Tuberculosis meningitis

Opinion statement

• Treatment of tuberculous meningitis should begin with an anti-tuberculous regimen of at least three drugs: isoniazid, pyrazinamide, and rifampin. Early in the course of therapy, ethambutol or streptomycin may be of some added benefit. If the local incidence of drug resistance to Mycobacterium tuberculosis is greater than 4%, or is unknown, then a fourth drug (ethambutol or streptomycin) should be added [1••, Class III].

• If the patient is from an area with organisms resistant to multiple drugs, or is likely to be infected with a multiply resistant organism for any reason, then the patient should be on enough drugs to insure that at least two active anti-tubercular drugs are included in the therapy. An expert should be consulted [1••, Class II]

• Length of therapy is not standardized. For sensitive organisms, a regimen of three drugs daily for 2 months, followed by two-drug therapy (isoniazid and rifampin) has been recommended. The American Thoracic Society (ATS) and the Centers for Disease Control (CDC) have recommended a minimum of 12 months of therapy for tuberculous meningitis [1••, Class III]. If cultures remain positive for extended periods, or signs or symptoms respond slowly, therapy should be extended to 18 months [2••, Class III; 3, Class III]. Patients with HIV also may need longer courses of therapy [1••, Class III].

• The severity of tuberculous meningitis can be classified based on a system devised by the British Medical Research Council. Stage I patients are fully conscious, rational, and do not have neurologic signs. Stage II patients are confused or have neurologic signs such as cranial nerve palsy or hemiparesis. Stage III patients are comatose or stuporous with more severe neurologic signs [4•]. Corticosteroids are recommended if the patient is mentally confused, has neurologic signs, or is comatose (Stages II and III). In patients with moderate disease (Stage II), corticosteroids appear to improve neurologic sequelae and survival. Dexamethasone 6 to 12 mg per day and prednisone 60 to 80 mg per day tapered over 4 to 8 weeks has been used. Symptoms of central nervous system (CNS) inflammation may recur if the corticosteroid taper is implemented too soon or too fast [4•, Class III].

• Steroids and diuretics such as furosemide and acetazolamide are sometimes used to treat hydrocephalus [5, Class III]. Ventriculoperitoneal or ventriculoatrial shunting may be required to relieve signs and symptoms of hydrocephalus [6, Class III; 7, Class III; 8, Class III].