title: Systematic screening for drug-resistant tuberculosis with Xpert(®) MTB/RIF in a referral hospital in Cambodia.
abstract: METHODS
  Limited access to drug susceptibility testing (DST) in referral hospitals contributes to delayed detection of multidrug-resistant tuberculosis (MDR-TB).
  
  
  OBJECTIVE
  To document the impact of identifying rifampicin (RMP) resistance using Xpert(®) MTB/RIF on time to diagnosis and time to treatment, and evaluate its performance under programmatic conditions.
  
  
  METHODS
  Using a prospective observational study, we screened presumptive MDR-TB cases with Xpert and solid culture/conventional DST. RMP resistance was confirmed using a line-probe assay (LPA). We recorded diagnostic and treatment delays. We performed rpoB gene sequencing post hoc to resolve discordant RMP susceptibilities.
  
  
  RESULTS
  We screened 299 of 345 presumptive MDR-TB individuals, and identified 44 Xpert RMP-resistant cases: 16/165 (10%) were new and 28/136 (20%) retreated. The median time to diagnosis was 2 days (Xpert) vs. an additional 6 with LPA; the median time to treatment was 14 days. Confirmatory LPA on 39/44 revealed 27 concordant, 6 discordant and 6 invalid results. Xpert RMP resistance was confirmed in respectively 24/30 (80%) and 21/23 (91%) by phenotypic DST and rpoB sequencing.
  
  
  CONCLUSIONS
  Screening presumptive MDR-TB patients with Xpert enabled rapid diagnosis and treatment of MDR-TB. Xpert performed well, provided appropriate risk assessment was done. Rapid confirmatory testing added little to clinical decision making. Our findings support the latest World Health Organization guidelines to abandon confirmatory LPA in favour of repeat Xpert when in clinical doubt, pending phenotypic DST.
authors.affiliation: Infectious Diseases Department, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Lorent
authors.affiliation: Infectious Diseases Department, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: C
authors.initials: C
authors.lastname: Kong
authors.affiliation: Mycobacteriology Laboratory, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: T
authors.initials: T
authors.lastname: Kim
authors.affiliation: Cambodian Health Committee, Phnom Penh, Cambodia.
authors.forename: S
authors.initials: S
authors.lastname: Sam
authors.affiliation: Infectious Diseases Department, Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia.
authors.forename: S
authors.initials: S
authors.lastname: Thai
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Colebunders
authors.affiliation: Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Rigouts
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Lynen
mesh_terms: D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D002160:Cambodia; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D011446:Prospective Studies; D012017:Referral and Consultation; D012293:Rifampin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D061665:Time-to-Treatment; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin