Detection of Resistance to Second-Line Antituberculosis Drugs by Use of the Genotype MTBDR sl Assay: a Multicenter Evaluation and Feasibility Study

Abstract

eThe rate of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has been steadily increasing in countries of the former USSR. The availability of rapid and reliable methods for the detection of drug resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the Genotype MTBDRsl assay compared to that of phenotypic drug susceptibility testing (Becton Dickinson Bactec MGIT 960 system) with a test panel of 200 Mycobacterium tuberculosis isolates at four sites in Eastern Europe. The interpretability of the Genotype MTBDRsl assay was over 95%. The sensitivity for the detection of resistance to fluoroquinolones, ethambutol, amikacin, and capreomycin varied between 77.3% and 92.3%; however, it was much lower for kanamycin (42.7%). The sensitivity for the detection of XDR TB was 22.6%. The test specificity was over 82% for all drugs. The assay presents a good screening tool for the rapid detection of resistance to individual second-line drugs and can be recommended for use in countries with a high burden of MDR/XDR TB. The sensitivity for the detection of kanamycin resistance needs improvement.

Evaluation of the BACTEC MGIT 960 SL DST Kit and the GenoType MTBDRsl Test for Detecting Extensively Drugresistant Tuberculosis Cases

“…Our results were consistent with those of Ignatyeva et al [16]. However, the sensitivity rate for OFL in our study was higher than those reported by Tukvadze et al [17] and Jin et al [18].…”

“…In addition to higher sensitivity rate for KAN, our results were similar to those of Ignatyeva et al [16] and Huang et al [22] and to those Theron et al [19] highlighted in their review article. Resistance to KAN can occur with eis promoter gene regions other than rrs regions, which are commonly responsible for resistance to AG/CPs.…”

Diagnostic Accuracy of the GenoType MTBDR sl Assay for Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis in HIV-Coinfected Patients

“…Controversies regarding sensitivity rates of the assay reported in previous studies, especially for AGs and CPs and for KAN in particular (15,16,(21)(22)(23), could be attributed to the diverse genetic background of strains and different distribution of mutations conferring drug resistance in different geographic settings. In recent studies conducted on clinical strains isolated in Estonia, Vietnam, and South Africa, the sensitivity of the assay for the detection of resistance to KAN was very low (reaching 43% at its maximum) (16,22,23), probably due to the high prevalence of Beijing strains harboring mutations in eis genes not recognized by the assay and responsible for conferring resistance to KAN only, as was shown in Vietnam (23).…”

“…In recent studies conducted on clinical strains isolated in Estonia, Vietnam, and South Africa, the sensitivity of the assay for the detection of resistance to KAN was very low (reaching 43% at its maximum) (16,22,23), probably due to the high prevalence of Beijing strains harboring mutations in eis genes not recognized by the assay and responsible for conferring resistance to KAN only, as was shown in Vietnam (23). Absence of cross-resistance to AMK and CAP in strains harboring mutations in the eis promoter region has been recently demonstrated in a genomic study of resistance in Samara, Russia (24), and in another study conducted in Russia (25).…”

“…The assay has been evaluated in two low-incidence TBand HIV settings, predominantly on cultures as well as patient specimens, and demonstrated good sensitivity and specificity (13,14). Assay performance varied significantly depending on the genetic background of the strains and tended to be lower with Eastern European strains (15,16). Currently, only limited systematic data are available on the performance of molecular assays for the direct diagnosis of resistance to RIF and INH in specimens from patients in settings of high TB burden and high HIV prevalence (17,18); the sensitivity and specificity of LPAs for the detection of resistance to SLD in specimens from HIV-infected TB patients are unknown.…”