Multidrug-resistant tuberculosis: rapid detection of resistance to rifampin and high or low levels of isoniazid in clinical specimens and isolates

Vijdea, R.; Stegger, Marc; Sosnovskaja, Anaida; Andersen, Åse Bengård; Thomsen, Vibeke Østergaard; Bang, Didi

doi:10.1007/s10096-008-0548-9

Cited by 33 publications

(39 citation statements)

References 25 publications

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“…This test is useful due to its accuracy and specificity, as well as its short turnaround time and ease of use. Previous studies have demonstrated that the GenoType MTBDRplus test had outstanding performance: 91.7% to 100% accuracy in detecting RIF resistance, 34.6% to 94.6% accuracy in detecting INH resistance, and 92% to 100% accuracy in detecting MDR (1,4,6,10,15,21). In comparison, the GenoType MTBDRplus test identified 95.4% of RIF-resistant isolates, 81.8% of INH-resistant isolates, and 78.5% of MDR isolates in our study.…”

Section: Discussionmentioning

confidence: 38%

“…The World Health Organization and partners have endorsed the use of the molecular test GenoType MTBDRplus (Hain Lifescience GmbH, Nehren, Germany) for rapid detection of high-risk MDR-TB cases, even directly from certain clinical specimens (1,4,6,10,15,21). The GenoType MTBDRplus test is a PCR-based amplification and reverse blotting assay that employs specific probes hybridized to nitrocellulose strips to detect RIF and INH resistance.…”

mentioning

confidence: 99%

“…Likewise, the distribution of M. tuberculosis isolates differs in different geographic regions (5,11). The GenoType MTBDRplus test has been assessed in Europe (6,10,15,21), South Africa (4), and the Caribbean (1), but not in the Asia-Pacific region, where there is a high prevalence of Beijing family M. tuberculosis isolates. Here we report the performance of the revised GenoType MTBDRplus test compared to that of DNA sequencing using a culture-based phenotypic DST, which is considered the gold standard for routine clinical practice.…”

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confidence: 99%

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Performance Assessment of the GenoType MTBDR plus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis

Huang¹,

Chen²,

Kuo³

et al. 2009

J Clin Microbiol

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To facilitate the management of multidrug-resistant (MDR) tuberculosis, two nucleic acid sequence-based methods, the GenoType MTBDRplus test and DNA sequencing, were assessed for the rapid detection of drug-resistant Mycobacterium tuberculosis for the first time in the Asia-Pacific region. The performances of these two assays in detecting the presence of rifampin (rifampicin) (RIF) and isoniazid (INH) resistanceassociated mutations in the rpoB, katG, inhA regulatory region, inhA, and oxyR-ahpC genes were compared to that of a conventional agar proportion drug susceptibility test. A total of 242 MDR and 30 pansusceptible M. tuberculosis isolates were evaluated in this study. The sensitivities obtained for RIF-resistant detection by the GenoType MTBDRplus test and by resistance gene sequencing were 95.5% and 97.9%, respectively. The sensitivities for INH resistance detection by the GenoType MTBDRplus test and by resistance gene sequencing were 81.8% and 93.4%, respectively. Together, the sensitivity for MDR tuberculosis detection was 78.5% with the GenoType MTBDRplus test and 91.3% by resistance gene sequencing. The specificity for RIF resistance, INH resistance, and MDR detection was 100% by both methods. The GenoType MTBDRplus test has the advantage of a short turnaround time for drug-resistant M. tuberculosis detection. Overall, the two assays performed equally well in detecting RIF resistance (P ‫؍‬ 0.13). However, DNA sequencing demonstrated superior performance in detecting INH resistance (P < 0.001) and MDR tuberculosis (P < 0.001). We suggest that new alleles of INH resistance genes should be evaluated to improve the sensitivity of the GenoType MTBDRplus test, especially for different geographic areas with genetically diverse M. tuberculosis strains.

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Section: Discussionmentioning

confidence: 38%

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confidence: 99%

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confidence: 99%

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Performance Assessment of the GenoType MTBDR plus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis

Huang¹,

Chen²,

Kuo³

et al. 2009

J Clin Microbiol

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“…The line probe assays (LPA) GenoType MTBDRplus (Hain Lifescience, Nehren, Germany) and INNO-LiPA Rif.TB (InnoGenetics, Ghent, Belgium) were carried out as previously described (7)(8)(9). With these kits, PCR of rpoB is followed by hybridization of mutants to a membrane strip.…”

Section: P Atients With Tuberculosis (Tb) That Harbor Drug-susceptiblementioning

confidence: 99%

Rifampin Heteroresistance in Mycobacterium tuberculosis Cultures as Detected by Phenotypic and Genotypic Drug Susceptibility Test Methods

et al. 2013

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Tuberculosis patients may harbor both drug-susceptible and -resistant bacteria, i.e., heteroresistance. We used mixtures of rifampin-resistant and -susceptible Mycobacterium tuberculosis strains to simulate heteroresistance in patient samples. Molecular tests can be used for earlier discovery of multidrug resistance (MDR), but the sensitivity to detect heteroresistance is unknown. Conventional phenotypic drug susceptibility testing was the most sensitive, whereas two line probe assays and sequencing were unable to detect the clinically important 1% resistant bacteria. Patients with tuberculosis (TB) that harbor drug-susceptible Mycobacterium tuberculosis strains may also have a small proportion of drug-resistant bacteria that develops spontaneously during replication, normally at a rate of 10 Ϫ8 to 10 Ϫ9 mutations/ cell division (1). For rifampin (Rif) resistance, mutations are almost exclusively found in a single gene, rpoB (2). Conventional drug susceptibility testing (DST) aims to determine if 1% or more of the bacterial population in clinical specimens is drug resistant (3, 4). In this study, cultures that contain both susceptible and at least 1% resistant bacteria are defined as heteroresistant. Heteroresistance is thought to be an early stage in the development of drug-resistant TB in a patient. In such cases, failing to detect resistance may lead to insufficient treatment and treatment failure. As a consequence, spread of resistant bacteria may occur in the future (5). The prevalence of heteroresistance is unknown and is presumably dependent on the local resistance epidemiology. Findings of heteroresistance are accidental, and simple methods for the detection are needed (6).In recent years, a number of genotypic methods have become available for rapid detection of mutations that may confer resistance. Molecular tests have been recommended for use worldwide, with the objective of earlier discovery of multidrug resistance (MDR) (http://www.who.int/tb/features_archive/policy _statement.pdf). These assays are important for the global scaling up of detection of MDR-TB. However, little is known of the sensitivity of these methods to detect resistance in heteroresistant specimens. The aim of the present study was to evaluate the ability of different DST methods to detect Rif resistance when heteroresistance is present.Two freeze-dried strains each of the spoligo families Haarlem and Beijing were obtained from the WHO Tropical Disease Research (TDR) TB Strain Bank. The Haarlem strain TB-TDR-063 was susceptible, and TB-TDR-165 was Rif resistant with the rpoB H526Y mutation. The Beijing strain TB-TDR-077 was susceptible, and TB-TDR-068 was Rif resistant with the rpoB S531L mutation. The susceptible strains from both families had wild-type (WT) DNA in rpoB. The strains were subcultured in Dubos with 0.045% Tween 80 (SSI Diagnostika, Hilleroed, Denmark) with 1 mg/ml Rif (BD, Franklin Lakes, NJ) diluted in water for the resistant strains. After 2 weeks of incubation at 37°C, the bacterial concentrations in liquid medi...

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“…[32][33][34][35][36][37][38][39][40][41][42] Conceptually similar to the INNO-Lipa Rif.tb assay, the MTBDRplus assay has been reported to have a diagnostic sensitivity of approximately 94% for detecting M tuberculosis DNA in smear-positive respiratory specimens. 33 It is of interest that most clinical evaluations of this device have focused on its use for susceptibility testing, not detection of M tuberculosis, so the performance characteristics for the latter use are less well defined.…”

Section: Line Probe Assaysmentioning

confidence: 99%

Rapid Diagnosis of Mycobacterium tuberculosis Infection and Drug Susceptibility Testing

Wilson

2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.—The global control of tuberculosis remains a challenge from the standpoint of diagnosis, detection of drug resistance, and treatment. This is an area of special concern to the health of women and children, particularly in regions of the world with high infant mortality rates and where women have limited access to health care. Objective.—Because treatment can only be initiated when infection is detected, and is guided by the results of antimicrobial susceptibility testing, there recently has been a marked increase in the development and testing of novel assays designed to detect Mycobacterium tuberculosis complex, with or without simultaneous detection of resistance to isoniazid and/or rifampin. Both nonmolecular and molecular assays have been developed. This review will summarize the current knowledge about the use of rapid tests to detect M tuberculosis and drug resistance. Data Sources.—Review of the most recent World Health Organization Global Tuberculosis Report, as well as selected publications in the primary research literature, meta-analyses, and review articles. Conclusions.—To a large extent, nonmolecular methods are refinements or modifications of conventional methods, with the primary goal of providing more rapid test results. In contrast, molecular methods use novel technologies to detect the presence of M tuberculosis complex and genes conferring drug resistance. Evaluations of molecular assays have generally shown that these assays are of variable sensitivity for detecting the presence of M tuberculosis complex, and in particular are insensitive when used with smear-negative specimens. As a group, molecular assays have been shown to be of high sensitivity for detecting resistance to rifampin, but of variable sensitivity for detecting resistance to isoniazid.

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Multidrug-resistant tuberculosis: rapid detection of resistance to rifampin and high or low levels of isoniazid in clinical specimens and isolates

Cited by 33 publications

References 25 publications

Performance Assessment of the GenoType MTBDR plus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis

Performance Assessment of the GenoType MTBDR plus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis

Rifampin Heteroresistance in Mycobacterium tuberculosis Cultures as Detected by Phenotypic and Genotypic Drug Susceptibility Test Methods

Rapid Diagnosis of Mycobacterium tuberculosis Infection and Drug Susceptibility Testing

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