Model Performance Evaluation Program Report of Results: August 2021

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MPEP August 2021 pdf icon[PDF – 1 MB]

The purpose of this report is to present results of the U.S. Centers for Disease Control and Prevention (CDC) Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis complex (MTBC) drug susceptibility testing survey sent to participants in August 2021.

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Descriptive Information about Participant Laboratories
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Isolate Narratives and Tables
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Expected Drug-Susceptibility Test Results Tables
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References
Descriptive Information about Participant Laboratories

Primary Classification

This report contains DST results submitted to CDC by survey participants at 68 laboratories in 34 states.

The participants were asked to indicate the primary classification of their laboratory (Figure 1). MPEP participants self-classified as:

  • 49 (72%): Public health laboratory (e.g., local, county, state)
  • 9 (13%): Hospital laboratory
  • 7 (10%): Independent/Reference laboratory (non-hospital based)
  • 2 (3%): Federal government laboratory
  • 1 (2%): Other (Medical Manufacturing Company)
Primary Classification of Participating Laboratories, August 2021

Figure 1. Primary Classification of Participating Laboratories, August 2021

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Annual Number of MTBC Drug Susceptibility Tests Performed

The number of MTBC isolates tested for drug susceptibility by the 68 participants in 2020 (excluding isolates used for quality control) is shown in Figure 2. In 2020, the counts ranged from 0 to 782 tests. Participants at 29 (42%) laboratories reported testing 50 or fewer DST isolates per year. Laboratories with low MTBC DST volumes are encouraged to consider referral of testing because of concerns about maintaining proficiency [8].

Distribution of the Annual Volume of MTBC Isolates Tested for Drug Susceptibility by Participants in Previous Calendar Year

Figure 2. Distribution of the Annual Volume of MTBC Isolates Tested for Drug Susceptibility by Participants in Previous Calendar Year (n=68)

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MTBC DST Methods Used by Participants

The DST methods that were used by participating laboratories for this panel of MTBC isolates are displayed in Figure 3. Of participating laboratories, 43 (63%) reported results for only one method, 21 (31%) reported two methods, and 4 (6%) noted three susceptibility methods.

MTBC Drug Susceptibility Test Method Used by Participants

Figure 3. MTBC Drug Susceptibility Test Method Used by Participants (n=97)

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Molecular methods reported by participants are shown in Figure 4. The method used most frequently by six laboratories (55%) was targeted DNA sequencing, including pyrosequencing and Sanger sequencing. Two (18%) laboratories reported use of the Cepheid Xpert MTB/RIF assay, two (18%) reported results for line probe assays, Bruker Genotype MTBDRplus and MTBDRsl, and one (9%) reported results from whole genome sequencing.

Molecular Method Reported

Figure 4. Molecular Method Reported (n=11)

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Antituberculosis Drugs Tested by Participants

The number of participating laboratories that reported testing each antituberculosis drug in the August 2021 survey is presented in Figure 5. CLSI recommends testing a full panel of first-line drugs (rifampin [RMP], isoniazid [INH], ethambutol [EMB] and pyrazinamide [PZA])[1] because it represents a combination of tests that provides the clinician with comprehensive information related to the four-drug antituberculosis therapy currently recommended for most patients. All participants reported results for three of the first-line drugs (RMP, INH, and EMB) and 63 (93%) also reported results for PZA by growth-based DST methods. One laboratory performs molecular testing for PZA via sequencing of pncA, in place of growth-based DST.

For 21 laboratories reporting second-line drug results (with the exception of streptomycin), five (22%) tested all three second-line injectable drugs (amikacin, kanamycin, and capreomycin) and at least one fluoroquinolone (ofloxacin, ciprofloxacin, levofloxacin, or moxifloxacin) needed to confidently define XDR TB. CDC has adopted a new hybrid definition of XDR that includes both the former classification (i.e., MDR with resistance to second-line injectable plus fluoroquinolone) or the revised WHO definition (i.e., MDR plus resistance to fluoroquinolone and either bedaquiline or linezolid) [9, 10].

Antituberculosis Drugs Tested by Participants

Figure 5. Antituberculosis Drugs Tested by Participants

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Expected Drug Susceptibility Testing Results

Anticipated growth-based and molecular results for the panel of MTBC isolates sent to participants in August 2021 are shown in the tables below. Although CDC recommends broth-based methods for routine first-line DST of MTBC isolates, the results obtained by the reference agar proportion method (except for pyrazinamide, in which MGIT was performed) are shown in Table 1. Molecular results obtained by DNA sequencing are listed in Table 2 [5].

Table 1. Expected Growth-based Results for August 2021 Survey
Note—S=susceptible, R=resistant

Table 1. Expected Growth-based Results for September 2020 Survey
Isolate RMP INH EMB PZA Second-line Drugs Resistances:
2021F S S S S OFL, CIP
2021G S R S S STR, OFL, CIP
2021H S R S S OFL, CIP, ETA
2021I S S S S* OFL, CIP
2021J S R S S OFL, CIP, ETA

*80% consensus for a single categorical result for this drug of either susceptible or resistant was not achieved for this isolate among participating laboratories.

Table 2. Expected Molecular Results (Mutations Detected in Loci Associated with Resistance) for August 2021 Survey
Note—Empty cell=No mutation detected

Table 2. Expected Molecular Results (Mutations Detected in Loci Associated with Resistance) for February 2020 Survey
Isolate rpoB¥ katG inhA fabG1 gyrA
2021F Ala90Val
2021G Asp94Asn Asp94Gly
2021H Arg447Arg*
(Arg528Arg)†		 Leu203Leu Asp94Asn
2021I Ser91Pro
2021J C-15T Ala90Val

¥Mutation is listed using both the M. tuberculosis and E.coli numbering system [6, 7]
*M. tuberculosis numbering system used
†E. coli numbering system used

References
  1. CLSI, Susceptibility Testing of Mycobacteria, Nocardiae spp., and Other Aerobic Actinomycetes, in 3rd Ed. CLSI Standard M24. 2018, Clinical and Laboratory Standards Institute: Wayne, PA.
  2. CLSI, Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes, in 1st Ed. CLSI supplement M62. 2018, Clinical and Laboratory Standards Institute: Wayne, PA.
  3. World Health Organization, Technical Report on critical concentrations for drug susceptibility testing of isoniazid and the rifamycins (rifampicin, rifabutin and rifapentine). 2021: Geneva.
  4. World Health Organization, Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. 2018: Geneva.
  5. Campbell, P.J., et al., Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2011. 55(5): p. 2032-41.
  6. Andre, E., et al., Consensus numbering system for the rifampicin resistance-associated rpoB gene mutations in pathogenic mycobacteria. Clin Microbiol Infect, 2017. 23(3): p. 167-172.
  7. APHL, Issues in Mycobacterium tuberculosis complex (MTBC) Drug Susceptibility Testing: Rifampin (RIF), in APHL Issues in Brief: Infectious Diseases. 2019, Association of Public Health Laboratories: Washington, D.C.
  8. APHL, TB Drug Susceptibility Testing Expert Panel Meeting Summary Report. 2007, Association of Public Health Laboratories: Washington, D.C.
  9. World Health Organization, Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis, 27-29 October 2020. 2021, World Health Organization: Geneva.
  10. CDC Division of Tuberculosis Elimination, Dear Colleague Letter: Surveillance definitions for extensively drug resistant (XDR) and pre-XDR tuberculosis. 2022.
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  12. Carr W, K.E., Starks A, Goswami N, Allen L, Winston C, Interim Guidance: 4-Month Rifapentine-Moxifloxacin Regimen for the Treatment of Drug-Susceptible Pulmonary Tuberculosis—United States, 2022. MMWR Morb Mortal Wkly Rep, 2022. 71(8): p. 285-289.
  13. Chen, T.C., et al., Fluoroquinolones are associated with delayed treatment and resistance in tuberculosis: a systematic review and meta-analysis. Int J Infect Dis, 2011. 15(3): p. e211-6.
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  19. Kam, K.M., et al., Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin susceptibility. Microb Drug Resist, 2006. 12(1): p. 7-11.
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  26. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. 2021, World Health Organization: Geneva.
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Page last reviewed: May 9, 2022
Content source: Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention