The Treatment of Tuberculous Meningitis in Infants with Streptomycin and Isonicotinic Acid Hydrazide (Isoniazid)

A Preliminary Report of Six Patients Under the Age of Two Years Treated Without Intrathecal Medication.

¹ The Homer Folks Tuberculosis Hospital, Oneonta, New York.

1) Six infants, ranging in age from seven to 21 months, have been treated for tuberculous meningitis on a regimen of streptomycin and isoniazid 10 mg. per kilogram by mouth or by intramuscular injection. All were acutely ill on admission; four were comatose or semi-comatose and two had accompanying miliary tuberculosis.

2) These patients have been treated for periods ranging from four to 13 months. All have shown marked to moderate clinical improvement. The four treated for the longest periods of time have achieved a normal cerebrospinal fluid and have lost all evidence of meningeal irritation and of focal neurological lesions which were present on admission. None has shown any progression of disease and all have shown repeatedly negative spinal fluid cultures for tubercle bacilli and none has had a bacteriological relapse. None has developed cerebrospinal fluid block.

3) There was no evidence of any serious toxic manifestation as a result of the combined use of these drugs for prolonged periods of time. Transient slight albuminuria was frequently seen. Transient maculopapular rashes were seen in two cases and a disturbance of cephalin flocculation in two cases and thymol turbidity in one case. Despite continued therapy, these abnormalities have not persisted or progressed.

4) Significant levels of isoniazid were detected in the spinal fluid one and one-half hours, five hours and even 12 hours after either an oral or intramuscular dose of drug.

5) All these children had associated tuberculosis of the lungs. The patients with associated miliary tuberculosis of the lungs have shown marked improvement in the pulmonary and meningeal manifestations of their disease. Two other patients with parenchymal infiltration have shown marked to moderate improvement by serial roentgenographic examination.

6) It is felt, considering the mortality potential in this age group and with these clinical findings, that a definite favorable change in the course of tuberculous meningitis has been obtained. It is the clinical impression that these results are at least similar to what one would have expected with the regimen employing streptomycin systemically as well as intrathecally in association with or without a sulfone. The disadvantages of intrathecal therapy appear to have been avoided without a loss of bacteriostatic effect. Prolonged therapy on this regimen for a minimum of one year is suggested.

7) Further study of the use of streptomycin in combination with isoniazid in treatment of tuberculous meningitis would appear to be indicated.