Duration of Therapy for Tubercular Meningitis
Duration of Therapy for Tubercular Meningitis
What is the ideal duration of therapy for tubercular meningitis (TBM), TBM with tuberculoma, and cases of multiple intracranial tuberculoma (without evidence of TBM)?
B.K. Bajaj, MD, DM
Meningitis and intracranial tuberculoma are types of tuberculosis (TB) infection of the central nervous system (CNS). These types of infections are seen in regions where the incidence of tuberculosis is high and there is a prevalence of dissemination after primary TB infection. TB meningitis can also develop as an extrapulmonary consequence of reactivation tuberculosis. The pathogenesis of CNS involvement with tuberculosis begins with the seeding of the brain and meninges with tubercular bacilli during the bacillemia of a primary infection or reactivation of TB infection from another location in the body. Meningitis occurs when a tubercle ruptures into the subarachnoid space and the tubercular protein induces a hypersensitivity reaction that causes a prominent inflammatory reaction. The inflammatory response involves the cranial nerves and blood vessels with resultant thrombosis and infarction of brain. Additionally, hydrocephalus may develop because the inflammatory response impedes the circulation of cerebrospinal fluid (CSF). In the United States, TB meningitis causes about 1% of TB cases and the fatality rate ranges between 15% and 40%.
Tuberculomas develop from tubercles, which seeded the brain tissue during bacillemia during the primary infection or reactivation. Tuberculomas can be solitary or multiple and will appear as nodules or mass lesions on imaging. Patients with tuberculomas may present with focal neurologic symptoms corresponding to the area of the brain involved. Tuberculomas within the brain may present without evidence of meningeal involvement. Patients also can suffer from both intracranial tuberculoma and meningitis.
Treatment of CNS tuberculosis should begin as soon as possible when clinically suspected because patient outcome is improved when therapy is begun in the early stage of disease. For all types of CNS tuberculosis, treatment should begin with a combination of bactericidal drugs that penetrate into the CSF. The first line of therapy should include isoniazid (INH), rifampin, and pyrazinamide, all of which are bactericidal and achieve effective levels in the CSF. Pyrazinamide is given with INH and rifampin during the first 2 months of therapy, and then is stopped. A fourth drug should be used during the first 2 months of therapy when INH drug resistance is a concern. Drug resistance is a concern if the region has more than a 4% INH resistance rate, if the patient has received prior antituberculosis therapy, or if the patient has been exposed to a resistant case. Ethambutol or streptomycin are the medications recommended as the fourth agent. Ethambutol has moderate CSF penetration and streptomycin has poor penetration, so it has been given as a combination of intramuscular and intrathecal delivery.
The optimal duration of therapy for CNS tuberculosis has not been determined in a randomized, prospective, controlled trial. The present recommendations are based on clinical experience and have been published by the American Thoracic Society and the Centers of Disease Control and Prevention. Treatment for tuberculous meningitis, intracranial tuberculoma, or tuberculoma with meningitis should be given for 12 months when the tuberculosis strain is sensitive to the antibiotics. Treatment should be lengthened to 18 months if the patient does not receive pyrazinamide during the first 2 months of therapy. If a patient has a multidrug-resistant strain of CNS tuberculosis, therapy is often extended to 24 months. It is also recommended that patients with active tuberculosis have directly observed therapy to insure compliance, reduce the development of a resistant organism, and monitor clinical response.
What is the ideal duration of therapy for tubercular meningitis (TBM), TBM with tuberculoma, and cases of multiple intracranial tuberculoma (without evidence of TBM)?
B.K. Bajaj, MD, DM
Meningitis and intracranial tuberculoma are types of tuberculosis (TB) infection of the central nervous system (CNS). These types of infections are seen in regions where the incidence of tuberculosis is high and there is a prevalence of dissemination after primary TB infection. TB meningitis can also develop as an extrapulmonary consequence of reactivation tuberculosis. The pathogenesis of CNS involvement with tuberculosis begins with the seeding of the brain and meninges with tubercular bacilli during the bacillemia of a primary infection or reactivation of TB infection from another location in the body. Meningitis occurs when a tubercle ruptures into the subarachnoid space and the tubercular protein induces a hypersensitivity reaction that causes a prominent inflammatory reaction. The inflammatory response involves the cranial nerves and blood vessels with resultant thrombosis and infarction of brain. Additionally, hydrocephalus may develop because the inflammatory response impedes the circulation of cerebrospinal fluid (CSF). In the United States, TB meningitis causes about 1% of TB cases and the fatality rate ranges between 15% and 40%.
Tuberculomas develop from tubercles, which seeded the brain tissue during bacillemia during the primary infection or reactivation. Tuberculomas can be solitary or multiple and will appear as nodules or mass lesions on imaging. Patients with tuberculomas may present with focal neurologic symptoms corresponding to the area of the brain involved. Tuberculomas within the brain may present without evidence of meningeal involvement. Patients also can suffer from both intracranial tuberculoma and meningitis.
Treatment of CNS tuberculosis should begin as soon as possible when clinically suspected because patient outcome is improved when therapy is begun in the early stage of disease. For all types of CNS tuberculosis, treatment should begin with a combination of bactericidal drugs that penetrate into the CSF. The first line of therapy should include isoniazid (INH), rifampin, and pyrazinamide, all of which are bactericidal and achieve effective levels in the CSF. Pyrazinamide is given with INH and rifampin during the first 2 months of therapy, and then is stopped. A fourth drug should be used during the first 2 months of therapy when INH drug resistance is a concern. Drug resistance is a concern if the region has more than a 4% INH resistance rate, if the patient has received prior antituberculosis therapy, or if the patient has been exposed to a resistant case. Ethambutol or streptomycin are the medications recommended as the fourth agent. Ethambutol has moderate CSF penetration and streptomycin has poor penetration, so it has been given as a combination of intramuscular and intrathecal delivery.
The optimal duration of therapy for CNS tuberculosis has not been determined in a randomized, prospective, controlled trial. The present recommendations are based on clinical experience and have been published by the American Thoracic Society and the Centers of Disease Control and Prevention. Treatment for tuberculous meningitis, intracranial tuberculoma, or tuberculoma with meningitis should be given for 12 months when the tuberculosis strain is sensitive to the antibiotics. Treatment should be lengthened to 18 months if the patient does not receive pyrazinamide during the first 2 months of therapy. If a patient has a multidrug-resistant strain of CNS tuberculosis, therapy is often extended to 24 months. It is also recommended that patients with active tuberculosis have directly observed therapy to insure compliance, reduce the development of a resistant organism, and monitor clinical response.
Source...