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Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, December 2001, p. 3482-3486, Vol. 45, No. 12
Laboratoire de Bactériologie,
Faculté de Médecine Pitié-Salpêtrière,
Paris 75634, France1; Division of Tuberculosis
Elimination, Centers for Disease Control and Prevention,
Atlanta, Georgia 303332; and Global
Alliance for TB Drug Development, New York, New York
100383
Received 16 July 2001/Returned for modification 20 August
2001/Accepted 20 September 2001
Mice infected with 1.6 × 107 CFU of
Mycobacterium tuberculosis were treated 14 days later
for 6 months with a regimen of once-weekly 10 mg of rifapentine and 75 mg of isoniazid per kg of body weight supplemented with either 150 mg
of streptomycin per kg or 100 mg of moxifloxacin per kg during either
both the 2-week daily initial and once-weekly continuation phases or
only in the daily 2-week initial phase. On completion of treatment, all
lung cultures were negative, except for three mice, each with a single
colony: two whose rifapentine-isoniazid regimen was supplemented with streptomycin during the whole course of therapy and one whose rifapentine-isoniazid regimen had no initial daily phase, but was
supplemented with streptomycin and moxifloxacin during the whole course
of therapy. After 3 months of follow-up, positive lung cultures were
obtained from 61 and 56% of mice supplemented with streptomycin during
either the full course of therapy or only the daily 2-week initial
phase, respectively, and 15 and 50% of mice supplemented with
moxifloxacin during either the full course of therapy or only the daily
2-week initial phase, respectively. These results suggest that
moxifloxacin has sterilizing activity against M.
tuberculosis.
The operational requirements for the
World Health Organization's directly observed treatment (DOT)
short-course strategy for the control of tuberculosis
(19-21) are difficult to satisfy, particularly in areas
in which the health infrastructure is poor and accessibility of
services is limited. The requirement posing the greatest challenge is
that ingestion of medication actually be observed by a health care
provider, i.e., DOT. If the frequency of drug administration could be
reduced to once weekly while the efficacy of treatment was maintained,
the implementation of DOT would be easier.
Treatment regimens that are based on rifapentine, a drug
recently approved by the U.S. Food and Drug Administration for the treatment of pulmonary tuberculosis (11), offer this
possibility. The pharmacokinetic parameters of rifapentine are very
favorable, because its peak level in serum and half-life are
significantly greater than those of other available rifamycin
derivatives (7). Good bactericidal and sterilizing
activities were observed in mice treated intermittently with 10 mg of
rifapentine per kg of body weight at a frequency of once a week
(2, 7). The addition of 75 mg of isoniazid per kg of body
weight, also given once a week, enhanced the activity of rifapentine in
both immunocompetent (normal) and immunodeficient (nude) mice
(2), suggesting that the combination rifapentine-isoniazid
given once weekly might be an effective intermittent regimen for both
the preventive and curative therapy of tuberculosis.
In another study of mice treated for 8 weeks with various once-weekly
rifapentine-containing drug regimens, a strong bactericidal effect was
consistently observed (5). However the effect was approximately 1 log10 less than that of the
standard daily regimen (i.e., rifampin plus isoniazid plus
pyrazinamide). With an initial 2-week daily supplement of streptomycin,
isoniazid, and pyrazinamide and with the addition of streptomycin to
the once-weekly rifapentine-isoniazid combination, the deficit in
bactericidal effect of the once-weekly rifapentine-isoniazid regimen
was entirely overcome. A subsequent study in mice evaluated various
once-weekly rifapentine-isoniazid-containing regimens with and without
streptomycin given for 8 months (3). That study showed
that 8-month once-weekly rifapentine-isoniazid regimens were successful
only when supplemented with an initial 2-month daily
isoniazid-rifampin-pyrazinamide phase. When the initial daily phase was
reduced to 2 weeks, 8-month, once-weekly regimens containing
rifapentine-isoniazid were successful only if supplemented with
streptomycin during all phases or with daily isoniazid during the
once-weekly phase. This finding was further supported by results of
human clinical trials, in which 6-month regimens with a continuation
phase of once-weekly rifapentine-isoniazid were modestly less effective
than standard twice- or thrice-weekly rifampin-based therapy
(17; Tuberculosis Trial Consortium, submitted for publication).
