Performance of Tuberculosis Drug Susceptibility Testing in U.S. Laboratories from 1994 to 2008

Angra, Pawan; Taylor, Thomas H.; Iademarco, Michael F.; Metchock, Beverly; Astles, J. Rex; Ridderhof, John C.

doi:10.1128/jcm.06479-11

Cited by 30 publications

(23 citation statements)

References 10 publications

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“…This recommendation is supported by a recent study published by the U.S. Centers for Disease Control and Prevention (CDC), based on results of a proficiency testing program in which cultures with known susceptibility or resistance were sent by the CDC to participating laboratories over a 15-year period (26). This study concluded that the ethambutol testing with MGIT is not equivalent to the critical concentrations used for the agar proportion methods or Bactec 460.…”

Section: Discussionsupporting

confidence: 57%

Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

et al. 2013

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fIn an effort to update and clarify policies on tuberculosis drug susceptibility testing (DST), the World Health Organization (WHO) commissioned a systematic review evaluating WHO-endorsed diagnostic tests. We report the results of this systematic review and meta-analysis of the diagnostic accuracy and reproducibility of phenotypic DST for first-line and second-line antituberculosis drugs. This review provides support for recommended critical concentrations for isoniazid and rifampin in commercial broth-based systems. Further studies are needed to evaluate critical concentrations for ethambutol and streptomycin that accurately detect susceptibility to these drugs. Evidence is limited on the performance of DST for pyrazinamide and second-line drugs.T he global epidemic of drug-resistant tuberculosis (DR-TB), particularly multidrug-resistant TB (MDR-TB, defined as resistance to at least isoniazid and rifampin), is one of the most serious problems facing TB care and control efforts. In their most recent worldwide survey, the World Health Organization (WHO) documented the highest rates of MDR-TB ever reported (1). Effective management of drug-resistant TB relies on multiple components, including detection, treatment, prevention, surveillance, and continuous program evaluation (2). Expanding the capacity to diagnose cases of drug-resistant TB is a priority for global TB control, requiring clear policies on the use of diagnostic tests and strengthened laboratories in which testing can be safely and effectively carried out (3).Conventional phenotypic drug susceptibility testing (DST) using the proportion method (PM) on solid media has been well studied for isoniazid and rifampin, with a general consensus achieved regarding methodology, critical concentrations, and expected performance (4). However, the diagnostic accuracy and reproducibility of DST for other first-line and second-line drugs are inadequate (5). DST for second-line anti-TB drugs has not been standardized internationally, which is reflected in the wide variability of practices among supranational reference laboratories, underscoring the need for standardization of the methods and interpretive criteria for second-line DST (4, 6). Further complicating the lack of consensus is the increasing number of different DST methods that are available. In 2008, the WHO Stop TB Department published interim laboratory policy guidance for DST of second-line anti-TB drugs (4). Guideline recommendations for a specific DST method should ideally be based on the diagnostic test accuracy, reproducibility, ease of use, cost, and rapidity of result availability.In an attempt to address gaps in the evidence base, WHO initiated an update to the 2008 interim guidelines with an expanded scope to include DST for all first-line and second-line drugs. As part of the update, we conducted a systematic review to determine the diagnostic accuracy and reproducibility of WHO-endorsed phenotypic DST methods and commercial genotypic DST methods for first-line and second-line anti-TB drugs. Whi...

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Section: Discussionsupporting

confidence: 57%

Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

et al. 2013

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“…In addition, in a proficiency program conducted by the U.S. Centers for Disease Control and Prevention in which cultures of known ethambutol susceptibility or resistance status were sent to participating laboratories over a 15-year period, there were substantial differences in performance between the 7H10 APM and the liquid culture MGIT method (critical concentration of 5 g/ml for each method). Specifically, MGIT detected as resistant only 48.3% of strains with expected ethambutol resistance, leading the authors to conclude that re-evaluation of ethambutol critical concentrations is warranted (19). Notably, in our study, using the liquid MYCOTB method, the direction of discordance (driven mostly by isolates categorized as susceptible by MYCOTB and resistant by APM) was the same as that observed in the CDC program.…”

