- TB is a systemic disease caused by M. tuberculosis.
- Most cases are the result of reactivation of prior infection, and persons at highest risk include those with HIV infection, silicosis, diabetes mellitus, chronic renal insufficiency, malignancy, malnutrition, and other forms of immunosuppression, especially therapy with tumor necrosis factor (TNF) antagonists like infliximab and etanercept.
- The prevalence of TB, particularly multidrug-resistant forms (MDR-TB), is increased among immigrants from Southeast Asia, Sub-Saharan Africa, the Indian subcontinent, and Central America. Extreme multidrug resistant TB (XDR-TB) is becoming increasingly prevalent in Sub-Saharan Africa.
- The most frequent clinical presentation is pulmonary disease.
- Extrapulmonary disease may present as cervical lymphadenitis, genitourinary disease, osteomyelitis, miliary dissemination, meningitis, peritonitis, or pericarditis.
- Positive fluorochrome or acid-fast bacteria (AFB) smears of sputum are presumptive evidence of active TB, although nontuberculous mycobacteria and some Nocardia species may give positive results with these techniques.
- Use of radiometric culture systems and species-specific DNA probes can provide results faster than traditional methods.
- Drug susceptibility testing should be performed on all initial isolates as well as on follow-up isolates from patients who do not respond to standard therapy.
- Treatment does not have to take place in a hospital setting, but hospitalization to initiate therapy provides an opportunity for intensive patient education.
- If a patient is hospitalized, proper isolation in a negative-pressure room is essential.
- The local health department should be notified of all cases of TB so that contacts can be identified and adherence to the regimen can be ensured by directly observed therapy.
- Chemotherapy: At least two drugs to which the organism is susceptible must be used because of the high frequency with which primary drug resistance to a single drug develops. Extended therapy is necessary because of the prolonged generation time of mycobacteria.
- Because adherence to multidrug regimens for prolonged periods is difficult, directly observed therapy should be used for all patients.
- Initial therapy of uncomplicated pulmonary TB should include four drugs unless the likelihood of drug resistance is very low (i.e., the rate of isoniazid [INH] resistance in the community is <4% or the patient has not received prior therapy for TB, has not been exposed to any contacts with drug-resistant TB, and is not from an area where drug-resistant TB is prevalent):
- INH (5 mg/kg; maximum, 300 mg PO daily),
- RIF (10 mg/kg; maximum, 600 mg PO daily),
- pyrazinamide (PZA, 15-30 mg/kg, maximum 2 g PO daily), and either ethambutol (EMB, 15-25 mg/kg PO daily) or streptomycin (15 mg/kg; maximum, 1.5 g IM daily) should be administered initially.
- If the isolate proves to be fully susceptible to INH and RIF, EMB (or streptomycin) can be dropped and INH, RIF, and PZA continued to finish 8 weeks, followed by 16 weeks of INH and RIF. Patients at high risk for relapse (cavitary pulmonary disease or positive TB cultures after 2 months of therapy) should be treated for 9 months.
- After at least 2 weeks of daily therapy, the drugs can be administered two or three times per week at adjusted doses. Pyridoxine (vitamin B6), 25-50 mg PO daily, should be considered for all patients who take INH to prevent neuropathy.
- Organisms that are resistant only to INH can be effectively treated with a 6-month regimen if a standard four-drug regimen consisting of INH, RIF, PZA, and EMB or streptomycin was started initially.
- When INH resistance is documented, the INH should be discontinued, and the remaining three drugs should be continued for the duration of therapy.
- Therapy for multidrug-resistant TB has been less well studied, and consultation with an expert in the treatment of TB should be considered.
- Extrapulmonary disease in adults can be treated in the same manner as pulmonary disease, with 6- to 9-month regimens. TB meningitis should be treated for 9-12 months.
- Glucocorticoid administration. In TB, the administration of glucocorticoids is controversial. Prednisone, 1 mg/kg PO daily initially, has been used in combination with antituberculous drugs for life-threatening complications such as meningitis and pericarditis.
- Monitoring response to therapy. Patients with pulmonary TB whose sputum AFB smears are positive before treatment should submit sputum for AFB smear and culture every 1-2 weeks until AFB smears become negative. Sputum should then be obtained monthly until two consecutive negative cultures are documented. Conversion of cultures from positive to negative is the most reliable indicator of a response to treatment. Continued symptoms or persistently positive AFB smears or cultures after 3 months of treatment should raise the suspicion of drug resistance or nonadherence and prompt referral to an expert in the treatment of TB.
- Monitoring for adverse reactions. Most patients should have a baseline laboratory evaluation at the start of therapy that includes hepatic enzymes, bilirubin, CBC, and serum creatinine. Routine laboratory monitoring for patients with normal baseline values is probably unnecessary except in patients with HIV, cases of alcohol consumption, in chronic liver disease, and in pregnant women. Monthly clinical evaluations with specific inquiries about symptoms of drug toxicity are essential. Patients who are taking EMB should be tested monthly for visual acuity and red-green color perception.