvili, L., Kernodle, D. S., Khechinashvili, G., Tang, Y.-W. (2009). Monitoring Therapeutic Efficacy by Real-Time Detection of Mycobacterium tuberculosis mRNA in Sputum. Clin. Chem. 55: 1694-1700 [Abstract] [Full Text]  
  • Palaci, M., Dietze, R., Hadad, D. J., Ribeiro, F. K. C., Peres, R. L., Vinhas, S. A., Maciel, E. L. N., do Valle Dettoni, V., Horter, L., Boom, W. H., Johnson, J. L., Eisenach, K. D. (2007). Cavitary Disease and Quantitative Sputum Bacillary Load in Cases of Pulmonary Tuberculosis. J. Clin. Microbiol. 45: 4064-4066 [Abstract] [Full Text]  
  • Rothstein, D. M., Farquhar, R. S., Sirokman, K., Sondergaard, K. L., Hazlett, C., Doye, A. A., Gwathmey, J. K., Mullin, S., van Duzer, J., Murphy, C. K. (2006). Efficacy of Novel Rifamycin Derivatives against Rifamycin-Sensitive and -Resistant Staphylococcus aureus Isolates in Murine Models of Infection. Antimicrob. Agents Chemother. 50: 3658-3664 [Abstract] [Full Text]  
  • Murphy, C. K., Mullin, S., Osburne, M. S., van Duzer, J., Siedlecki, J., Yu, X., Kerstein, K., Cynamon, M., Rothstein, D. M. (2006). In Vitro Activity of Novel Rifamycins against Rifamycin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 50: 827-834 [Abstract] [Full Text]  
  • Labro, M. T., Ollivier, V., Babin-Chevaye, C. (2005). Interaction of Rifalazil with Oxidant-Generating Systems of Human Polymorphonuclear Neutrophils. Antimicrob. Agents Chemother. 49: 5018-5023 [Abstract] [Full Text]  
  • Kutlin, A., Kohlhoff, S., Roblin, P., Hammerschlag, M. R., Riska, P. (2005). Emergence of Resistance to Rifampin and Rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis. Antimicrob. Agents Chemother. 49: 903-907 [Abstract] [Full Text]  
  • Suchland, R. J., Bourillon, A., Denamur, E., Stamm, W. E., Rothstein, D. M. (2005). Rifampin-Resistant RNA Polymerase Mutants of Chlamydia trachomatis Remain Susceptible to the Ansamycin Rifalazil. Antimicrob. Agents Chemother. 49: 1120-1126 [Abstract] [Full Text]  
  • Roblin, P. M., Reznik, T., Kutlin, A., Hammerschlag, M. R. (2003). In Vitro Activities of Rifamycin Derivatives ABI-1648 (Rifalazil, KRM-1648), ABI-1657, and ABI-1131 against Chlamydia trachomatis and Recent Clinical Isolates of Chlamydia pneumoniae. Antimicrob. Agents Chemother. 47: 1135-1136 [Abstract] [Full Text]  
  • O'Brien, R. J. (2002). Studies of the Early Bactericidal Activity of New Drugs for Tuberculosis: A Help or a Hindrance to Antituberculosis Drug Development?. Am. J. Respir. Crit. Care Med. 166: 3-4 [Full Text]  
  • Tomioka, H., Sato, K., Sano, C., Sano, K., Shimizu, T. (2002). Intramacrophage Passage of Mycobacterium tuberculosis and M. avium Complex Alters the Drug Susceptibilities of the Organisms as Determined by Intracellular Susceptibility Testing Using Macrophages and Type II Alveolar Epithelial Cells. Antimicrob. Agents Chemother. 46: 519-521 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»