What tests confirm Multidrug-Resistant Tuberculosis (MDR TB)?

Confirming MDR-TB Diagnosis: Essential Tests and Approaches

The definitive diagnosis of MDR-TB requires both culture-based and molecular drug susceptibility testing (DST) that confirms resistance to at least isoniazid and rifampin. 1

Primary Diagnostic Methods

Initial Testing

• Rapid molecular DST should be the first-line approach for suspected MDR-TB cases 1, 2
  • GeneXpert MTB/RIF is the most widely validated rapid test that simultaneously detects M. tuberculosis and rifampin resistance within hours (sensitivity 95%, specificity 98%) 2, 3
  • Line probe assays (LPAs) can detect both rifampin and isoniazid resistance

Confirmatory Testing

• Culture-based DST remains the gold standard and must be performed to confirm molecular test results 1
  • Liquid culture systems provide faster results (10-14 days) than solid media (3-4 weeks) 1
  • Culture confirmation is essential even when molecular tests are positive 1

Testing Algorithm for MDR-TB Diagnosis

1. Collect appropriate respiratory specimens:

   • At least two sputum specimens for microscopy and one for rapid molecular testing 1
   • For children: induced sputum, gastric aspirates, or bronchoalveolar lavage if needed 1

2. Perform rapid molecular testing:

   • GeneXpert MTB/RIF or other WHO-recommended rapid molecular test on the first specimen 2
   • If rifampin resistance is detected, immediately collect additional samples for confirmatory testing

3. Conduct culture and conventional DST:

   • All specimens should undergo culture regardless of molecular test results 1
   • First-line DST must include at least isoniazid and rifampin 1
   • Second-line DST should be performed if rifampin resistance is detected to rule out XDR-TB 4

Special Considerations

High-Risk Populations

Rapid molecular DST is particularly important for patients who are 1:

• Previously treated for TB
• Born in or lived in countries with high MDR-TB prevalence (≥2%)
• Contacts of known MDR-TB patients
• HIV-infected

Pediatric MDR-TB Diagnosis

• More challenging due to paucibacillary nature of disease
• May require multiple specimen types (gastric aspirates, induced sputum)
• Regular monitoring with audiometry is essential if injectable agents are used 1

Pitfalls and Limitations

• False rifampin resistance results: Can occur with certain GeneXpert MTB/RIF versions - always confirm with culture-based DST 1
• Discordant results: When molecular and phenotypic tests disagree, sequencing can help resolve discrepancies 1
• Incomplete resistance profile: Rapid tests typically only detect rifampin and sometimes isoniazid resistance - full DST is needed for complete resistance profile 1
• Extrapulmonary specimens: Molecular tests have lower sensitivity in non-respiratory samples 1

Quality Assurance

• All laboratories performing TB diagnostics should participate in quality assurance programs 1
• Specimens should be processed according to standardized protocols to ensure reliable results 1
• Laboratories should be part of a network with referral capabilities for advanced testing 1

By following this systematic approach to MDR-TB diagnosis, clinicians can rapidly identify drug resistance and initiate appropriate treatment, which is crucial for improving patient outcomes and preventing further transmission of resistant strains.