Of the recently developed fluoroquinolones, moxifloxacin has
demonstrated potent bactericidal activity against Mycobacterium tuberculosis in the mouse model (8, 13), and its long
half-life (16) compared to that of isoniazid, suggests
that it might be a better pharmacokinetic match with rifapentine. The
objective of the present mouse experiment was to determine if
moxifloxacin would increase the bactericidal and sterilizing properties
of once-weekly rifapentine-isoniazid when substituted for streptomycin during both the daily initial and once-weekly continuation phases of
therapy. The efficacy of the regimens was assessed on the basis of
their ability to sterilize lung cultures on completion of the 6-month
therapy, to prevent the selection of drug-resistant organisms, and to
prevent relapse of culture positivity after 3 months of follow-up
without therapy.
Antimicrobial agents.
Rifapentine, rifampin, and
pyrazinamide were kindly provided by Hoechst Marion Roussel
(Romainville, France), and isoniazid was provided by Laphal (Allauch,
France). Streptomycin was purchased from Solvay Pharma (Suresnes,
France), and moxifloxacin was a gift from Bayer (Puteaux, France).
M. tuberculosis strain.
The H37Rv strain of
M. tuberculosis was grown on Löwenstein-Jensen medium.
Colonies were subcultured in Dubos broth (Diagnostics Pasteur, Paris,
France) for 7 days at 37°C. The turbidity of the resulting suspension
was adjusted with normal saline to match that of a standard 1-mg/ml
suspension of Mycobacterium bovis BCG and was further
diluted with normal saline to obtain a 0.2-mg/ml suspension for mouse
inoculation. The MICs of the drugs in micrograms per milliliter for the
H37Rv strain were as follows: rifampin, 0.25; rifapentine, 0.06;
isoniazid, 0.1; streptomycin, 2.0; moxifloxacin, 0.5 on 7H11 agar
medium; and pyrazinamide, 10 on Löwenstein-Jensen medium at pH
5.5.
Infection of mice.
Three hundred eighty female 4-week-old
outbred Swiss mice were purchased from the Janvier Breeding Center (Le
Genest Saint-Isle, France). They were intravenously infected in the
tail vein with 0.5 ml of a bacterial suspension containing
approximately 1.6 × 107 CFU of M. tuberculosis H37Rv.
Chemotherapy.
Following infection, mice were randomly
distributed in three control groups (A to C) and five test groups (D to
H) of 40 to 60 mice each, except for group B, which had 10 mice (Table
1). The first two control groups were
negative controls: group A contained infected and untreated mice to
confirm progressive and fatal tuberculosis infection, and group B
contained mice treated with once-weekly rifapentine alone to ensure
that monotherapy with rifapentine would select rifampin-resistant
mutants. The third control group (C) was a positive control that
included mice treated with the standard 6-month regimen, of 2 months of
daily (five times a week) isoniazid-rifampin-pyrazinamide followed by 4 months of daily isoniazid-rifampin (21). All five test
groups of mice were treated for a total of 6 months. Groups D to G
received once-weekly rifapentine plus isoniazid for 5.5 months,
supplemented with a 0.5-month initial daily phase of rifampin,
isoniazid, and pyrazinamide. In groups D and E, streptomycin was added
during either the daily initial plus the once-weekly continuation
phases or only the daily initial phase, respectively. In groups F and
G, similar to groups D and E, moxifloxacin was substituted for
streptomycin. In group H, all four drugs, rifapentine, isoniazid,
streptomycin, and moxifloxacin, were given once weekly from the start
of treatment.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3482-3486.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Effectiveness of Once-Weekly Rifapentine and Moxifloxacin
Regimens against Mycobacterium tuberculosis in
Mice
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
TABLE 1.
Experimental design in this study
13, D0, and D +14, respectively, in relation to
the initiation of treatment). From each treatment group, 20 mice were
sacrificed after 2 weeks to assess the contribution of streptomycin and
moxifloxacin during the daily initial phase. Similar groups of mice
were also sacrificed on completion of the 6-month course of therapy to
assess the ability of the different regimens to render the lungs of
mice culture negative. Groups of mice were held without treatment for 3 additional months and then sacrificed to measure the rate of relapse to
culture positivity.
