Molecular Detection of Drug Resistance (MDDR) for Mycobacterium tuberculosis complex

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Brief Description

Molecular-based antimicrobial susceptibility testing (AST) is a rapid DNA sequencing based platform aimed at the detection of genetic markers of drug resistance for Mycobacterium tuberculosis complex (MTBC). Results are available in hours as compared to weeks for conventional antimicrobial susceptibility testing.

Laboratory Unit

Tuberculosis

Methodology

Rapid molecular-based antimicrobial susceptibility testing using DNA pyrosequencing.

Specimen Collection

Molecular and growth-based susceptibility testing are automatically performed on MTBC isolated from each patient..

Storage/Transport

Submit isolates using the tuberculosis (TB) Category A carrier provided by the MSPHL in accordance with the Infectious Substance, Category A shipping guidelines.

Acceptable Specimen
Type(s)

Submit a slant (L-J, Middlebrook, or Mitchison) or liquid broth culture (MGIT, VersaTREK, or MP).

Mixed or non-viable MTBC organism is acceptable; however, growth-based AST may not be available.

Test Request Form(s)

Tuberculosis Test Request Form

Possible Results

No MTBC amplification detected

No mutation detected

rpoB mutation present (Ser531Leu) - resistance to rifampin

rpoB mutation present (Phe514Phe) - silent mutation; does not confer resistance to rifampin

katG mutation present (Ser315Thr), and no inhA or ahpC mutation present - resistance to isoniazid

No katG or ahpC mutation present, and inhA mutation present (C-15T) - low-level isoniazid resistance

ahpC mutation present (G-10A) - resistance to isoniazid

gyrA mutation present (Asp94Gly) - resistance to fluoroquinolones

rrs mutation present (A1401G) - resistance to second-line injectable drugs (amikacin, kanamycin, capreomycin)

The wild-type amino acid, codon number and mutant amino acid will be reported when a mutation is present. Examples listed above are of the most common mutations within Missouri. Novel mutations detected by pyrosequencing will be reported with referenced literature.

Reference Range

Mutation present or not detected by DNA sequencing in the following targeted regions associated with drug resistance.

IS6110 - M. tuberculosis complex confirmation

rpoB (RRDR) - Rifampin

katG (Ser315 Codon) - Isoniazid

inhA (Promoter) - Isoniazid

ahpC (Promoter) - Isoniazid

gyrA (QRDR) - Fluoroquinolones

rrs (1400 Region) - Second-line injectable drugs (Amikacin, Kanamycin, Capreomycin)

Unacceptable Conditions

No name or patient identifier on specimen
Specimen leaked during transport to the laboratory


Interfering Substances

N/A

Result Reported

24-48 hours

Results are reported the same day of receipt for known TB isolates

Fees

N/A

CPT Codes

87798

LOINC/SNOMED Codes

N/A

Additional Information

An isolate with mutations present confirming multidrug-resistant TB (MDR-TB) or extensively drug resistant TB (XDR-TB) will automatically be submitted to the CDC for confirmation and second-line antimicrobial susceptibility testing.

Testing will automatically be repeated, or upon request, on MTBC isolated from patients who has been on three months of antitubercular therapy to determine if the patient has developed resistance.

The Association of State and Territorial Health Officials (ASTHO) recognized the use of a universal laboratory screening test for multidrug-resistant tuberculosis (MDR-TB); resistance to rifampin and isoniazid. Reflex testing is beneficial, as it allow the most rapid detection of MDR and XDR-TB patients.