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Test ID: TBPZA Susceptibility, Mycobacterium tuberculosis Complex, Pyrazinamide, Varies


Reporting Name

Susceptibility, Mtb Complex, PZA

Useful For

Susceptibility testing of Mycobacterium tuberculosis complex isolates growing in pure culture against pyrazinamide


Confirming M tuberculosis complex resistance to pyrazinamide

Clinical Information

Primary treatment regimens for Mycobacterium tuberculosis complex often include isoniazid, rifampin, ethambutol, and pyrazinamide (PZA). Susceptibility testing of each M tuberculosis complex isolate against these first-line antimycobacterial agents is a key component of patient management.


The Clinical and Laboratory Standards Institute (CLSI) provides consensus protocols for the methods, antimycobacterial agents, and critical concentrations of each agent to be tested in order to permit standardized interpretation of M tuberculosis complex susceptibility test results. Current recommendations indicate that laboratories should use a rapid broth method in order to obtain M tuberculosis complex susceptibility data as quickly as possible to help guide patient management. According to the CLSI, resistance can be confirmed by another method or by another laboratory at the discretion of the testing laboratory.


This test uses an FDA-cleared commercial system for rapid broth susceptibility testing of M tuberculosis complex against PZA. Since the literature indicates that broth testing of PZA can, at times, produce falsely resistant results, resistance to PZA by the broth method is automatically confirmed by pncA DNA sequencing. The pncA gene of M tuberculosis complex is responsible for activation of the prodrug PZA and hence PZA activity. Variations 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 first-line agents (isoniazid, rifampin and ethambutol). If desired, this must be ordered separately; TB1LN / Antimicrobial Susceptibility, Mycobacterium tuberculosis Complex, First Line, Varies.


Mycobacterium tuberculosis complex isolates are reported as susceptible or resistant to pyrazinamide at the critical concentration.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MTBVP Mtb PZA Confirmation, pnc A Sequence No, (Bill Only) No

Testing Algorithm

When this test is ordered the additional test will always be performed at an additional charge.

If resistance to pyrazinamide is detected, the reflex test for confirmation of resistance will be performed at an additional charge.

Report Available

10 to 21 days

Day(s) Performed

Monday through Sunday

Clinical Reference

1. Blumberg HM, Burman WJ, Chaisson RE, et al: American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003;167(4):603-662

2. Woods GL, Lin S-Y G, Desmond EP: Susceptibility test methods: Mycobacteria, Nocardia and other Actinomycetes. In Manual of Clinical Microbiology.10th edition. Edited by J Versalovic, KC Carroll, G Funke, et al. ASM Press, 2011, pp 1215-1238

3. Dormandy J, Somoskovi A, Kreiswirth BN, et al: 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;131:497-501

4. 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 Jan;48(1):300-301

5. 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;55:2032-2041

6. Shi W, Zhang X, Jiang X, et al: Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 2011;333:1630-1632

7. CLSI, Susceptibility Testing of Mycobacteria, Nocardiae, and Other Actinomycetes; Approved Standard, Third edition. CLSI document M24. Clinical and Laboratory Standards Institute, 2018

8. CLSI. Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia species, and Other Aerobic Actinomycetes. First edition. CLSI supplement M62. Clinical and Laboratory Standards Institute; 2018

9. LaBombardi VJ: Comparison of the ESP and BACTEC Systems for testing susceptibilities of Mycobacterium tuberculosis complex isolates to pyrazinamide. J Clin Microbiol 2002;40:2238-2239

10. 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

11. 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;45:595-599

12. Jureen P, Werngren J, Toro JC, Hoffner S: Pyrazinamide resistance and pncA gene mutations in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2008;52:1852-1854

Method Name

Broth Dilution at Critical Drug Concentrations

Specimen Type


Ordering Guidance

To test for first-line agents, isoniazid, rifampin and ethambutol, order TB1LN / Antimicrobial Susceptibility, Mycobacterium tuberculosis Complex, First Line, Varies

Additional Testing Requirements

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 unless identification of organism is provided.

Shipping Instructions

1. See Infectious Specimen Shipping Guidelines in Special Instructions.

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.

Specimen Required

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.

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)

Reference Values

Results are reported as susceptible or resistant.

Test Classification

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.

CPT Code Information

87188-Susceptibility, Mycobacterium tuberculosis Complex, Pyrazinamide

87153-Mtb PZA Confirmation, pncA Sequencing (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TBPZA Susceptibility, Mtb Complex, PZA 56026-8


Result ID Test Result Name Result LOINC Value
TBPZA Susceptibility, Mtb Complex, PZA 56026-8

Additional Tests

Test ID Reporting Name Available Separately Always Performed
STVP Susceptibility, Mtb Complex, PZA No, (Bill Only) Yes


If not ordering electronically, complete, print, and send a Microbiology Test Request (T244) with the specimen.

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