Assessment of infection and treatment. Assessments of the severity of infection and the effectiveness of treatments were based on survival rate, spleen weights, gross lung lesions (the severity of which were scored from 0 to ++, the latter referring to a lung that was extensively occupied by tubercles), and total CFU counts in the lungs. At D0 and D +14, CFU counts in the lungs were determined by plating serial 10-fold dilutions of homogenized suspensions onto three Löwenstein-Jensen medium slants per dilution. On completion of treatment, the total amount of homogenized suspension from individual lungs was plated without dilution on 15 Löwenstein-Jensen slants. The results of the cultures were recorded after incubation at 37°C for 6 weeks. Testing of susceptibility to rifampin, isoniazid, and streptomycin was performed by the proportion method (1) with any colonies isolated from lung tissue at the end of treatment.
Statistical analysis.
Multiple comparisons among pairs of
group means were performed by Bonferroni's method (4).
Because five test groups were compared, differences were considered
significant at the level 0.005: i.e., 0.05/5(5 1)/2.
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RESULTS |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Survival rate. As expected, after intravenous infection with more than 106 CFU of the H37Rv strain, untreated control mice (group A) began to die from day 18 after infection, and all were dead by day 41. The survival rate of group B mice was 100%, indicating that the once-weekly dose of 10 mg of rifapentine per kg alone could effectively prevent deaths caused by infection with M. tuberculosis. In all treated groups, the survival rates were 90 to 100% during the first month of treatment. However, some mice died during treatment because of accidents during gavage or injection of streptomycin. Except for one mouse in group H (which died on D0) and three mice each in groups F (which died on D0, D1, and D2) and G (which died on D1, D2, and D2), all deaths (4 in group C, 6 in group D, 6 in group E, 6 in group F, 5 in group G, and 10 in group H) were due to gavage and/or injection accidents and were unrelated to tuberculosis.
Mean spleen weight.
The mean spleen weight of infected mice
increased more than fourfold during the initial 14 days after
infection. After 2 weeks of treatment, the mean spleen weights from
mice of groups C, D, F, and H were significantly smaller than that for
control mice sacrificed on D0 of treatment. The mean spleen weight of
mice supplemented with streptomycin (group D) was the lowest and
differed significantly from those of the other groups, except from the rifapentine-isoniazid-streptomycin-moxifloxacin group (Table
2). After 6 months of treatment, the mean
spleen weight did not differ significantly among the treated groups,
except for group E when compared to groups C and G (P = 0.001), all of which were significantly smaller than the pretreatment
(D0) value. These results indicate that all treatments were equally
effective in reversing the splenomegaly caused by tuberculosis
infection. At 9 months (i.e., at the end of the 3-month period of
follow-up), the mean spleen weights were similar to those at 6 months
for all the groups.
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Gross lung lesions. At onset of treatment, severe lung lesions (++) were observed in all sacrificed mice of group A. After 2 weeks of treatment (D +14), ++ lesions were still observed in all sacrificed mice of groups C, D, F, and H. However, on completion of 6 months of treatment, ++ lesions were observed only in 5 of 10 mice of group B, apparently due to the emergence of rifampin resistance (described below). After 3 months of follow-up, ++ lesions were observed in only a few mice of groups E (2 of 18), F (1 of 13), G (1 of 14), and H (1 of 12). These results indicate that the lung lesions caused by tuberculosis infection were progressively cured by treatment with all of the combination regimens, but not with rifapentine monotherapy.
Enumeration of CFU in the lungs.
The day after intravenous
infection, the mean CFU count in the lungs was 5.01 ± 0.17 log10. Two weeks later, it had increased, by about 1.5 log10 CFU, to reach 6.46 ± 0.33 log10 CFU. After 2 weeks of treatment, all mice
were culture positive, and the mean CFU counts in mice in groups C, D,
F, and H were significantly smaller (P < 10
5) than the pretreatment values (Table
3). The reduction in the CFU counts did
not differ significantly between mice in groups C and F and those in
groups C and H (P = 0.025 and 0.68, respectively). However, the reduction was significantly greater among the mice in
group D than among those in groups C and H (0.66 and 0.62 log10; P = 0.000001), indicating
the strong bactericidal activity of the initial daily supplement of
streptomycin. The difference between mice in groups D and F (0.36 log10 CFU; P = 0.006), suggested that the 100-mg/kg dose of moxifloxacin has somewhat less bactericidal activity than streptomycin.
