SETTING: Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs). OBJECTIVES: A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX). DESIGN: A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks. RESULTS: After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks. CONCLUSIONS:GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.
RCT Entities:
SETTING: Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs). OBJECTIVES: A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX). DESIGN: A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks. RESULTS: After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks. CONCLUSIONS:GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.
Authors: Rokeya Tasneen; Si-Yang Li; Charles A Peloquin; Dinesh Taylor; Kathy N Williams; Koen Andries; Khisimuzi E Mdluli; Eric L Nuermberger Journal: Antimicrob Agents Chemother Date: 2011-09-19 Impact factor: 5.191
Authors: Marc Weiner; Thomas J Prihoda; William Burman; John L Johnson; Stefan Goldberg; Nesri Padayatchi; Paula Duran; Melissa Engle; Grace Muzanye; Roy D Mugerwa; A Willem Sturm Journal: J Clin Microbiol Date: 2010-10-06 Impact factor: 5.948
Authors: Zahoor Ahmad; Austin Minkowski; Charles A Peloquin; Kathy N Williams; Khisimuzi E Mdluli; Jacques H Grosset; Eric L Nuermberger Journal: Antimicrob Agents Chemother Date: 2011-01-31 Impact factor: 5.191
Authors: Si-Yang Li; Scott M Irwin; Paul J Converse; Khisi E Mdluli; Anne J Lenaerts; Eric L Nuermberger Journal: Antimicrob Agents Chemother Date: 2015-04-27 Impact factor: 5.191
Authors: Susan E Dorman; Radojka M Savic; Stefan Goldberg; Jason E Stout; Neil Schluger; Grace Muzanyi; John L Johnson; Payam Nahid; Emily J Hecker; Charles M Heilig; Lorna Bozeman; Pei-Jean I Feng; Ruth N Moro; William MacKenzie; Kelly E Dooley; Eric L Nuermberger; Andrew Vernon; Marc Weiner Journal: Am J Respir Crit Care Med Date: 2015-02-01 Impact factor: 21.405