RATIONALE: Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality. OBJECTIVES: To assess the diagnostic performance of the GenoType MTBDRsl line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and ethambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory. METHODS: Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRsl LPA. The diagnostic performance was assessed relative to the "gold standard" culture-based method, and the laboratory turnaround times for both methods were determined. MEASUREMENTS AND MAIN RESULTS: A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRsl LPA, was 90.7% (95% confidence interval [CI], 80.1-96.0%), 100% (95% CI, 91.8-100%), and 92.3% (95% CI, 75.9-97.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3-99.0%), 99.4% (95% CI, 98.2-99.8%), and 99.6% (95% CI, 98.5-99.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P < 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P < 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability. CONCLUSIONS: The GenoType MTBDRsl LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnostic yield (P < 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome.
RATIONALE: Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality. OBJECTIVES: To assess the diagnostic performance of the GenoType MTBDRsl line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and ethambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory. METHODS: Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRsl LPA. The diagnostic performance was assessed relative to the "gold standard" culture-based method, and the laboratory turnaround times for both methods were determined. MEASUREMENTS AND MAIN RESULTS: A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRsl LPA, was 90.7% (95% confidence interval [CI], 80.1-96.0%), 100% (95% CI, 91.8-100%), and 92.3% (95% CI, 75.9-97.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3-99.0%), 99.4% (95% CI, 98.2-99.8%), and 99.6% (95% CI, 98.5-99.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P < 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P < 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability. CONCLUSIONS: The GenoType MTBDRsl LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnostic yield (P < 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome.
Authors: C Ritter; K Lucke; F A Sirgel; R W Warren; P D van Helden; E C Böttger; G V Bloemberg Journal: J Clin Microbiol Date: 2014-01-08 Impact factor: 5.948
Authors: S-Y Grace Lin; Timothy C Rodwell; Thomas C Victor; Errin C Rider; Lucy Pham; Antonino Catanzaro; Edward P Desmond Journal: J Clin Microbiol Date: 2013-11-27 Impact factor: 5.948
Authors: Keertan Dheda; Tawanda Gumbo; Neel R Gandhi; Megan Murray; Grant Theron; Zarir Udwadia; G B Migliori; Robin Warren Journal: Lancet Respir Med Date: 2014-03-24 Impact factor: 30.700
Authors: William A Wells; Catharina C Boehme; Frank G J Cobelens; Colleen Daniels; David Dowdy; Elizabeth Gardiner; Jan Gheuens; Peter Kim; Michael E Kimerling; Barry Kreiswirth; Christian Lienhardt; Khisi Mdluli; Madhukar Pai; Mark D Perkins; Trevor Peter; Matteo Zignol; Alimuddin Zumla; Marco Schito Journal: Lancet Infect Dis Date: 2013-03-24 Impact factor: 25.071
Authors: A P Trollip; D Moore; J Coronel; L Caviedes; S Klages; T Victor; E Romancenco; V Crudu; K Ajbani; V P Vineet; C Rodrigues; R L Jackson; K Eisenach; R S Garfein; T C Rodwell; E Desmond; E J Groessl; T G Ganiats; A Catanzaro Journal: Int J Tuberc Lung Dis Date: 2014-02 Impact factor: 2.373
Authors: Michel K Kaswa; Muriel Aloni; Léontine Nkuku; Brian Bakoko; Rossin Lebeke; Albert Nzita; Jean Jacques Muyembe; Bouke C de Jong; Pim de Rijk; Jan Verhaegen; Marleen Boelaert; Margareta Ieven; Armand Van Deun Journal: J Clin Microbiol Date: 2014-05-28 Impact factor: 5.948