The effect of streptomycin, one gram daily, with and without para-aminosalicylic acid, ten grams daily, in the course of treating 118 tuberculous lesions of hones and joints in 1947, 1948, 1949, and 1950 has been assessed.
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The courses have varied from a total of as little as thirty grams to cover a surgical operation, to as much as 360 grams in the early days of streptomycin theapy, when three grams a day was used. The most common doses were sixty grams and ninety grams. The cases have been grouped according to the indications for streptomycin rather than to the dosage used.
The best results were obtained when streptomycin treatment was associated with excision of a tuberculous focus. In some instances pyogenic infection had previously been present and controlled by the use of suitable antibacterial agents. Of thirty-five operations through a tuberculous field, primary healing was obtained in thirty-two and delayed healing in three. There were no complete failures.
When persistent tuberculous sinuses from bone were treated by streptomycin, but not by excision, the results were nearly as good, but slower in appearing. Of fourteen uncontaminated sinuses, only Six closed permanetly during treatment; but five more closed after one recurrence, with or without more streptomycin; two closed after excision; and one closed spontaneously ten months after termination of streptomycin therapy. When the added factor of pyogenic bacteria had been faced in eighteen cases, additional antibioties were required, but the results were about the same. There were eleven permanent closures during treatment, four subsequent closures following one recurrence, and three partial failures. Some of these sinuses, so difficult to close, had been draining for between fourteen and twenty-three years, but twenty-nine out of thirty-two (90 per cent.) are now healed. Only one of these appears to be too great a problem to permit a good prognosis to be made.
In the treatment of non-discharging bone lesions, the results attributable to streptomycin in thirty-four cases appeared to be good in twenty cases (59 per cent.) and disappointing in fourteen cases (41 per cent.), when judged by clinical and roentgenographic findings. This group is difficult to assess because of the slowness with which ohjective evidence of healing can be obtained and because the long-term results from standard treatment alone were very good, even before the advent of streptomycin.
When bone and joint lesions were complicated by miliary tuberculosis of the lungs (five cases), treatment was modified by increasing the course of streptomycin to 180 grams spread over six months or more, as well as by the use of intrathecal injections. The results were excellent, as the pulmonary lesions completely disappeared and it was possible ultimately to bone-graft two spine lesions. Two hip lesions appear to have been arrested, one with no hone destruction. One synovial lesion of the knee has been aborted. The surprising results obtained in the three cases last mentioned may indicate that early treatment of bone lesions with adequate doses of streptomycin and para-aminosalicylic acid for a prolonged period of time offers real hope of cure of tuberculosis of bones and joints. In these cases the miliary tuberculosis of the lung necessitated prolonged administration of streptomycin and para-aminosalicylic acid. The patient with a tuberculous knee received 129 grams of streptomycin and 2,290 grams of para-aminosalicylic acid over seven and one-half months; one patient with a hip lesion, 180 grams of streptomycin and 360 grams of para-aminosalicylic acid over six months. There was no destruction of the joint in this case. The second patient with a tuberculous hip received 180 grams of streptomycin and 640 glams of para-aminosalicylic acid over six months, followed by a further course of 2,025 grams of para-aminosalicylic acid over the following four and one-half months. The roentgenograms of this patient are reproduced in Figures 1-A and 1-B.
When tuberculosis of bone was complicated by meningitis, the results were temporarily encouraging but ultimately poor. Only one patient out of five has survived, but he has lived for two and one-half years since the onset of miliary tuberculosis and meningitis.
Sensitivity tests were carried out on all lesions with tubercle bacilli, using modified Herrold's medium. No bacilli were available in 33.0 per cent., the lesions became nonbacillary during treatment in 34.7, and final determinations of sensitivity have been made in only 30.5 per cent. Of this last group, 72 per cent. yielded bacilli sensitive to streptomycin throughout treatment, fourteen per cent. gave bacilli which became resistant, and fourteen per cent. started with resistant bacilli and continued to yield them throughout treatment. Resistant forms of bacilli did not emerge in any patient treated concurrently with both streptomycin and para-aminosalicylic acid, provided the tubercle bacilli were sensitive to begin with, that para-aminosalicylic acid was used from the commencement of streptomycin treatment, and that the dose of para-aminosalicylic acid was not less than ten grams daily.
Response to streptomycin was perhaps impaired to some degree in the patients who harbored resistant forms of tubercle bacilli. However, the only group of patients who have done badly is the group with meningitis, and among the remaining 113 patients there have been only two deaths, one from cerebral embolism and one from a ruptured aneurysm. The prognosis in the least promising of the other 111 is reasonably good.
There is no doubt that the use of streptomycin and para-aminosalicylic acid has reduced morbidity and increased the prospects of successful treatment in the field of bone and joint tuberculosis. It is of the greatest value in promoting primary healing of a closed wound after excision of a tuberculous sinus and its focus of origin.
Toronto Hospital for Tuberculosis, Weston, Ontario