Effectiveness of Once-Weekly Rifapentine and Moxifloxacin Regimens against Mycobacterium tuberculosis in Mice

Abstract

Mice infected with 1.6 x 10(7) 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.

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

“…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).…”

“…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). However, it is unknown whether the addition of MXF to INH-RPT or substitution of MXF for INH would confer the greatest increase in sterilizing activity.…”

Schneller Nachweis von Mutationen im gyrA-Gen von Mycobacterium tuberculosis mit Relevanz für die Entstehung von Medikamentenresistenzen gegen Chinolone mittels der Real-Time PCR auf dem LightCycler® System

“…Moxifloxacin im Tierversuch auch eine sterilisierende, d.h. eine auf sich nicht replizierende Bakterien wirkende Komponente (Lounis, Bentoucha et al 2001). …”

A meta analysis of the efficacy and safety of moxifloxacin in Chinese patients with multi-drug resistant pulmonary tuberculosisosis

“…Moxifloxacin is a fluoroquinolone that has potent in-vitro activity against MDR-TB (Ji et al, 1998;Gillespie and Billington, 1999). Earlier studies of moxifloxacin in murine models of tuberculosis showed that it had good bactericidal activity that was additive to isoniazi (Miyazaki et al, 1999;Lounis et al, 2001). Though there are several clinic studies (Burman et al, 2006;Conde et al, 2009;Dorman et al, 2009) about moxifloxacin in treatment of MDR-TB, the conclusions of which are not credible because of small sample size and lacks of systemic evaluation of methodologic quality.…”