A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis
Abstract: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.
Document Type: Regular Paper
Affiliations: 1: Unit for Clinical and Biomedical TB Research, Medical Research Council (MRC), Durban, South Africa 2: Institut de Recherche pour le Développement, Paris, France; and International Union Against Tuberculosis and Lung Disease, Paris, France 3: Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland 4: Wellcome Centre for Clinical Tropical Medicine/Department of Pharmacology, University of Liverpool, Liverpool, UK 5: Biostatics Unit, Medical Research Council, Pretoria, South Africa 6: Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of KwaZulu Natal, South Africa 7: Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, Tygerberg, South Africa 8: Division of Cellular & Molecular Medicine, St George's, University of London, London, UK
Publication date: 2008-02-01
The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.
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