What are the recommended laboratory tests and treatment for tuberculosis (TB)?

Tuberculosis Laboratory Workup and Treatment

The essential laboratory tests for tuberculosis diagnosis include acid-fast bacilli (AFB) microscopy, nucleic acid amplification testing (NAAT), and both liquid and solid mycobacterial cultures, followed by drug susceptibility testing, with treatment consisting of a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. 1, 2

Diagnostic Laboratory Testing

Initial Testing

• Obtain three sputum specimens, preferably early morning samples on separate days, for AFB microscopy, culture, and drug susceptibility testing 1
• AFB microscopy should be completed within 24 hours of specimen collection to assess infectiousness and guide initial management 2
• Nucleic acid amplification testing (NAAT) should be performed on the initial respiratory specimen to rapidly identify M. tuberculosis complex 2
• NAAT results should be available within 48 hours of specimen collection 2
• In AFB smear-positive patients, a negative NAAT makes TB disease unlikely; in smear-negative patients with intermediate to high suspicion, a positive NAAT can be used as presumptive evidence of TB 2

Culture and Identification

• Both liquid and solid mycobacterial cultures should be performed on every specimen 2
• Liquid cultures typically yield results in 10-14 days, while solid cultures take 3-4 weeks 2
• Culture remains the gold standard for laboratory confirmation of TB and is required for isolating bacteria for drug susceptibility testing 2
• Identification of M. tuberculosis complex should be performed according to standard guidelines 2

Special Considerations

• For patients unable to produce sputum, consider sputum induction with hypertonic saline or bronchoscopy under appropriate infection control measures 1, 3
• Induced sputum testing has been shown to be more cost-effective than bronchoscopy, with a diagnostic yield of up to 96% compared to 52% for bronchoscopy 3
• For extrapulmonary TB, appropriate specimens from suspected sites should be obtained for microscopy, NAAT, culture, and histopathological examination 2

Treatment Protocol

Standard Regimen for Drug-Susceptible TB

• Initial phase: Isoniazid, rifampin, pyrazinamide, and ethambutol daily for 2 months 1, 4, 5
• Continuation phase: Isoniazid and rifampin daily for 4 months 1, 5, 6
• The total treatment duration is 6 months for most cases of drug-susceptible pulmonary TB 7, 8

Dosing Guidelines

• Isoniazid: 5 mg/kg (up to 300 mg) daily in a single dose; or 15 mg/kg (up to 900 mg) 2-3 times weekly 5
• Rifampin: Dosing according to FDA guidelines 6
• Pyrazinamide: Dosing according to CDC and American Thoracic Society recommendations 7
• Ethambutol: Added to initial regimen until sensitivity to isoniazid and rifampin is demonstrated 5

Treatment Modifications

• For culture-negative pulmonary TB, a 4-month regimen may be adequate after the initial 2-month four-drug regimen 4
• Extended treatment duration is recommended for cavitary pulmonary TB with positive cultures after 2 months of treatment 4
• For extrapulmonary TB, the basic principles of pulmonary TB treatment apply, though some forms (military TB, bone/joint TB, and TB meningitis) may require 9-12 months of therapy 5

Monitoring During Treatment

• Collect sputum specimens monthly until two consecutive specimens are culture-negative 1, 4
• Perform monthly clinical evaluations to identify possible adverse effects and assess adherence 1, 4
• Baseline laboratory testing (liver function tests) is indicated for HIV-infected persons, pregnant women, persons with history of liver disease, regular alcohol users, and persons at risk for chronic liver disease 4
• Drug susceptibility tests should be repeated if sputum specimens remain culture-positive after 3 months of treatment or if cultures revert to positive after initial conversion to negative 4

Common Pitfalls and Caveats

• Single-drug therapy should never be initiated as this can lead to development of drug resistance 4
• A single drug should not be added to a failing regimen as this can lead to resistance to the added drug 4
• NAAT testing should not be ordered routinely when clinical suspicion of TB is low, as the positive predictive value is <50% in such cases 2
• A single negative NAAT test result should not be used as a definitive result to exclude TB, especially when clinical suspicion is moderate to high 2
• Currently available NAAT tests are not sufficiently sensitive (detecting only 50-80% of AFB smear-negative, culture-positive pulmonary TB cases) to exclude TB in AFB smear-negative patients 2
• Patients should avoid alcohol and hepatotoxic medications while taking TB treatment to reduce the risk of liver toxicity 6