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Prevention of resistance to isoniazid and rifapentine. Colonies isolated on completion of treatment were fully susceptible, indicating that under the experimental conditions presented, all regimens tested were able to prevent the selection of drug-resistant mutants.
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DISCUSSION |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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This experiment was designed to evaluate the possibility that moxifloxacin could replace streptomycin as the key companion drug in a highly effective once-weekly rifapentine-isoniazid combination for the treatment of murine tuberculosis. The experiment demonstrated that the overall antimicrobial activity of moxifloxacin compares favorably with that of streptomycin. When the daily rifampin-isoniazid-pyrazinamide combination was supplemented with moxifloxacin during the initial 2 weeks of therapy, the resulting increase in bactericidal activity was only marginally inferior to the increase resulting from a streptomycin supplement. On the other hand, when moxifloxacin was substituted for streptomycin as a companion drug of the rifapentine-isoniazid combination during the following 5.5 months of once-weekly therapy, the regimen's sterilizing activity was strongly increased. First, all 19 mice treated with moxifloxacin were culture negative on completion of the 6-month therapy, whereas 2 of 16 mice treated with streptomycin were still culture positive (with a single colony). Second, and more importantly, the relapse rates 3 months after treatment were 15% in mice treated with moxifloxacin and 61% in mice treated with streptomycin. The increased sterilizing activity provided by moxifloxacin may be specifically related to the administration of the fluoroquinolone during the 5.5 months of the continuation therapy, because in mice treated with moxifloxacin only during the 2-week daily initial phase, the relapse rate was 50%. In contrast, the relapse rates in mice treated with streptomycin during either the whole course of therapy or the 2-week initial daily phase only were similar: 61 and 55%, respectively. These results are consistent with streptomycin's recognized lack of sterilizing activity against M. tuberculosis in mice (6) and in humans (12). They suggest that moxifloxacin has excellent sterilizing activity, even when given only once weekly at the same dose as the daily dose. Such a conclusion is consistent with previous studies of use of fluoroquinolones against M. tuberculosis in the murine model (8, 9, 10, 13).
It is of great interest that the efficacy of therapy consisting of 2 weeks of daily rifampin, isoniazid, pyrazinamide, and moxifloxacin followed by a 5.5-month once-weekly treatment with rifapentine, isoniazid, and moxifloxacin was only marginally inferior to that of the 6-month daily standard regimen of 2 months of rifampin, isoniazid, and pyrazinamide followed by 4 months of rifampin and isoniazid. If the antimicrobial activity of the once-weekly regimen could be improved by increasing the once-weekly dose of rifapentine from the standard 10 mg/kg to 15 mg/kg and/or the once-weekly dose of moxifloxacin from 100 mg/kg to 400 mg/kg, such a regimen might be evaluated in clinical trials in patients with pulmonary tuberculosis, because it would be expected to be at least as potent as the standard 6-month daily regimen. Furthermore, recent data on moxifloxacin pharmacokinetics (15, 18) indicate that a dose of 400 mg/kg of body weight in mice would provide an AUC equivalent to that produced by 400 mg per day (7.5 mg/kg of body weight) in humans (16) and therefore that the activity of moxifloxacin in humans might be still greater than the excellent activity we observed in mice treated with 100 mg/kg.
In the present experiment, a full once-weekly drug regimen without an initial daily phase was also tested. Although this regimen contained both streptomycin and moxifloxacin and was able to prevent the emergence of drug-resistant mutants, its antimicrobial activity was not entirely satisfactory. Thus, for the present time, a daily initial phase of at least 2 weeks in duration appears essential in any once-weekly drug regimen.
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ACKNOWLEDGMENT |
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This work was supported by the Ministère des Affaires Etrangères (FAC 2000), Paris, France.
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FOOTNOTES |
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* Corresponding author. Mailing address: Laboratoire de Bactériologie-Hygiène, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris, Cedex 13, France. Phone: (33) 1 40 77 97 46. Fax: (33) 1 45 82 75 77. E-mail: lounis{at}chups.jussieu.fr.
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REFERENCES |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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| 1. | Canetti, G., N. Rist, and J. H. Grosset. 1963. Mesure de la sensibilité du bacille tuberculeux aux drogues antibacillaires par la méthode des proportions. Methodologie, critères de résistance, résultats, interprétation. Rev. Tuberc. Pneumol. 27:217-272. |
| 2. | Chapuis, L., B. Ji, C. Truffot-Pernot, R. J. O'Brien, M. C. Raviglione, and J. H. Grosset. 1994. Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice. Am. J. Respir. Crit. Care Med. 150:1355-1362[Abstract]. |
| 3. |
Daniel, N.,
N. Lounis,
B. Ji,
R. J. O'Brien,
A. Vernon,
L. J. Geiter,
M. Szpytma,
C. Truffot-Pernot,
G. Hejblum, and J. Grosset.
2000.
Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens.
Am. J. Respir. Crit. Care Med.
161:1572-1577 |
| 4. | Godfrey, K. 1985. Statistics in practice. Comparing the mean of several groups. N. Engl. J. Med. 313:1450-1456[Abstract]. |
| 5. |
Grosset, J.,
N. Lounis,
C. Truffot-Pernot,
R. J. O'Brien,
M. C. Raviglione, and B. Ji.
1998.
Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice.
Am. J. Respir. Crit. Care Med.
157:1436-1440 |
| 6. | Grumbach, F., G. Canetti, J. Grosset, and M. Le Lirzin. 1967. Late results of long-term intermittent chemotherapy of advanced murine tuberculosis. Limits of the murine model. Tubercle 48:11-26[Medline]. |
| 7. | Ji, B., C. Truffot-Pernot, M. C. Lacroix, M. C. Raviglione, R. J. O'Brien, P. Olliaro, G. Roscigno, and J. Grosset. 1993. Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. Am. Rev. Respir. Dis. 148:1541-1546[Medline]. |
| 8. |
Ji, B.,
N. Lounis,
C. Maslo,
C. Truffot-Pernot,
P. Bonnafous, and J. Grosset.
1998.
In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis.
Antimicrob. Agents Chemother.
42:2066-2069 |
| 9. |
Lalande, V.,
C. Truffot-Pernot,
A. Paccaly-Moulin,
J. Grosset, and B. Ji.
1993.
Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice.
Antimicrob. Agents Chemother.
37:407-413 |
| 10. | Lounis, N., B. Ji, C. Truffot-Pernot, and J. Grosset. 1997. Which aminoglycoside or fluoroquinolone is more active against Mycobacterium tuberculosis in mice? Antimicrob. Agents Chemother. 41:607-610[Abstract]. |
| 11. | Medical Economics Company, Inc. 1999. Physician's desk reference, p. 1334-1338. Medical Economics Company, Inc., Montvale, N.J. |
| 12. | Medical Research Council/Tuberculosis Chemotherapy Trials Committee. 1962. Long-term chemotherapy in the treatment of chronic pulmonary tuberculosis with cavitation. Tubercle 43:201-267. |
| 13. |
Miyazaki, E.,
M. Miyazaki,
J. M. Chen,
R. E. Chaisson, and W. Bishai.
1999.
Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis.
Antimicrob. Agents Chemother.
43:85-89 |
| 14. | Rowland, M., and T. N. Tozer. 1980. Clinical pharmacokinetics, concepts and applications. Lea and Febiger, Philadelphia, Pa. |
| 15. | Siefert, H. M., A. Domdey-Bette, K. Henninger, F. Hucke, C. Kohlsdorfer, and H. H. Stass. 1999. Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species. J. Antimicrob. Chemother. 43:69-76[Abstract]. |
| 16. | Stass, H., and D. Kubitza. 1999. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J. Antimicrob. Chemother. 43:83-90[Abstract]. |
| 17. |
Tam, C. M.,
S. L. Chan,
C. W. Lam,
C. C. Leung,
K. M. Kam,
J. S. Morris, and D. A. Mitchison.
1998.
Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis: initial report.
Am. J. Respir. Crit. Care Med.
157:1726-1733 |
| 18. | Von Keutz, E., and G. Schlüter. 1999. Preclinical safety evaluation of moxifloxacin, a novel fluoroquinolone. J. Antimicrob. Chemother. 43:83-90. |
| 19. | World Health Organization. 1994. WHO tuberculosis Programme. Framework for effective tuberculosis control. Publication no. W. H. O./94. 179. World Health Organization, Geneva, Switzerland. |
| 20. | World Health Organization. 1995. Proposed new strategy for global TB research: a report of the Fifth Meeting of the CARG. World Health Organization/GTB/Coordination. Advisory and Review Group for the tuberculosis programme/95.5. World Health Organization, Geneva, Switzerland. |
| 21. | World Health Organization. 1997. Treatment of tuberculosis: guidelines for national programmes, 2nd ed. Publication no. TB/97.220. World Health Organization, Geneva, Switzerland. |
Antimicrobial Agents and Chemotherapy, December 2001, p. 3482-3486, Vol. 45, No. 12
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3482-3486.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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(2003). In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with anti-tuberculosis agents. J Antimicrob Chemother
52: 1025-1028
[Abstract] [Full Text] -
O'Brien, R. J.
(2003). Development of Fluoroquinolones as First-line Drugs for Tuberculosis--at Long Last!. Am. J. Respir. Crit. Care Med.
168: 1266-1268
[Full Text] -
Veziris, N., Truffot-Pernot, C., Aubry, A., Jarlier, V., Lounis, N.
(2003). Fluoroquinolone-Containing Third-Line Regimen against Mycobacterium tuberculosis In Vivo. Antimicrob. Agents Chemother.
47: 3117-3122
[Abstract] [Full Text] -
Mitchison, D. A.
(2003). Role of Isoniazid in Once-Weekly Rifapentine Treatment of Pulmonary Tuberculosis. Am. J. Respir. Crit. Care Med.
167: 1298-1299
[Full Text] -
Weiner, M., Burman, W., Vernon, A., Benator, D., Peloquin, C. A., Khan, A., Weis, S., King, B., Shah, N., Hodge, T., the Tuberculosis Trials Consortium,
(2003). Low Isoniazid Concentrations and Outcome of Tuberculosis Treatment with Once-Weekly Isoniazid and Rifapentine. Am. J. Respir. Crit. Care Med.
167: 1341-1347
[Abstract] [Full Text] -
(2003). American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis. Am. J. Respir. Crit. Care Med.
167: 603-662
[Full Text] -
Hu, Y., Coates, A. R. M., Mitchison, D. A.
(2003). Sterilizing Activities of Fluoroquinolones against Rifampin-Tolerant Populations of Mycobacterium tuberculosis. Antimicrob. Agents Chemother.
47: 653-657
[Abstract] [Full Text] -
Fattorini, L., Tan, D., Iona, E., Mattei, M., Giannoni, F., Brunori, L., Recchia, S., Orefici, G.
(2003). Activities of Moxifloxacin Alone and in Combination with Other Antimicrobial Agents against Multidrug-Resistant Mycobacterium tuberculosis Infection in BALB/c Mice. Antimicrob. Agents Chemother.
47: 360-362
[Abstract] [Full Text] -
Yoshimatsu, T., Nuermberger, E., Tyagi, S., Chaisson, R., Bishai, W., Grosset, J.
(2002). Bactericidal Activity of Increasing Daily and Weekly Doses of Moxifloxacin in Murine Tuberculosis. Antimicrob. Agents Chemother.
46: 1875-1879
[Abstract] [Full Text] -
Bock, N. N., Sterling, T. R., Hamilton, C. D., Pachucki, C., Wang, Y.-C., Conwell, D. S., Mosher, A., Samuels, M., Vernon, A.
(2002). A Prospective, Randomized, Double-Blind Study of the Tolerability of Rifapentine 600, 900, and 1,200 mg Plus Isoniazid in the Continuation Phase of Tuberculosis Treatment. Am. J. Respir. Crit. Care Med.
165: 1526-1530
[Abstract] [Full Text]
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