Useful For
Suggests clinical disorders or settings where the test may be helpful
Susceptibility testing of Mycobacterium tuberculosis complex isolates growing in pure culture against pyrazinamide
This test is not useful for Mycobacterium bovis and Myocobacterium bovis bacille Calmette-Guerin (BCG) isolates as they are intrinsically resistant to pyrazinamide.
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id |
Reporting Name |
Available Separately |
Always Performed |
| MTBVP |
Mtb PZA Confirmation, pnc A Sequence |
No, (Bill Only)
|
No |
Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.
| Test Id |
Reporting Name |
Available Separately |
Always Performed |
| STVP |
Susceptibility, Mtb Complex, PZA |
No, (Bill Only)
|
Yes |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If resistance to pyrazinamide is detected, the reflex sequencing test or confirmation of resistance will be performed at an additional charge.
If the broth microdilution test is unable to be performed (eg, due to reagent shortages, failure of the isolate to grow in the test medium), the reflex sequencing test will be performed at an additional charge.
Method Name
A short description of the method used to perform the test
Broth Dilution at Critical Drug Concentrations
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Yes
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Susceptibility, Mtb Complex, PZA
Aliases
Lists additional common names for a test, as an aid in searching
Acid-Fast Bacilli (AFB)
AFB (Acid-Fast Bacilli)
Antibiotic Susceptibility
Antimicrobial Susceptibility, Mycobacterium tuberculosis
Bacillus, Acid-Fast
MTB (Mycobacterium tuberculosis)
Mycobacteria Antimicrobial Susceptibility (MIC) (Minimum Inhibitory Concentration)
Mycobacterium tuberculosis (MTB)
Susceptibility Testing
Susceptibility, Mycobacterium tuberculosis
TB (Tuberculosis)
Tubercle Bacilli: Mycobacterium tuberculosis
Tuberculosis (TB)
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If resistance to pyrazinamide is detected, the reflex sequencing test or confirmation of resistance will be performed at an additional charge.
If the broth microdilution test is unable to be performed (eg, due to reagent shortages, failure of the isolate to grow in the test medium), the reflex sequencing test will be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
To test for first-line agents, isoniazid, rifampin and ethambutol, order TB1LN / Antimicrobial Susceptibility, Mycobacterium tuberculosis Complex, First Line, Varies.
Isolates identified as Mycobacterium bovis and Myocobacterium bovis bacille Calmette-Guerin (BCG) will not be accepted as they are intrinsically resistant to pyrazinamide.
Additional Testing Requirements
If organism identification is not provided, CTB / Mycobacteria and Nocardia Culture, Varies or CTBID / Culture Referred for Identification, Mycobacterium and Nocardia, Varies must also be ordered and will be charged separately.
Shipping Instructions
1. See Infectious Specimen Shipping Guidelines
2. Place specimen in a large infectious container (T146) and label as an etiologic agent/infectious substance.
Necessary Information
Specimen source and suspected organism identification are required.
ORDER QUESTIONS AND ANSWERS
| Question ID |
Description |
Answers |
| Q00M0074 |
Specimen source (Required) and Organism Identification (Required unless concurrent identification test is ordered) |
|
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Specimen Type: Organism
Supplies: Infectious Container, Large (T146)
Container/Tube: Middlebrook 7H10 agar slant
Specimen Volume: Isolate
Collection Instructions: Organism must be in pure culture, actively growing.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
If not ordering electronically, complete, print, and send a Microbiology Test Request (T244) with the specimen.
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
Agar plate Reject
| Specimen Type |
Temperature |
Time |
Special Container |
|
Varies |
Ambient (preferred) |
|
|
|
Refrigerated |
|
Useful For
Suggests clinical disorders or settings where the test may be helpful
Susceptibility testing of Mycobacterium tuberculosis complex isolates growing in pure culture against pyrazinamide
This test is not useful for Mycobacterium bovis and Myocobacterium bovis bacille Calmette-Guerin (BCG) isolates as they are intrinsically resistant to pyrazinamide.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If resistance to pyrazinamide is detected, the reflex sequencing test or confirmation of resistance will be performed at an additional charge.
If the broth microdilution test is unable to be performed (eg, due to reagent shortages, failure of the isolate to grow in the test medium), the reflex sequencing test will be performed at an additional charge.
Initial treatment regimens for Mycobacterium tuberculosis complex often include isoniazid, rifampin, ethambutol, and pyrazinamide (PZA). Susceptibility testing of M tuberculosis complex isolates against these antimycobacterial agents is a key component of patient management.
The Clinical and Laboratory Standards Institute provides consensus protocols for the methods, antimycobacterial agents, and critical concentrations of each agent to be tested to permit standardized interpretation of M tuberculosis complex susceptibility test results.
