title: [Evaluation of GenoType MTBDRsl for testing resistance of Mycobacterium tuberculosis isolates to fluoroquinlone, aminoglycoside, and ethambutol].
abstract: OBJECTIVE
  To evaluate the ability of GenoType MTBDRsl (Hain Lifescience, Germany) in detecting resistance to fluoroquinolone (FQ), aminoglycoside (AG), and ethambutol (EB).
  
  
  METHODS
  We evaluated the resistance of 76 Mycobacterium tuberculosis samples, namely, 13 extensively drug-resistant (XDR), 29 multi-drug resistant (MDR), and 4 susceptible clinical isolates from Japan, and 30 strains from Supra-national Reference Laboratory Network, to FQ, AG, and EB by using GenoType MTBDRs. The gyrA, rrs, and embB were directly sequenced for all the strains, and the mutations were confirmed. The susceptibility testing result obtained using the standard proportion method with 1% Ogawa medium was considered as the gold standard.
  
  
  RESULTS
  The sensitivities of GenoType TBDRsl listance to FQ, kanamycin (KM), amikacin (AMK), capreomycin (CPM), and EB were 82.4%, 57.1%, 100%, 83.3%, and 55.8%, respectively. The specificity for FQ was 97.6%, and that for KM, AMK, CPM, and EB were 100%. The mutant strains detected by GenoType TBDRsl ere as follows: in 20 Japanese FQ resistant isolates, 7 gyrA MUT3A (D94A) (35.0%), 6 MUT3C (D94G) (30.0%), 2 MUT1 (A90V) (10.0%), and 1 MUT1 with MUT3C (5.0%); in 18 KM resistant isolates, 10 rrs MUT1 (A1401G) (55.6%); and in 34 EB resistant isolates, 9 embB MUT1B (M306V) (26.5%), 2 MUT1A (M306I) (5.9%), and 8 WT1 deficits (covering codon 306; 23.5%). Direct sequencing showed additional substitutions in embB (2 D328Y, 1 D354A, 1 G406D, and 1 G406S). The sensitivity of GenoType" MTBDRsl ws simillr to that by sequencing method for resistance to FQ and AG, but that for EB was slightly less than by sequencing method, but the difference was not significant.
  
  
  CONCLUSIONS
  The sensitivity of GenoType MTBDRsl for the letection of FQ resistance was approximately 80% to that by standard drug sensitivity test results by using conventional proportion methods, while it was relatively less accurate for the diagnosis of resistance to KM and EB in Japanese isolates. Thus, GenoType MTBDRsl is useful lr the early diagnosis and infection control of XDR-TB, because of a short turnaround time of approximately 6 h.
authors.affiliation: Bacteriology Division, Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. chikamatsu@jata.or.jp
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Chikamatsu
authors.forename: Akio
authors.initials: A
authors.lastname: Aono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mitarai
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D004977:Ethambutol / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000295:instrumentation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D004977:Ethambutol