Section: Figsupporting

confidence: 47%

“…Ethambutol phenotypic DST is well-known to be challenging, with low interlaboratory agreement (18,19). There are several issues that warrant consideration.…”

Section: Figmentioning

confidence: 99%

Sensititre MYCOTB MIC Plate for Testing Mycobacterium tuberculosis Susceptibility to First- and Second-Line Drugs

Lee

Armstrong

Ssengooba

et al. 2014

Antimicrob Agents Chemother

100

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f For Mycobacterium tuberculosis, phenotypic methods for drug susceptibility testing of second-line drugs are poorly standardized and technically challenging. The Sensititre MYCOTB MIC plate (MYCOTB) is a microtiter plate containing lyophilized antibiotics and configured for determination of MICs to first-and second-line antituberculosis drugs. To evaluate the performance of MYCOTB for M. tuberculosis drug susceptibility testing using the Middlebrook 7H10 agar proportion method (APM) as the comparator, we conducted a two-site study using archived M. tuberculosis isolates from Uganda and the Republic of Korea. Thawed isolates were subcultured, and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, and 21; APM results were read at 21 days. A total of 222 isolates provided results on both platforms. By APM, 106/222 (47.7%) of isolates were resistant to at least isoniazid and rifampin. Agreement between MYCOTB and APM with respect to susceptibility or resistance was >92% for 7 of 12 drugs when a strict definition was used and >96% for 10 of 12 drugs when agreement was defined by allowing a ؎ one-well range of dilutions around the APM critical concentration. For ethambutol, agreement was 80% to 81%. For moxifloxacin, agreement was 83% to 85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91% to 96%. For MYCOTB, the median time to plate interpretation was 10 days and interreader agreement was >95% for all drugs. MYCOTB provided reliable results for M. tuberculosis susceptibility testing of first-and second-line drugs except ethambutol, and results were available sooner than those determined by APM.T he emergence and spread of drug-resistant strains of Mycobacterium tuberculosis comprise a serious threat to tuberculosis (TB) control (1, 2). Knowledge of M. tuberculosis drug susceptibility is important in optimizing individual patient management and TB control in populations. Genotypic methods have the potential for a very short time to results, but to date, the knowledge of the full spectrum of genetic loci and mutations associated with resistance to many antituberculosis drugs is incomplete (3,4,5,6,7). Phenotypic methods therefore remain important. The reference phenotypic method-the indirect agar proportion method (APM) using Middlebrook solid media-is qualitative and based on drug critical concentrations. Limitations of the APM and related methods include lack of standardization and in some cases the need for in-laboratory preparation of drug stocks and agar plates, which can be a source of variability over time and between laboratories. Critical concentrations are based on historical epidemiological data and for some drugs are not well-aligned with achievable drug serum concentrations or accurate in predicting clinical failure (8,9,10). Studies on molecular drug resistance mechanisms in M. tuberculosis have shown that, at least for some antibiotics, different mutations are associated with different MICs, furthe...

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“…Discordant results were obtained for some isolates containing an Asp516Tyr mutation in rpoB which has been previously reported as associated with low-level RMP resistance and discordant test results with phenotypic DST methods (5,6). The widely used Bactec MGIT liquid culture system is more prone than solid media to miss low-level RMP resistance conferred by mutations at specific codons (7,8). Our molecular and phenotypic results for 285 isolates revealed that six isolates possessed an Asp516Tyr mutation, of which four were found to be RMP susceptible by phenotypic DST (data not shown).…”

Section: Discussionmentioning

confidence: 76%

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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Performance of Tuberculosis Drug Susceptibility Testing in U.S. Laboratories from 1994 to 2008

Cited by 30 publications

References 10 publications

Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

Sensititre MYCOTB MIC Plate for Testing Mycobacterium tuberculosis Susceptibility to First- and Second-Line Drugs

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

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