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Are we justified in treating for multidrug-resistant tuberculosis based on positive follow-up smear results?

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SETTING: National Institute for Research in Tuberculosis, India.

OBJECTIVE:To assess, among new culture-confirmed smear-positive pulmonary tuberculosis (TB) patients, the proportion of follow-up smear-positives that were culture-negative (S+C-) by month of follow-up examination, human immunodeficiency virus (HIV) status, pre-treatment drug susceptibility status and smear grading.

DESIGN: We extracted follow-up smear (fluorescence microscopy) and culture (Löwenstein-Jensen) results of patients enrolled in clinical trials from January 2000 to August 2012 and treated with the WHO Category I regimen (2EHRZ3/4HR3).

RESULTS: Of 520 patients, including 176 who were HIV-infected, respectively 199, 81, 47 and 43 were smear-positive at months 2, 4, 5 and 6; of these, respectively 138 (69%), 62 (75%), 32 (68%) and 27 (63%) were culture-negative. The S+C- phenomenon was more pronounced among ‘1+ positive' patients than in 2+ or 3+ positive patients and in ‘pan-susceptible' patients than in those with any resistance, and did not vary by HIV status.

CONCLUSION: Nearly two thirds of patients with follow-up smears positive at months 5 and 6 were culture-negative. Starting multidrug-resistant TB (MDR-TB) treatment empirically based on smear results, even in resource-limited settings, is incorrect and can have hazardous consequences. There is an urgent need to revisit the WHO recommendation concerning empirical MDR-TB treatment.

Keywords: S+C- phenomenon; empiric MDR-TB treatment; pulmonary tuberculosis; sputum culture; sputum smear

Document Type: Research Article

Affiliations: 1: National Institute for Research in Tuberculosis, Chennai, India 2: International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office, New Delhi, India; 3: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

Publication date: April 1, 2014

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