title: The thin-layer agar method for direct phenotypic detection of multi- and extensively drug-resistant tuberculosis.
abstract: BACKGROUND
  Molecular techniques rapidly detect resistance to rifampicin (RMP) and isoniazid (INH), but do not eliminate the need for culture-based drug susceptibility testing (DST) against other drugs. The thin-layer agar (TLA) test, a non-commercial direct DST method, has demonstrated good performance for INH and RMP; however, evidence is still limited, and its applicability for DST of ofloxacin (OFX) and kanamycin (KM) is unknown.
  
  
  METHODS
  We compared 279 TLA DST results with those of MGIT for INH and RMP, and 280 results for OFX and KM with those of the 7H11 agar proportion method, obtained from 320 smear-positive samples from 165 Georgian TB patients. Discrepancies were solved by comparison with a composite reference standard. The prevalence of multidrug-resistant tuberculosis (TB) was 30 of 164 patients (18.3%), 2 (6.7%) of whom had extensively drug-resistant TB.
  
  
  RESULTS
  TLA showed 94.7%, 98.2%, 100% and 78.9% sensitivity, respectively, for INH, RMP, OFX and KM, with 100% specificity. Average time to results was 7 days in TLA, 23 in MGIT and 49 for 7H11 agar.
  
  
  CONCLUSIONS
  In low-resource settings, TLA can be applied for the rapid detection of resistance to INH, RMP and fluoroquinolones. Further studies are necessary to improve sensitivity to KM and further assess its performance for OFX and other drugs and its applicability in field conditions.
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium; Médecins Sans Frontières, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Ardizzoni
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Mulders
authors.affiliation: National Tuberculosis Programme, Tbilisi, Georgia.
authors.forename: T
authors.initials: T
authors.lastname: Kotrikadze
authors.affiliation: National Tuberculosis Programme, Tbilisi, Georgia.
authors.forename: R
authors.initials: R
authors.lastname: Aspindzelashvili
authors.affiliation: National Tuberculosis Programme, Tbilisi, Georgia.
authors.forename: L
authors.initials: L
authors.lastname: Goginashvili
authors.affiliation: Médecins Sans Frontières, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Pangtey
authors.affiliation: Médecins Sans Frontières, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Varaine
authors.affiliation: Epicentre, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bastard
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Rigouts
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium;New York University, New York, New York, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D015242:Ofloxacin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D007612:Kanamycin; D015242:Ofloxacin; D007538:Isoniazid; D012293:Rifampin