help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on September 1, 2005, doi:10.1164/rccm.200507-1072OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 11, December 2005, 1457-1462

A more recent version of this article appeared on December 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200507-1072OCv1
172/11/1457    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rosenthal, I. M
Right arrow Articles by Nuermberger, E. L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rosenthal, I. M
Right arrow Articles by Nuermberger, E. L

Submitted on July 12, 2005
Accepted on August 31, 2005

Weekly Moxifloxacin and Rifapentine is More Active than the Denver Regimen in Murine Tuberculosis

Ian M Rosenthal1, Kathy Williams2, Sandeep Tyagi2, Andrew A Vernon3, Charles A Peloquin4, William R Bishai1, Jacques H Grosset2, and Eric L Nuermberger1*

1 Department of Medicine, Johns Hopkins University, Center for Tuberculosis Research, Baltimore, MD, USA; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Department of Medicine, Johns Hopkins University, Center for Tuberculosis Research, Baltimore, MD, USA, 3 Division of Tuberculosis Elimination, Center for Disease Control and Prevention, Atlanta, GA, USA, 4 Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: enuermb{at}jhmi.edu.

Rationale: Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non-high-risk patients. The substitution of moxifloxacin, a new 8- methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens. Methods: In order to test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high risk tuberculosis patients. The bactericidal activity of standard daily therapy and standard intermittent therapy ("Denver" regimen) was also assessed in order to evaluate the effect of intermittent drug administration during the initial phase of therapy. Results: After 2 months of treatment, lung CFU counts were 1 log10 lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen. Conclusions: These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg.
Key words: moxifloxacin, rifapentine, mouse, tuberculosis, intermittent




This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
S. L. Davis, E. L. Nuermberger, P. K. Um, C. Vidal, B. Jedynak, M. G. Pomper, W. R. Bishai, and S. K. Jain
Noninvasive Pulmonary [18F]-2-Fluoro-Deoxy-D-Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment
Antimicrob. Agents Chemother., November 1, 2009; 53(11): 4879 - 4884.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. E. Dorman, J. L. Johnson, S. Goldberg, G. Muzanye, N. Padayatchi, L. Bozeman, C. M. Heilig, J. Bernardo, S. Choudhri, J. H. Grosset, et al.
Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis
Am. J. Respir. Crit. Care Med., August 1, 2009; 180(3): 273 - 280.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. van den Boogaard, G. S. Kibiki, E. R. Kisanga, M. J. Boeree, and R. E. Aarnoutse
New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development
Antimicrob. Agents Chemother., March 1, 2009; 53(3): 849 - 862.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. Veziris, M. Ibrahim, N. Lounis, A. Chauffour, C. Truffot-Pernot, K. Andries, and V. Jarlier
A Once-Weekly R207910-containing Regimen Exceeds Activity of the Standard Daily Regimen in Murine Tuberculosis
Am. J. Respir. Crit. Care Med., January 1, 2009; 179(1): 75 - 79.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
K. Dooley, C. Flexner, J. Hackman, C. A. Peloquin, E. Nuermberger, R. E. Chaisson, and S. E. Dorman
Repeated Administration of High-Dose Intermittent Rifapentine Reduces Rifapentine and Moxifloxacin Plasma Concentrations
Antimicrob. Agents Chemother., November 1, 2008; 52(11): 4037 - 4042.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
I. M. Rosenthal, M. Zhang, D. Almeida, J. H. Grosset, and E. L. Nuermberger
Isoniazid or Moxifloxacin in Rifapentine-based Regimens for Experimental Tuberculosis?
Am. J. Respir. Crit. Care Med., November 1, 2008; 178(9): 989 - 993.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
D. Almeida, E. Nuermberger, S. Tyagi, W. R. Bishai, and J. Grosset
In Vivo Validation of the Mutant Selection Window Hypothesis with Moxifloxacin in a Murine Model of Tuberculosis
Antimicrob. Agents Chemother., December 1, 2007; 51(12): 4261 - 4266.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
G. Tino
Clinical Year in Review IV: Interstitial Lung Disease, Cystic Fibrosis, Pulmonary Infections, and Mycobacterial Disease
Proceedings of the ATS, November 1, 2006; 3(8): 650 - 653.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
I. M. Rosenthal, K. Williams, S. Tyagi, C. A. Peloquin, A. A. Vernon, W. R. Bishai, J. H. Grosset, and E. L. Nuermberger
Potent Twice-Weekly Rifapentine-containing Regimens in Murine Tuberculosis
Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 94 - 101.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. W. Yew and C. C. Leung
Update in tuberculosis 2005.
Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 491 - 498.
[Full Text] [PDF]

Home page
 JWatch Infect. DiseasesHome page
Weekly Combination Therapy for TB?
Journal Watch Infectious Diseases, December 21, 2005; 2005(1221): 7 - 7.
[Full Text]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. A. Nardell and E. J. Rubin
Once upon a Time...: Improved Intermittent Therapy for Tuberculosis--Fact or Fable?
Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1361 - 1362.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. Nuermberger, S. Tyagi, K. N. Williams, I. Rosenthal, W. R. Bishai, and J. H. Grosset
Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model
Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1452 - 1456.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2005 American Thoracic Society 		  New Orleans Int'l Conf