Interventions for Tuberculosis Control and Elimination 2002

of six months’ duration with isoniazid plus rifampicin throughout was as
effective as any other regimen. 562 It was concluded that outpatient
chemotherapy with standard short-course chemotherapy based on isoniazid,
rifampicin, and pyrazinamide should be the main management of uncomplicated
spinal tuberculosis. 561
It is likely, based on the results of these studies, that a regimen that
is effective for pulmonary tuberculosis should be equally effective for the
treatment of tuberculosis of the spine.
Tuberculosis of the central nervous system
Tuberculous meningitis is the most important central nervous system manifestation
of tuberculosis. The optimum treatment of tuberculous meningitis
is not known, and recommendations are based on the pharmacokinetic
properties of the medications and, to a large extent, on inference and common
sense.
The blood-brain barrier poses particular problems for the choice of the
right drug combinations as penetration into the cerebrospinal fluid and its
ratio to serum concentrations varies widely among the various anti-tuberculosis
drugs.
The key issue is the extent of plasma binding of the drug, as probably
only the unbound portion penetrates into the central nervous system,
thus explaining the differences between isoniazid and pyrazinamide on one
hand, and rifampicin on the other.
Isoniazid is recognized as a drug with excellent penetration into cerebrospinal
fluid. 61,563
Rifampicin, in contrast to isoniazid, has very poor penetration into cerebrospinal
fluid, 563 but seems to appear in higher concentrations at the beginning
of treatment, in the phase where the meninges are inflamed. 564,565
However, because tuberculosis is not a localized disease, the use of
rifampicin is beneficial for the treatment of lesions other than those in the
central nervous system that may be simultaneously present.
Pyrazinamide has excellent penetration into cerebrospinal fluid. 563
Ethambutol penetrates poorly into normal or uninflamed meninges, but
penetrates fairly well into inflamed meninges. 565-568
Streptomycin penetrates relatively poorly into cerebrospinal fluid. 563
Among the thioamides, ethionamide has been found to have high penetration
into cerebrospinal fluid. 565,568-570
73