GenoType ® MTBDRplus Compared With Conventional Drug-Susceptibility Testing Of Mycobacterium Tuberculosis In A Low-Resistance Locale

Abstract

To determine the diagnostic accuracy of Geno Type® MTBDRplus compared with conventional proportional method (PM) drug susceptibility testing (DST) for detecting drug resistance of Mycobacterium tuberculosis (MTB) clinical isolates derived from the University Hospital of Heraklion, Crete, Greece. All MTB clinical isolates obtained between January 2000 and May 2009 were tested prospectively using the PM DST. All isolates were also tested either prospectively (strains isolated after January 2006; n = 140) or retrospectively (January 2000-December 2005; n = 81) using MTBDRplus. Among the 221 MTB isolates tested, 19 were resistant to isoniazid based on PM DST. The MTBDRplus assay identified 18 INH-resistant strains. Of these, 12 strains gave positive hybridization results with the mutation-specific probe katG Ser315Thr. The other six INH-resistant strains carried the mutation 15C→T in the inhA promoter region. One INH-sensitive strain, as determined by PM DST, had a katG gene mutation. The sensitivity, specificity, and positive and negative predictive values of MTBDRplus for INH were 89.5, 99.5, 94.7 and 99%, respectively. The single rifampicin-resistant strain that was also the only multidrug resistance isolate gave a positive hybridization result with the mutation-specific probe MUT1: D516V, which confers resistance to rifampicin. Despite the advantages of MTBDRplus (turn-around time of only 1 working day) compared with PM DST, the latter is still required in every case of a MTB clinical isolate, as the molecular assay does not detect 100% of drug resistance, especially INH resistance.