title: Implementation of genotype MTBDRplus reduces time to multidrug-resistant tuberculosis therapy initiation in South Africa.
abstract: BACKGROUND
  Diagnosis of drug resistance and timely initiation of multidrug-resistant (MDR) tuberculosis therapy are essential to reduce transmission and improve patient outcomes. We sought to determine whether implementation of the rapid MTBDRplus diagnostic shortened the time from specimen collection to patient MDR tuberculosis therapy initiation.
  
  
  METHODS
  We conducted a retrospective cohort analysis of 197 MDR tuberculosis patients treated at Brewelskloof, a rural tuberculosis hospital in Western Cape Province, South Africa, between 2007 and 2011.
  
  
  RESULTS
  Eighty-nine patients (45%) were tested using conventional liquid culture and drug susceptibility testing (DST) on solid medium and 108 (55%) were tested using the MTBDRplus assay after positive acid-fast bacilli or culture. Median time from sample taken to therapy initiation was reduced from 80 days (interquartile range [IQR] 62-100) for conventional DST to 55 days (IQR 37.5-78) with the MTBDRplus. Although the laboratory processing time declined significantly, operational delays persisted both in the laboratory and the clinical infrastructure for getting patients started on treatment. In multivariate analysis, patients tested using the MTBDRplus test had a reduced risk of starting treatment 60 days or more after sputum collection of 0.52 (P < .0001) compared with patients tested with culture-based DST, after adjustment for smear status and site of disease.
  
  
  CONCLUSIONS
  Use of MTBDRplus significantly reduced time to MDR tuberculosis treatment initiation. However, DST reporting to clinics was delayed by more than 1 week due, in part, to laboratory operational delays, including dependence on smear and culture positivity prior to MTBDRplus performance. In addition, once MDR tuberculosis was reported, delays in contacting patients and initiating therapy require improvements in clinical infrastructure.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. krjacobson@partners.org
authors.forename: Karen R
authors.initials: KR
authors.lastname: Jacobson
authors.forename: Danie
authors.initials: D
authors.lastname: Theron
authors.forename: Emily A
authors.initials: EA
authors.lastname: Kendall
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.forename: Marinus
authors.initials: M
authors.lastname: Barnard
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Tommie C
authors.initials: TC
authors.lastname: Victor
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Streicher
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
authors.forename: Robin M
authors.initials: RM
authors.lastname: Warren
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013019:South Africa; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents