GeneXpert MTB/RIF for Tuberculosis Diagnosis
Primary Recommendation
GeneXpert MTB/RIF should replace sputum smear microscopy as the initial diagnostic test for all patients with suspected pulmonary tuberculosis, regardless of HIV status or drug resistance risk, with specimens simultaneously sent for liquid culture and phenotypic drug susceptibility testing. 1
Diagnostic Performance
Pulmonary Tuberculosis Detection
GeneXpert demonstrates pooled sensitivity of 89% (85-92%) and specificity of 99% (98-99%) for pulmonary TB detection, representing a 23% increase in case detection compared to smear microscopy alone. 1
In AFB smear-positive patients, a negative GeneXpert result makes TB disease highly unlikely, with false-negative results occurring in only 4% of cases. 2
For smear-negative patients, GeneXpert maintains sensitivity of 79-90% depending on bacillary load, substantially outperforming microscopy which has highly variable and poor sensitivity. 2, 3
Immunocompromised Patients
In people living with HIV, GeneXpert sensitivity is 79% (70-86%), making it particularly valuable in this high-risk population where rapid diagnosis is critical. 1, 2
For severely ill or immunocompromised patients with strong clinical suspicion, initiate anti-tuberculosis treatment immediately even if initial GeneXpert is negative, as false-negatives occur more frequently in paucibacillary disease. 1, 2
Rifampicin Resistance Detection
Performance Characteristics
GeneXpert provides robust rifampicin resistance detection with pooled sensitivity of 96% and specificity of 98%, serving as an excellent surrogate marker for multidrug-resistant TB. 2, 4
Rifampicin resistance detected by GeneXpert indicates MDR-TB in approximately 90% of cases, requiring immediate referral to specialized MDR-TB management. 5, 6
Risk-Based Testing Strategy
Perform rapid molecular drug susceptibility testing for rifampicin on all patients who meet ANY of these criteria: 1
- Previous tuberculosis treatment history
- Born in or lived ≥1 year in a country with TB incidence ≥20 per 100,000 or MDR-TB prevalence ≥2%
- Known contact of MDR-TB patient
- HIV infection
Critical Limitation
- The positive predictive value for rifampicin resistance is lower in populations with low drug resistance prevalence, so all molecular resistance results must be confirmed by phenotypic drug susceptibility testing via liquid culture. 1, 5
Specimen Collection and Processing
Pulmonary TB
Collect at least 2 sputum specimens for microscopy and 1 for GeneXpert testing, with simultaneous submission for liquid culture. 1, 5
For patients unable to produce sputum, use sputum induction with bronchodilator, bronchoscopy with bronchoalveolar lavage, or gastric washings. 1
Extrapulmonary TB
GeneXpert sensitivity for extrapulmonary TB is 79-82% with specificity of 86%, lower than pulmonary specimens but still superior to smear microscopy. 4, 7
Submit all extrapulmonary specimens (pleural fluid, CSF, ascitic fluid, tissue biopsies) for simultaneous GeneXpert, culture, and histopathological examination in quality-assured laboratories. 1, 7
Pediatric Patients
For children unable to produce sputum, collect gastric aspirates on 3 consecutive mornings (yields 40-50% diagnostic confirmation overall, up to 90% in infants). 6
Alternative methods include sputum induction or nasopharyngeal aspiration (20-30% yield), with bronchoscopy reserved for complicated cases. 6
Management of Indeterminate Results
Immediate Actions
When GeneXpert returns indeterminate rifampicin resistance, immediately repeat GeneXpert on a new specimen, simultaneously send for liquid culture and phenotypic DST, and initiate standard four-drug first-line therapy (rifampicin, isoniazid, pyrazinamide, ethambutol) while awaiting confirmatory results. 5
Critical Pitfall to Avoid
Do NOT start MDR-TB treatment based on indeterminate results alone—this causes unnecessary toxicity without confirmed benefit. 5
Rapid molecular DST is an adjunct, not a replacement for culture-based DST, which remains the laboratory gold standard. 1, 5
Monitoring During Workup
Perform monthly sputum smear and culture while awaiting final DST results. 5
If sputum remains positive at 2 months, repeat molecular testing and comprehensive DST. 5
Clinical Decision-Making Algorithm
When GeneXpert is Positive for TB, Rifampicin-Sensitive
- Initiate standard four-drug first-line therapy immediately
- Await culture confirmation and full DST panel
- Monitor treatment response clinically and microbiologically
When GeneXpert is Positive for TB, Rifampicin-Resistant
- Assess patient's risk factors for MDR-TB (see criteria above) 1
- In high-risk patients, consider empiric MDR-TB treatment while awaiting phenotypic DST confirmation 5
- In low-risk patients with low pretest probability, start first-line therapy and await phenotypic DST confirmation due to lower positive predictive value 1, 5
- Refer immediately to physician with substantial MDR-TB management experience 5
When GeneXpert is Negative but Clinical Suspicion Remains High
- Do NOT rule out TB based on negative GeneXpert alone in severely ill, immunocompromised, or smear-negative patients 1, 2
- Initiate empiric anti-tuberculosis treatment if clinical evidence strongly suggests TB 1
- Avoid fluoroquinolones during diagnostic workup as they have anti-TB activity and may cause transient improvement, confounding diagnosis 1
- Await culture results (gold standard) before discontinuing treatment 1
Quality Assurance Requirements
Use only FDA-approved Xpert MTB/RIF assay in the United States, which is the only validated commercial test. 6
Ensure testing occurs in quality-assured laboratories with established proficiency and appropriate turnaround times. 1, 6
Meticulous attention to specimen collection and processing is essential, as technique significantly impacts diagnostic yield. 6
If using in-house molecular tests, they must be validated with analytical performance comparable to or better than commercial tests. 1