Treatment of Pulmonary Tuberculosis
Standard Treatment Regimen for Drug-Susceptible TB
For patients with pulmonary tuberculosis without HIV infection, initiate a 6-month regimen consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) given daily for 8 weeks (intensive phase), followed by isoniazid and rifampin for 18 weeks (continuation phase). 1, 2, 3
Intensive Phase (First 2 Months)
- Four-drug therapy: INH, RIF, PZA, and EMB administered daily for 56 doses over 8 weeks 1, 2
- Dosing for daily therapy:
- Ethambutol can be discontinued once drug susceptibility testing confirms the organism is susceptible to INH and RIF, typically after 2 months 1, 5
- Alternative dosing schedules include twice-weekly (after initial 2 weeks of daily therapy) or three-times-weekly throughout, but these require directly observed therapy (DOT) 1, 2
Continuation Phase (Months 3-6)
- Two-drug therapy: INH and RIF for 18 weeks (126 doses if daily, 36 doses if twice weekly) 1, 2
- Extended to 7 months (total 9 months) if: 1, 5
- Cavitary disease on chest X-ray AND positive sputum culture at 2 months
- Initial phase did not include pyrazinamide
- Patient received once-weekly INH/rifapentine with positive culture at 2 months
Critical Monitoring Points
- Sputum cultures at 2 months to assess treatment response and determine if continuation phase extension is needed 1, 5
- Drug susceptibility testing should be performed on all initial isolates to guide therapy 5, 3
- Directly observed therapy (DOT) is strongly recommended for all intermittent regimens and should be used whenever operationally feasible for daily regimens 1, 2, 5
Treatment for HIV Co-Infected Patients
For HIV-infected patients with pulmonary TB, use the same 6-month four-drug regimen, but substitute rifabutin for rifampin if the patient is taking protease inhibitors or NNRTIs, and extend treatment to 9 months for patients with cavitation, CD4 count <100 cells/mm³, or positive cultures at 2 months. 1, 2, 5
Key Modifications for HIV Co-Infection
Drug interactions with antiretroviral therapy:
- Rifabutin replaces rifampin when patients are on protease inhibitors (indinavir, nelfinavir, amprenavir) or NNRTIs to avoid critical drug interactions 1, 2
- Rifabutin dosing adjustments: 1
- Reduce daily dose from 300 mg to 150 mg when used with indinavir, nelfinavir, or amprenavir
- Increase dose from 300 mg to 450 mg when used with efavirenz
- Twice-weekly dose remains 300 mg regardless of concurrent antiretroviral therapy
- Never interrupt antiretroviral therapy to accommodate rifampin, as this increases mortality risk 1, 2
Additional requirements:
- Pyridoxine (vitamin B6) 25-50 mg daily must be given to all HIV-infected patients receiving isoniazid to prevent peripheral neuropathy 1, 2, 5
- Initiate antiretroviral therapy within 2-8 weeks of starting TB treatment, based on CD4 count 5
- Extended treatment duration (9 months minimum) for patients with delayed response, cavitation, or immunosuppression 1, 2
Monitoring intensification:
- Liver function tests should be monitored more frequently due to increased hepatotoxicity risk in HIV-infected patients 5
- CD4 counts and HIV viral load should be checked at least every 3 months 5
- Screen for malabsorption in advanced HIV disease, as this may require therapeutic drug monitoring to prevent treatment failure 3
Alternative Regimens When Rifamycins Cannot Be Used
If rifampin or rifabutin cannot be used due to drug interactions or intolerance, use a 9-month regimen of isoniazid, streptomycin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid, streptomycin, and pyrazinamide for 7 months. 1, 6
- This non-rifamycin regimen requires minimum 9 months duration (60 induction doses plus 60-90 continuation doses) 1
- Consider extending to 12 months for patients with delayed response to treatment 1
- This approach is particularly relevant when managing patients requiring high-dose corticosteroids (e.g., autoimmune conditions) where rifampin's CYP450 induction would reduce corticosteroid efficacy by 50% or more 6
Critical Pitfalls to Avoid
Never use rifampin with protease inhibitors or NNRTIs without switching to rifabutin, as this causes treatment failure of either HIV or TB. 2, 5
Never add a single drug to a failing regimen, as this creates acquired drug resistance—always add at least two drugs to which the organism is likely susceptible 2, 5
Never omit ethambutol in the initial phase unless drug susceptibility is confirmed and community isoniazid resistance is <4% 1, 2, 3
Never delay TB treatment to accommodate other medications, as TB treatment is the immediate priority for mortality reduction 2
Never rely on negative AFB smears alone to exclude TB diagnosis—culture and molecular testing (Xpert MTB/RIF) are essential 5
Never use standard corticosteroid doses with rifampin in patients requiring corticosteroids for other conditions—increase corticosteroid dose 2-3 times baseline to compensate for rifampin's enzyme induction 6
Never use rifapentine in HIV-infected patients, as safety and effectiveness have not been established in this population 1
Special Considerations
Extrapulmonary Tuberculosis
- Use the same 6-month regimen for most extrapulmonary TB (lymph nodes, pleural effusion, pericarditis) 5, 3
- Extend to 9-12 months for TB meningitis, miliary TB, and bone/joint TB in children 5, 3, 7
- Corticosteroids are beneficial for TB meningitis (to reduce neurologic sequelae) and TB pericarditis (to prevent cardiac constriction) 3
Pregnancy
- The same four-drug regimen is safe in pregnant women, including those with HIV co-infection 5, 3
- Streptomycin should be avoided in pregnancy due to ototoxicity risk 3