• R Rustomjee, C Lienhardt, T Kanyok, G R Davies, J Levin, T Mthiyane, C Reddy, A W Sturm, F A Sirgel, J Allen, D J Coleman, B Fourie, D A Mitchison, and Gatifloxacin for TB (OFLOTUB) study team.
• Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban, South Africa.
• Int. J. Tuberc. Lung Dis. 2008 Feb 1;12(2):128-38.

SettingCurrent treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs).ObjectivesA 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).DesignA 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.ResultsAfter 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.ConclusionsGFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.

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