Evaluation of the GenoType® MTBDR<i>sl</i> assay for susceptibility testing of second-line anti-tuberculosis drugs

Said, Halima M.; Kock, Marleen M.; Ismail, Nazir; Baba, Kamaldeen; Omar, Shaheed V.; Osman, Ayman G.; Hoosen, Anwar A.; Ehlers, M.M.

doi:10.5588/ijtld.10.0600

Cited by 29 publications

(31 citation statements)

References 19 publications

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“…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).…”

Section: Discussionmentioning

confidence: 92%

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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cThe Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the eis gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…Therefore, resistant strains can easily be judged as susceptible, when embB 306 is used as the detection target, by mistake. The specificity showed large variations among different studies in genotype GenoType MTBDRsl group and lower pooled specificity than other groups due to the low specificities (0.55, 0.56) of two included studies (29,31) with large sample sizes. In the study by Said et al (31), all of the isolates were MDR, whereas Hazbón et al (49) reported that embB 306 mutations that may be associated with MDR and that MDR isolates phenotypically susceptible to EMB carried mutations at codon 306 of the embB gene.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies reported a high agreement between GenoType MTBDRsl and PCR-DNA sequencing (24,25,28,31). Pyrosequencing can provide the same accuracy as the sequencing method (38); thus, we considered the studies that used the three molecular assays for the detection of EMB resistance as a group in order to stratify by type of reference standard.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of a Molecular Drug Susceptibility Testing Method for the Antituberculosis Drug Ethambutol: a Systematic Review and Meta-Analysis

Song

Cui

et al. 2014

J Clin Microbiol

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b Ethambutol (EMB) is a first-line antituberculosis drug; however, drug resistance to EMB has been increasing. Molecular drug susceptibility testing (DST), based on the embB gene, has recently been used for rapid identification of EMB resistance. The aim of this meta-analysis was to establish the accuracy of molecular assay for detecting drug resistance to EMB. PubMed, Embase, and Web of Science were searched according to a written protocol and explicit study selection criteria. Measures of diagnostic accuracy were pooled using a random effects model. A total of 34 studies were included in the meta-analysis. The respective pooled sensitivities and specificities were 0.57 and 0.93 for PCR-DNA sequencing that targeted the embB 306 codon, 0.76 and 0.89 for PCR-DNA sequencing that targeted the embB 306, 406, and 497 codons, 0.64 and 0.70 for detecting Mycobacterium tuberculosis isolates, 0.55 and 0.78 for detecting M. tuberculosis sputum specimens using the GenoType MTBDRsl test, 0.57 and 0.87 for pyrosequencing, and 0.35 and 0.98 for PCR-restriction fragment length polymorphism. The respective pooled sensitivities and specificities were 0.55 and 0.92 when using a lower EMB concentration as the reference standard, 0.67 and 0.73 when using a higher EMB concentration as the reference standard, and 0.60 and 1.0 when using multiple reference standards. PCR-DNA sequencing using multiple sites of the embB gene as detection targets, including embB 306, 406, and 497, can be a rapid method for preliminarily screening for EMB resistance, but it does not fully replace phenotypic DST. Of the reference DST methods examined, the agreement rates were the best using MGIT 960 for molecular DST and using the proportion method on Middlebrook 7H10 media.T uberculosis (TB) is one of the most serious infectious diseases in the world. According to the 2013 Global Tuberculosis report by the World Health Organization (WHO), in 2012 an estimated 450,000 people developed multidrug-resistant TB (MDR-TB), and there were approximately 170,000 deaths due to MDR-TB worldwide (1). MDR-TB and extensively drug-resistant TB (XDR-TB) are among the greatest threats to the success of TB control in the world (2, 3). Ethambutol (EMB) is one of the firstline drugs included in the directly observed, treatment shortcourse antitubercular regimen recommended by the WHO (3). EMB is commonly used in combination with isoniazid (INH), rifampin (RIF), and pyrazinamide to treat TB, particularly when treating MDR-TB and XDR-TB (3). EMB has also been found to protect companion drugs against resistance, particularly INH (4). Initially, EMB was effective for preventing treatment failures caused by M. tuberculosis isolates resistant to other anti-TB drugs; however, the resistance rate of EMB has gradually increased in some regions and is close to 50% in TB patients that are retreated (5-7). In China, the resistance rate for EMB increased from 6.52% in 2007 to 17. 18% in 2010 (8). Therefore, rapid and effective methods of drug susceptibility testing (DST) for M. tuberculos...

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“…Some studies in China, Vietnam, and South Africa revealed that the most frequent mutations are D94G (gyrA) (36.5%) and A1401G (rrs) (42.1%) in China, D94G (54%) and A1401G (80%) in Vietnam, and D94G (42.4%) in South Africa; these were the most frequent mutations also detected in Colombian strains (4,21,26).…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia

et al. 2013

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Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first-and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first-and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases.

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Evaluation of the GenoType® MTBDRsl assay for susceptibility testing of second-line anti-tuberculosis drugs

Abstract: Background: The GenoType® MTBDRsl assay (Hains, Lifesciences, Germany) is a new rapid

Cited by 29 publications

References 19 publications

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

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

Diagnostic Accuracy of a Molecular Drug Susceptibility Testing Method for the Antituberculosis Drug Ethambutol: a Systematic Review and Meta-Analysis

Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia

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