A phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis

Rustomjee R. ; Lienhardt C. ; Kanyok T. ; Davies G.R. ; Levin J. ; Mthiyane T. ; Reddy C. ; Sturm A.W. ; Sirgel F.A. ; Allen J. ; Coleman D.J. ; Fourie B. ; Mitchison D.A. ; Bah-Sow O.Y. ; Diop H. ; Fielding K. ; Gninafon M. ; Mitchison D. ; Lienhardt C. ; Odhiambo J. ; Perronne C. ; Portaels F. ; Rustomjee R. ; Ramjee A. ; Master I. ; Olowolagba A. ; Chinappa T. ; Osburne G. ; Bamber S. ; Pala A.S. ; Pillay L. ; Tembe C. ; Mpangase P. ; Hadebe T. ; Ngcobo C.P. ; Mkhize Z. ; Dlamini C.N. ; Gill L. ; Dube T. ; Saul M. ; Merle C. ; Suma K.F. (2008)


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 biexponential 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. © 2008 The Union.

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