Bacterial Fibrinolysin, its Possible Therapeutic Application in Tuberculous Meningitis.

A constant feature at autopsy in cases dying from tuberculous meningitis, whether treated with streptomycin or not, is a gelatinous exudate at the base of the brain. Frequently this is found in association with, or causing, hydrocephalus, and once the exudate has been formed it is difficult to visualize how streptomycin treatment alone could achieve its resolution. Even were streptomycin able to penetrate and sterilize the exudate the most likely end result would be its organization to fibrous tissue with an increase in the conditions leading to hydrocephalus. The known propensity of cerebrospinal fluid from cases of tuberculous meningitis to form spider's web clots on standing which give the reactions of fibrin, combined with the fibrinous nature of the exudate, has led to the consideration of other forms of therapy in combination with streptomycin which might inhibit fibrin formation in the thecal space. Of the possible anticoagulants, heparin has received the most attention. The drawback that it forms a deposit with streptomycin may be avoided by spaced dosage or by the method of St. Hil and others (1948), in which heparin is added to streptomycin until no further deposition occurs, after which the supematant fluid is removed by decantation. This supernatant fluid contains all the streptomycin used, and heparin may be added to it without the formation of a deposit. Our experience of this combination has been disappointing as judged by the results seen in several patients at autopsy, and, indeed, although it is likely that heparin may prevent the deposition of further fibrin it is improbable that it would have any effect upon the fibrinous exudate, which presumably is already present when the diagnosis of tuberculous meningitis is made. For this reason some other means was sought which would have an action more of a lytic than of a preventive nature, and eventually it was decided to investigate the possibilities of the fibrinolysin produced by some strains of bacteria. The fibrinolysin produced by pathogenic strains of haemolytic streptococci has been examined by Tillett and Garner (1933), Lancefield and Hare (1935), Colebrook and others (1935), and by others, and a few preliminary experiments with Group A haemolytic streptococci showed that when grown in broth they produced varying amounts of a substance which was capable of lysing human fibrin ctots. The variability of yield of lysin from different strains of streptococcus, and even of day-today cultures from the same strain, was overcome when Dr. C. Lack drew my attention to the strain of Strep. pyogenes known as H.64, a strain known for its abundant pr-oduction of fibrinolysin. Since then only this organism has been used, and it has given consistently good yields of lysin.