This test uses a US Food and Drug Administration cleared commercial system for rapid broth susceptibility testing of M tuberculosis complex against PZA. The literature indicates that broth testing of PZA can, at times, produce falsely resistant results, so resistance to PZA by the broth method is automatically confirmed by pncA DNA sequencing. Variants in the pncA gene and upstream promoter region have been reported to account for the majority (70%-97%) of PZA-resistant isolates. However, 3% to 30% of PZA-resistant isolates do not have a corresponding pncA variant and other genes (eg, rpsA) may also play a role.
A separate test is available for testing of the other primary agents (isoniazid, rifampin and ethambutol). If desired, this must be ordered separately; TB1LN / Antimicrobial Susceptibility, Mycobacterium tuberculosis Complex, First Line, Varies.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Results are reported as susceptible or resistant.
Interpretation
Provides information to assist in interpretation of the test results
Mycobacterium tuberculosis complex isolates are reported as susceptible or resistant to pyrazinamide at the critical concentration.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
For isolates determined to be resistant by the broth method, confirmatory testing using pncA DNA sequencing is automatically performed and the presence or absence of pncA variations associated with pyrazinamide resistance is reported. Some variants associated with pyrazinamide resistance may occur outside of the pncA promoter and gene region and may therefore not be confirmed by DNA sequencing of this target. Presence of a pncA mutation associated with resistance confirms the broth susceptibility testing results. Absence of a pncA mutation does not rule out possible resistance.
Susceptibility testing should be performed on pure culture isolates of Mycobacterium tuberculosis complex.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Nahid P, Mase SR, Migliori GB, et al. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline [published correction appears in Am J Respir Crit Care Med. 2020 Feb 15;201(4):500-501
2. Dormandy J, Somoskovi A, Kreiswirth BN, Driscoll JR, Ashkin D, Salfinger M. Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains. Chest. 2007;131(2):497-501. doi:10.1378/chest.06-1899
3. Chedore P, Bertucci L, Wolfe J. Potential for erroneous results indicating resistance when using the BACTEC MGIT 960 system for testing susceptibility of mycobacterium tuberculosis to Pyrazinamide. J Clin Microbiol 2010;48(1):300-301
4. Campbell PJ, Morlock GP, Sikes RD, et al. Molecular resistance 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):2032-2041
5. Shi W, Zhang X, Jiang X, et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011;333(6049):1630-1632
6. Clinical and Laboratory Standards Institute (CLSI). Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes. 3rd ed. CLSI standard M24. CLSI; 2018
7. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes. 2nd ed. CLSI supplement M24S. CLSI; 2023
8. Espasa M, Salvado M, Vicente E, et al. Evaluation of the versaTREK system compared to the Bactec MGIT 960 system for first-line drug susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2012;50:488-491
9. Somoskovi A, Dormandy J, Parson LM, et al. Sequencing of the pncA gene in members of the Mycobacterium tuberculosis complex has important diagnostic applications: Identification of a species-specific pncA mutation in "Mycobacterium canettii" and the reliable and rapid predictor of pyrazinamide resistance. Confirmation of pyrazinamide resistance is done using Sanger dideoxy sequencing of approximately 700bp of the pncA gene and promoter region. J Clin Microbiol. 2007;45(2):595-599
10. Jureen P, Werngren J, Toro JC, Hoffner S: Pyrazinamide resistance and pncA gene mutations in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2008;52(5):1852-1854
Method Description
Describes how the test is performed and provides a method-specific reference
This test is based on presence or absence of growth of an Mycobacterium tuberculosis complex isolate in broth cultures in the presence of critical concentrations of the antimycobacterial drug pyrazinamide. One of two FDA-cleared platforms (BD MGIT 960 or the VersaTREK) will be used. (Brown-Elliott, BA, Cirillo DM, Musser KA, Rowlinson M-C. Susceptibility Test Methods: Mycobacteria, Nocardia, and Other Actinomycetes. In: Carroll KC, Pfaller MA, eds. Manual of Clinical Microbiology, 13th Edition. ASM Press, 2023)
The BACTEC MGIT 960 platform measures fluorescence in a Mycobacterial Growth Indicator Tube (MGIT) containing an M tuberculosis complex isolate in the presence of a critical concentrations of pyrazinamide (Package insert: BACTEC MGIT 960 SIRE Kit, BD Diagnostics, 9/2019)
The VersaTrek platform inside bottles containing M tuberculosis complex isolates in the presence of a critical concentration of the antimycobacterial PZA. (Package insert: VersaTREK Mycobacteria Detection and Susceptibility Testing system, TREK Diagnostics, 04/2014)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
No
Monday through Sunday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
10 to 21 days
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
1 year
Rochester
Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
87188-Susceptibility, Mycobacterium tuberculosis Complex, Pyrazinamide
87153-Mtb PZA Confirmation, pncA Sequencing (if appropriate)
| Test Id |
Test Order Name |
Order LOINC Value
|
| TBPZA |
Susceptibility, Mtb Complex, PZA |
56026-8 |
| Result Id |
Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
| TBPZA |
Susceptibility, Mtb Complex, PZA |
56026-8 |