Treatment of Tuberculosis
The standard treatment for drug-susceptible tuberculosis is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase), with a cure rate exceeding 95% when patients complete the full course of therapy. 1
Standard Treatment Regimen for Drug-Susceptible TB
Initial (Intensive) Phase - First 2 Months:
- Isoniazid (INH)
- Rifampin (RIF)
- Pyrazinamide (PZA)
- Ethambutol (EMB) - until drug susceptibility is confirmed
Continuation Phase - Next 4 Months:
- Isoniazid (INH)
- Rifampin (RIF)
This regimen is recommended by the American Thoracic Society, Centers for Disease Control and Prevention (CDC), and the Infectious Diseases Society of America 2, 1.
Administration and Monitoring
- Administration schedule: Daily dosing is preferred for both intensive and continuation phases 2
- Directly Observed Therapy (DOT) is strongly recommended to ensure adherence and prevent development of drug resistance 2, 1
- Pyridoxine (vitamin B6, 25-50 mg/day) should be given with INH to patients at risk of neuropathy (pregnant women, breastfeeding infants, HIV patients, diabetics, alcoholics, malnourished individuals, patients with chronic renal failure, and older adults) 2, 1
- Monitoring: Monthly clinical evaluations and sputum cultures at 2 months are crucial 1
- Baseline testing: Liver function tests and visual acuity/color discrimination testing (for ethambutol) 1
Special Situations
Drug-Resistant TB
Isoniazid-Resistant TB:
- Add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 2
- Pyrazinamide may be shortened to 2 months in selected situations (non-cavitary disease, lower burden disease, or toxicity) 2
Multidrug-Resistant TB (MDR-TB):
- Treatment should include at least 5 effective drugs in the intensive phase and 4 drugs in the continuation phase 2, 1
- Treatment duration should be 15-21 months after culture conversion 1
- Expert consultation is strongly recommended 2
Extrapulmonary TB
Special Populations
HIV Co-infection:
- Same regimen as non-HIV patients but requires careful monitoring 1
- If CD4 count <100/μL, continuation phase should consist of daily or three times weekly INH and RIF 1
Children:
- Standard 6-month regimen with INH and RIF supplemented with PZA during the first 2 months 2
- EMB should be included unless the strain is known to be susceptible to INH and RIF 1
Pregnancy:
- Standard regimen without PZA is generally recommended in the US due to inadequate teratogenicity data 1
Common Pitfalls and Caveats
Failure to ensure adherence: Non-adherence is the main reason for treatment failure and development of drug-resistant strains 2. Always use DOT when possible.
Inadequate initial regimen: If local INH resistance rates exceed 4%, include EMB in the initial regimen until drug susceptibility is confirmed 1.
Failure to monitor for adverse effects:
Missing drug interactions: Rifampin is a potent enzyme inducer that can enhance metabolism of many medications including hormones and vitamin D 3
Delayed recognition of treatment failure: Reevaluate patients who are smear-positive at 3 months for possible non-adherence or drug-resistant infection 2
Failure to report cases: Each case of TB should be promptly reported to local public health authorities to allow contact investigations and monitoring 2
By following these evidence-based recommendations, tuberculosis can be effectively treated with high cure rates while minimizing the development of drug resistance.