Model Performance Evaluation Program Report of Results: February 2022

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MPEP February 2022 [PDF – 912 KB]

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 February 2022.

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

Primary Classification

This report contains DST results submitted to CDC by survey participants at 63 laboratories in 33 states.

The participants were asked to indicate the primary classification of their laboratory (Figure 1).

Figure 1. Primary Classification of Participating Laboratories, February 2022

Figure 1. Primary Classification of Participating Laboratories, February 2022

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Annual Number of MTBC Drug Susceptibility Tests Performed

The number of MTBC isolates tested for drug susceptibility by the 63 participants in 2021 (excluding isolates used for quality control) is shown in Figure 2. In 2021, the counts ranged from 0 to 812 tests. Participants at 24 (38%) 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].

Figure 2. Distribution of the Annual Volume of MTBC Isolates Tested for Drug Susceptibility by Participants in Previous Calendar Year (n=63)

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 performed by participating laboratories for this panel of MTBC isolates are displayed in Figure 3. Of participating laboratories, 37 (59%) reported results for only one method, 22 (35%) reported two methods, and 4 (6%) noted three susceptibility methods.

Figure 3. MTBC Drug Susceptibility Test Method Performed by Participants (n=93)

Figure 3. MTBC Drug Susceptibility Test Method Performed by Participants (n=93)

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Molecular methods reported by participants are shown in Figure 4. The method performed most frequently (50%) was targeted DNA sequencing, including pyrosequencing and Sanger sequencing. Three (22%) laboratories reported use of the Cepheid Xpert® MTB/RIF assay, two (14%) reported results for line probe assays, Bruker Genotype MTBDRplus and MTBDRsl, and two (14%) reported results from whole genome sequencing.

Figure 4. Molecular Method Reported (n=14)

Figure 4. Molecular Method Reported (n=14)

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Antituberculosis Drugs Tested by Participants

The number of participating laboratories that reported testing each antituberculosis drug in the February 2022 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 6- or 9-month four-drug RIPE TB treatment regimen used for many patients. Laboratories may consider the addition of fluoroquinolones to their testing panel as CDC recommends susceptibility testing for fluoroquinolones (e.g., moxifloxacin) with use of the 4-month rifapentine-moxifloxacin treatment regimen; RMP results may be used as a proxy for rifapentine [9].

All participants reported results for three of the first-line drugs (RMP, INH, and EMB) and 59 (94%) 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. Twenty laboratories tested at least one fluoroquinolone.

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) [10, 11]. Twenty laboratories reported second-line drug results other than streptomycin. Five (22%) of these laboratories 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 the former classification of XDR TB. Three laboratories tested at least one fluoroquinolone and either bedaquiline or linezolid to define the WHO’s revised XDR TB definition.

Figure 5. Antituberculosis Drugs Tested by Growth-based Method by Participants

Figure 5. Antituberculosis Drugs Tested by Growth-based Method 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 February 2022 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 whole genome sequencing are listed in Table 2[5].

Table 1. Expected Growth-based Results for February 2022 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:
2022A S S S S*
2022B S* S S S
2022C S R S S OFL, CIP, ETA
2022D S* S S S
2022E S R R* S STR*, 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 February 2022 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 embB pncA gyrA ethA
2022A Glu37Val
2022B His445Leu*
(His526Leu)†
2022C C-15T Ala90Val
2022D Asp435Tyr*
(Asp516Tyr)†
2022E Ser315Thr Met306Val Partial deletion

¥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
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