Moxifloxacin-containing Regimens of Reduced Duration Produce a Stable Cure in Murine Tuberculosis

Nuermberger, Eric L.; Yoshimatsu, Tetsuyuki; Tyagi, Sandeep; Williams, Kathy; Rosenthal, Ian M.; O’Brien, Richard; Vernon, Andrew; Chaisson, Richard E.; Bishai, William R.; Grosset, J

doi:10.1164/rccm.200407-885oc

Cited by 211 publications

(182 citation statements)

References 14 publications

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“…Drugs were obtained and stock solutions were prepared as previously described (16). RPT tablets, donated by Sanofi-Aventis (Kansas City, MO), were ground into a powder and suspended in water before gavage.…”

Section: Antimicrobialsmentioning

confidence: 99%

“…Six-week-old female BALB/c mice were purchased from Charles River (Wilmington, MA) and infected as previously described (16). Mice were infected in four consecutive runs.…”

Section: Aerosol Infectionmentioning

confidence: 99%

“…After 4, 5, and 6 mo of therapy mice from each group went untreated for an additional 3 mo before being killed to assess the proportion of culture-positive mice. Colony-forming unit counts and body and spleen weights were determined as previously described (16). RIF susceptibility testing was performed by the agar proportion method.…”

Section: Assessment Of Treatment Efficacymentioning

confidence: 99%

“…Furthermore, in an early bactericidal activity study of the rifamycins it has been suggested that the most effective dose of RPT may lie between 15 and 20 mg/kg (13). Additional improvement of RPTbased regimens might come from incorporating moxifloxacin (MXF), a new fluoroquinolone with potent bactericidal against Mycobacterium tuberculosis and a half-life close to that of RPT (14)(15)(16). It has been demonstrated in the murine model that inclusion of MXF during the initial and continuation phases of a largely once-weekly INH-RPT 10 mg/kg regimen significantly improves sterilizing activity and prevents the selection of rifamycin monoresistance (14).…”

mentioning

confidence: 99%

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Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

Rosenthal

Williams

Tyagi

et al. 2005

Am J Respir Crit Care Med

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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: 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 highrisk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy ("Denver" regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy. Results: After 2 mo of treatment, lung colony-forming unit counts were 1 log 10 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 onceweekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen. Conclusions: These results suggest that the efficacy of the onceweekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg. Keywords: antibiotics; intermittent therapy; mouse; treatment Effective control of tuberculosis (TB), especially in the setting of the HIV pandemic, requires the use of long and cumbersome chemotherapeutic regimens (1). Despite implementation of the World Health Organization directly observed therapy shortcourse strategy, nonadherence remains a serious threat to effective control of TB (2). Effective regimens employing drugs that could be administered once weekly (1 of 7 d) would be expected to facilitate supervised therapy by reducing the number of doses requiring supervision (3), leading to improved completion rates and raising prospects for expansion of DOTS coverage throughout the developing world.Rifapentine (RPT), a long-lasting rifamycin, is currently recommended for use at a dose of 10 mg/kg in combination with isoniazid (INH) during once-weekly continuation phase therapy (4). However, treatment restrictions limit the use of INH-RPT to non-highrisk patients (HIV seronegative with noncavitary TB) and are based on higher rates of treatment failure or relapse with rifamycinmonoresistant bacilli in high-risk patients (3, 5). Moreover, once-weekly INH-RPT has been shown to be less active than three times-or twice-weekly (3 of 7 or 2 of ...

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Section: Antimicrobialsmentioning

confidence: 99%

“…Six-week-old female BALB/c mice were purchased from Charles River (Wilmington, MA) and infected as previously described (16). Mice were infected in four consecutive runs.…”

Section: Aerosol Infectionmentioning

confidence: 99%

Section: Assessment Of Treatment Efficacymentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

Rosenthal

Williams

Tyagi

et al. 2005

Am J Respir Crit Care Med

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“…However, due to lower cost, OFX is still being used for the treatment of MDR-TB patients in developing countries. Early studies carried out in murine models of TB suggested that replacement of EMB or INH with MFX in first-line treatment for TB has the potential to improve outcome and to shorten therapy to four months from the current standard of six months [40,41]. The maximum treatment benefit was noted when MFX was used in place of INH in the murine model of TB [40].…”

Section: Fluoroquinolones As Anti-tb Drugsmentioning

confidence: 99%

Role of fluoroquinolones in the treatment of tuberculosis

Ahmad

Mokaddas

2011

RHC

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Increasing Outpatient Fluoroquinolone Exposure Before Tuberculosis Diagnosis and Impact on Culture-Negative Disease

Gaba¹,

Haley²,

Griffin³

et al. 2007

Arch Intern Med

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Background: Fluoroquinolones are widely used to treat routine bacterial infections, but they are also potential firstline antituberculosis agents. Empirical fluoroquinolone therapy can delay the diagnosis of tuberculosis and cause resistance in Mycobacterium tuberculosis. Rates of fluoroquinolone exposure before tuberculosis diagnosis and the impact of fluoroquinolones on culture-negative tuberculosis have not been previously reported. Methods: All newly diagnosed tuberculosis cases reported to the Tennessee Department of Health between January 1, 2000, and December 31, 2004, were crossmatched with the TennCare (Medicaid) pharmacy database to assess for outpatient fluoroquinolone use in the 12 months before tuberculosis diagnosis. Results: Of 1562 tuberculosis cases reported, 1055 occurred in TennCare participants; of these 1055 TennCare patients, 507 were enrolled in TennCare more than 300 days during the year before tuberculosis diagnosis. Of the 507 patients, 119 (23%) received a fluoroquinolone before tuberculosis diagnosis. The proportion of fluoroquinolone-exposed patients increased from 9% in 2000 to 41% in 2004 (2 test for trend P Ͻ.001). In multivariate logistic regression analysis, factors associated with fluoroquinolone exposure were older age (odds ratio [OR], 1.03 per year; 95% confidence interval [CI], 1.02-1.04) and year of diagnosis (OR,1.64 per 1-year increase; 95% CI, 1.39-1.93); human immunodeficiency virus infection tended to be associated with increased exposure (OR,1.94; 95% CI, 0.97-3.90). After controlling for age, sex, race, site of disease, human immunodeficiency virus, and year of diagnosis, prior fluoroquinolone exposure was not associated with culture-negative tuberculosis (OR,0.81; 95% CI, 0.41-1.60). Conclusions: Fluoroquinolone use before tuberculosis diagnosis increased significantly during the study period. However, fluoroquinolone exposure was not associated with an increased risk of culture-negative tuberculosis.

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Moxifloxacin-containing Regimens of Reduced Duration Produce a Stable Cure in Murine Tuberculosis

Cited by 211 publications

References 14 publications

Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

Role of fluoroquinolones in the treatment of tuberculosis

Increasing Outpatient Fluoroquinolone Exposure Before Tuberculosis Diagnosis and Impact on Culture-Negative Disease

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