title: Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.
abstract: METHODS
  Public ambulatory care centers in three districts of northern metropolitan Lima, Peru.
  
  
  OBJECTIVE
  To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC).
  
  
  METHODS
  Case series.
  
  
  RESULTS
  In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru.
  
  
  CONCLUSIONS
  In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. mbecerra@post.harvard.edu
authors.forename: M C
authors.initials: MC
authors.lastname: Becerra
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: J
authors.initials: J
authors.lastname: Bayona
authors.forename: S S
authors.initials: SS
authors.lastname: Shin
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.forename: J J
authors.initials: JJ
authors.lastname: Furin
authors.forename: B
authors.initials: B
authors.lastname: Werner
authors.forename: A
authors.initials: A
authors.lastname: Sloutsky
authors.forename: R
authors.initials: R
authors.lastname: Timperi
authors.forename: M E
authors.initials: ME
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Pagano
authors.forename: P E
authors.initials: PE
authors.lastname: Farmer
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003906:Developing Countries; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D010568:Peru / Q000453:epidemiology; D018570:Risk Assessment; D012494:Sampling Studies; D017211:Treatment Failure; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D000995:Antitubercular Agents