title: Are we justified in treating for multidrug-resistant tuberculosis based on positive follow-up smear results?
abstract: METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: R S
authors.initials: RS
authors.lastname: Kumar
authors.affiliation: International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office, New Delhi, India;
authors.forename: A M V
authors.initials: AM
authors.lastname: Kumar
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Claassens
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: V V
authors.initials: VV
authors.lastname: Banurekha
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: G
authors.initials: G
authors.lastname: Sekar
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: P
authors.initials: P
authors.lastname: Venkatesan
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: S
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001431:Bacteriological Techniques; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D018579:Patient Selection; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D019564:Unnecessary Procedures; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents