Model Performance Evaluation Program Report of Results: August 2021
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.
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)
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 .
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.
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.
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]) 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].
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 .
Table 1. Expected Growth-based Results for August 2021 Survey
|Isolate||RMP||INH||EMB||PZA||Second-line Drugs Resistances:|
|2021G||S||R||S||S||STR, OFL, CIP|
|2021H||S||R||S||S||OFL, CIP, ETA|
|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
¥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
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