The First Month Of A New Diagnostic Service For Molecular Detection Of MDR And XDR Tuberculosis

Driscoll, Jeffery A.; Lentz, Allison; Sikes, David; Hartline, Denise; Metchock, Beverly

doi:10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a2259

Cited by 4 publications

(4 citation statements)

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“…In September 2009, our laboratory at CDC began offering a new, Clinical Laboratory Improvement Amendments (CLIA)-compliant reference service: DNA sequencing of drug resistance-associated loci (8). Prior to implementation, to verify this molecular detection of drug resistance (MDDR) service, we sequenced all or part of nine loci in 314 M. tuberculosis complex isolates.…”

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confidence: 99%

Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

Campbell

Morlock

Sikes

et al. 2011

Antimicrob Agents Chemother

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335

351

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The emergence of multi-and extensively drug-resistant tuberculosis is a significant impediment to the control of this disease because treatment becomes more complex and costly. Reliable and timely drug susceptibility testing is critical to ensure that patients receive effective treatment and become noninfectious. Molecular methods can provide accurate and rapid drug susceptibility results. We used DNA sequencing to detect resistance to the first-line antituberculosis drugs isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) and the second-line drugs amikacin (AMK), capreomycin (CAP), kanamycin (KAN), ciprofloxacin (CIP), and ofloxacin (OFX). Nine loci were sequenced: rpoB (for resistance to RIF), katG and inhA (INH), pncA (PZA), embB (EMB), gyrA (CIP and OFX), and rrs, eis, and tlyA (KAN, AMK, and CAP). A total of 314 clinical Mycobacterium tuberculosis complex isolates representing a variety of antibiotic resistance patterns, genotypes, and geographical origins were analyzed. The molecular data were compared to the phenotypic data and the accuracy values were calculated. Sensitivity and specificity values for the first-line drug loci were 97.1% and 93.6% for rpoB, 85.4% and 100% for katG, 16.5% and 100% for inhA, 90.6% and 100% for katG and inhA together, 84.6% and 85.8% for pncA, and 78.6% and 93.1% for embB. The values for the second-line drugs were also calculated. The size and scope of this study, in numbers of loci and isolates examined, and the phenotypic diversity of those isolates support the use of DNA sequencing to detect drug resistance in the M. tuberculosis complex. Further, the results can be used to design diagnostic tests utilizing other mutation detection technologies.

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confidence: 99%

Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

Campbell

Morlock

Sikes

et al. 2011

Antimicrob Agents Chemother

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335

351

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“…CDC offers the molecular detection of drug resistance (MDDR) for mutations associated with resistance to RMP at the RMP resistance-determining region (RRDR) of the rpoB locus and with resistance to INH at the katG and inhA loci (2,3). Other loci that are examined are embB (EMB resistance), pncA (pyrazinamide resistance), gyrA (fluoroquinolone resistance), rrs (kanamycin, amikacin, and capreomycin resistance), tlyA (capreomycin resistance), and eis (promoter region mutations associated with kanamycin resistance) (2).…”

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Concordance between Molecular and Phenotypic Testing of Mycobacterium tuberculosis Complex Isolates for Resistance to Rifampin and Isoniazid in the United States

