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Molecular Detection of Drug Resistance (MDDR)

Intended use Rapid detection of drug resistance in Mycobacterium tuberculosis isolates
Assay DNA sequencing will be performed using the ABI 3130xl.  Sequencing will be performed from PCR products amplified from genetic loci associated with resistance to first- and second-line anti-tuberculosis drug.  DNA sequencing was chosen as the platform due to its automation, high-throughput and potential for expansion (additional loci can be added to the panel).
Loci to be sequenced and associated drug resistance First-line MDDR to detect MDR-TB
  • rpoB (Rifampin)
  • inhA and katG (Isoniazid)

Second-line MDDR to detect XDR-TB

  • gyrA (Fluoroquinolones)
  • rrs (Kananmycin, Amikacin, Capreomycin)
  • eis (Kanamycin)
  • tlyA (Capreomycin)
  • pncA (Pyrazinamide)
  • embB(Ethambutol)

Performance
compared to conventional susceptibility testing
Drug Gene Sensitivity (%) Specificity (%)
RMP rpoB 96.1 97
INH inhA + katG 88.6 98.7
FQ

 gyrA

 82.2

 97
KAN rrs + eis 86.8 96.9
AMK rrs 87.9 99
CAP rrs + tlyA 44.6 85.9
PZA pncA 84.6 85.8
EMB embB 78.6 93.1
Limitations
  • Potential to identify mutations that do not confer phenotypic resistance
  • Not all genetic loci associated with resistance are known, therefore, a susceptible molecular result does not rule out resistance
Submission criteria Must meet one of the following criteria:
  • High Risk of RMP-R or MDR-TB (e.g. previous TB, MDR-TB contact, foreign born)
  • Known RMP-R
  • High profile patient (e.g. daycare worker, nurse)
  • Adverse reaction (e.g. RMP allergy)
  • Mixed or non-viable culture
  • Others may be accepted on case by case basis
Sample types accepted Isolates only (one per patient)
  • Solid Media (e.g. LJ or Middlebrook)
  • MGIT cultures
  • Bactec460 vials will not be accepted
Submission guidelines
  • Isolates must be shipped Monday-Thursday
  • Submit LB MDDR request form by email TBLab@cdc.gov
  • Wait for approval and further instructions
  • Submit isolate, attach DASH and MDDR request form
Conventional DST All isolates submitted for MDDR will also undergo conventional DST by the agar proportion method (PZA by MGIT 960)
Reporting
  • Interim Report: MDDR results
  • Final Report: MDDR and Conventional DST results with “conclusion”/”final interpretation”
References
  • S. Ramaswamy and J.M. Musser. Tubercle and Lung Disease. 79(1):3-29, 1998.
  • C. Maus et al. AAC. 49(8):3192-3197, 2005.
  • S. Feuerriegel et al. AAC. Epub, 2009.
  • M. Zaunbrecher et al., PNAS. 106(47):2004-9, 2009
  • P. Campbell  AAC. 55(5):2032-2041, 2011

MDDR Contact Information:

Centers for Disease Control and Prevention
Division of Tuberculosis Elimination
Laboratory Branch
1600 Clifton Road, NE, MS F08
Atlanta, GA 30333

Telephone: 404-639-2455
FAX: 404-639-5491
Email: TBLab@cdc.gov

 
Contact Us:
  • Centers for Disease Control and Prevention
    Division of Tuberculosis Elimination (DTBE)
    1600 Clifton Rd., NE
    MS E10
    Atlanta, GA 30333
  • 800-CDC-INFO
    (800-232-4636)
    TTY: (888) 232-6348
  • New Hours of Operation
    8am-8pm ET/Monday-Friday
    Closed Holidays
  • cdcinfo@cdc.gov
USA.gov: The U.S. Government's Official Web PortalDepartment of Health and Human Services
Centers for Disease Control and Prevention   1600 Clifton Rd. Atlanta, GA 30333, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348 - cdcinfo@cdc.gov
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