What is the recommended workup and treatment for tuberculosis (TB)?

Tuberculosis Workup and Treatment

The recommended workup for tuberculosis (TB) includes sputum examination with molecular testing, chest radiography, and drug susceptibility testing, followed by a standard 6-month treatment regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, then isoniazid and rifampin for 4 additional months for drug-susceptible TB. 1

Diagnostic Workup

Initial Assessment

• Obtain three sputum specimens for:
  • Acid-fast bacilli (AFB) smear microscopy
  • Mycobacterial culture
  • Molecular testing (nucleic acid amplification test)
• Chest radiography (essential even if sputum is negative)
• Drug susceptibility testing on initial positive culture
• HIV testing for all TB patients

Laboratory Tests

• Complete blood count
• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase)
• Renal function tests (creatinine)
• Platelet count
• Hepatitis B and C testing for patients with risk factors

Special Situations

• For suspected extrapulmonary TB: appropriate specimens from affected sites
• For children or patients unable to produce sputum: consider gastric aspirates, induced sputum, or bronchoalveolar lavage
• For suspected drug-resistant TB: molecular testing for rifampin resistance

Treatment Regimens

Drug-Susceptible Pulmonary TB

1. Initial Phase (2 months):

   • Isoniazid (5 mg/kg/day, max 300 mg)
   • Rifampin (10 mg/kg/day, max 600 mg)
   • Pyrazinamide (15-30 mg/kg/day)
   • Ethambutol (15-20 mg/kg/day)

2. Continuation Phase (4 months):

   • Isoniazid and rifampin

Culture-Negative Pulmonary TB

• For smear-negative, culture-negative TB with clinical/radiographic evidence:
  • 4-month regimen may be adequate (2 months HRZE followed by 2 months HR) 1
  • For HIV-infected patients: minimum 6-month treatment 1

Extrapulmonary TB

• Most forms: 6-month standard regimen
• TB meningitis: 9-12 months
• Bone/joint TB: 9-12 months
• Consider adjunctive corticosteroids for TB pericarditis and meningitis 1

Special Populations

Children

• Similar regimen to adults
• Ethambutol can be used safely at 15-20 mg/kg/day even in young children 1
• Directly observed therapy (DOT) always recommended

Pregnant Women

• Avoid streptomycin (risk of congenital deafness)
• Pyrazinamide generally not recommended due to insufficient teratogenicity data
• Initial regimen: isoniazid, rifampin, and ethambutol 2

HIV Co-infection

• Same drugs but may require longer treatment duration
• Careful monitoring for drug interactions with antiretrovirals
• Consider therapeutic drug monitoring

Monitoring During Treatment

Clinical Monitoring

• Monthly clinical evaluations for treatment response and adverse effects
• Sputum smear and culture at 2 months to assess response
• If smear-positive at 3 months, evaluate for treatment failure or drug resistance 1

Laboratory Monitoring

• Regular liver function tests for patients with:
  • Pre-existing liver disease
  • HIV infection
  • Regular alcohol use
  • Pregnancy/postpartum
• Visual acuity and color discrimination testing for patients on ethambutol

Drug-Resistant TB Management

Multidrug-Resistant TB (MDR-TB)

• Requires at least 18-24 months of therapy
• Treatment should be individualized based on susceptibility testing
• Consultation with TB expert recommended 1
• At least two new drugs to which the organism is susceptible should be added 1

Common Pitfalls and Caveats

1. Failure to rule out active TB before starting latent TB treatment

   • Always obtain chest radiography and appropriate specimens before initiating treatment

2. Inadequate initial regimen

   • Use four drugs initially due to potential isoniazid resistance unless susceptibility is known

3. Poor adherence monitoring

   • Directly observed therapy (DOT) recommended for all patients to ensure adherence

4. Premature discontinuation of therapy

   • Complete the full course even if symptoms resolve quickly

5. Inadequate monitoring for drug toxicity

   • Monitor for hepatotoxicity, especially in high-risk patients
   • Consider pyridoxine (vitamin B6) supplementation for patients on isoniazid

6. Failure to adjust therapy based on susceptibility results

   • Modify regimen promptly when resistance is detected

7. Inadequate contact investigation

   • Report all TB cases promptly to public health authorities for contact tracing 1

By following this comprehensive approach to TB diagnosis and treatment, clinicians can optimize outcomes for patients while preventing disease transmission in the community.