et al. 2014

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Multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis complex (MTBC) are defined by resistance to at least rifampin (RMP) and isoniazid (INH). Rapid and accurate detection of multidrug resistance is essential for effective treatment and interruption of disease transmission of tuberculosis (TB).T wo essential drugs for the first-line treatment of tuberculosis (TB) are rifampin (RMP) and isoniazid (INH). Isolates of Mycobacterium tuberculosis complex (MTBC) that are resistant to at least both these drugs are classified as multidrug resistant (MDR). Rapid and accurate detection of resistance to either RMP or INH is crucial for selection of treatment regimens and public health interventions. In 2012, the Centers for Disease Control and Prevention (CDC) reported 9,945 cases of TB in the United States (http://www.cdc.gov/tb/statistics/reports/2012/default.htm). For 7,188 of these cases, for which initial drug susceptibility to firstline antituberculosis drugs was reported, 660 (9.2%) were at least INH resistant, and 83 (1.2%) were MDR. The American Thoracic Society, CDC, and the Infectious Diseases Society of America have issued guidelines for treating INH-monoresistant TB (1). Early detection of RMP resistance, which correlates well with multidrug resistance, is critical for the initiation of effective second-line treatment regimens and interruption of disease transmission.CDC offers the molecular detection of drug resistance (MDDR) for mutations associated with resistance to RMP at the RMP resistance-determining region (RRDR) of the rpoB locus and with resistance to INH at the katG and inhA loci (2, 3). Other loci that are examined are embB (EMB resistance), pncA (pyrazinamide resistance), gyrA (fluoroquinolone resistance), rrs (kanamycin, amikacin, and capreomycin resistance), tlyA (capreomycin resistance), and eis (promoter region mutations associated with kanamycin resistance) (2). MDDR is available by request in coordination with state public health laboratories (PHL) for M. tuberculosis isolates and sediments meeting submission criteria (http://www.cdc.gov/tb/topic /laboratory/MDDRsubmissionform.pdf). Although molecular testing can rapidly detect mutations associated with drug resistance, it should complement, not supersede, conventional phenotypic drug susceptibility testing (DST) (4). Therefore, all submissions to MDDR undergo growth-based DST for a full panel of first-line and second-line drugs (4). Submitters receive a preliminary report with molecular test results and a final report upon completion of DST, with both the molecular and DST results and interpretive comments.In this study, we examined the concordances between molecular testing and DST for RMP and INH to determine the performance characteristics of CDC's MDDR service for rapid detection and confirmation of MDR TB. Through an electronic survey using a secure data collection instrument, we collected phenotypic DST results from state and local PHL for isolates submitted for testing at CDC. We examined the concordances between molecular ...

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“…The final report contains interpretive comments based on both molecular and growth-based results. CDC's MDDR service has been described previously [ 22 , 23 ].…”

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confidence: 99%

Molecular and Growth-Based Drug Susceptibility Testing ofMycobacterium tuberculosisComplex for Ethambutol Resistance in the United States

Yakrus

Driscoll

McAlister

et al. 2016

Tuberculosis Research and Treatment

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Ethambutol (EMB) is used as a part of drug regimens for treatment of tuberculosis (TB). Susceptibility of Mycobacterium tuberculosis complex (MTBC) isolates to EMB can be discerned by DNA sequencing to detect mutations in the embB gene associated with resistance. US Public Health Laboratories (PHL) primarily use growth-based drug susceptibility test (DST) methods to determine EMB resistance. The Centers for Disease Control and Prevention (CDC) provides a service for molecular detection of drug resistance (MDDR) by DNA sequencing and concurrent growth-based DST using agar proportion. PHL and CDC test results were compared for 211 MTBC samples submitted to CDC from September 2009 through February 2011. Concordance between growth-based DST results from PHL and CDC was 88.2%. A growth-based comparison of 39 samples, where an embB mutation associated with EMB resistance was detected, revealed a higher percentage of EMB resistance by CDC (84.6%) than by PHL (59.0%) which was significant (P value = 0.002). Discordance between all growth-based test results from PHL and CDC was also significant (P value = 0.003). Most discordance was linked to false susceptibility using the BACTEC™ MGIT™ 960 (MGIT) growth-based system. Our analysis supports coalescing growth-based and molecular results for an informed interpretation of potential EMB resistance.

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The First Month Of A New Diagnostic Service For Molecular Detection Of MDR And XDR Tuberculosis

Cited by 4 publications

References 0 publications

Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

Concordance between Molecular and Phenotypic Testing of Mycobacterium tuberculosis Complex Isolates for Resistance to Rifampin and Isoniazid in the United States

Molecular and Growth-Based Drug Susceptibility Testing ofMycobacterium tuberculosisComplex for Ethambutol Resistance in the United States

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