title: Analysis of discrepant results between the Genotype®MTBDRplus assay and an antimicrobial drug susceptibility test for isoniazid-resistant tuberculosis.
abstract: We investigated discrepant results determined using the Genotype®MTBDRplus assay and a conventional antimicrobial drug susceptibility test (ADST) for isoniazid (INH) resistance using sequencing analysis and analyzed the clinical course of patients with discrepant results.
  
  
  
  Among 1373 MTBDRplus assays performed at our tertiary referral center in South Korea between August 2009 and December 2015, the results for 46 (3.4%) differed from those for ADST. KatG and inhA gene sequencing analysis results were available for 23 patients. ADSTs were carried out using the absolute concentration method with Löwenstein-Jensen media.
  
  
  
  Results from 11 patients indicated INH susceptibility by MTBDRplus assay and INH resistance by ADST. For 5 of these patients, sequencing revealed no evidence of mutations, whereas specific mutations were detected in the remaining 6 patients. These should have been detected using the MTBDRplus assay. The other 12 patients had isolates with the opposite discrepancy, that is INH resistance by MTBDRplus assay but INH susceptibility by ADST. For 7 of these cases, sequencing results were consistent with those of the MTBDRplus assay. However, sequencing analysis did not explain the discrepancies in the remaining 5 patients. All 23 patients with discrepant results received individualized treatment regimens determined by the attending physician according to their test results and susceptibility to other drugs, such as rifampin. Good outcomes were reported for the majority.
  
  
  
  Discrepancies between test results for INH resistance on the MTBDRplus assay and ADST appear to be infrequent. Gene sequencing analysis is useful for identifying the cause of the discrepancy.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Kyung-Wook
authors.initials: KW
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine, Chunggu Sungshim Hospital, South Korea.
authors.forename: Yoomi
authors.initials: Y
authors.lastname: Yeo
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Heungsup
authors.initials: H
authors.lastname: Sung
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: shimts@amc.seoul.kr.
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Shim
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics; D056910:Republic of Korea; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA / Q000379:methods; D016896:Treatment Outcome; D014376:Tuberculosis / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D007538:Isoniazid; D012293:Rifampin
keywords: Discrepancy; Isoniazid; KatG gene sequencing; MTBDRplus assay; inhA gene sequencing