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The Streptomycin Treatment of Genito-Urinary Tuberculosis: A Preliminary Report1, 2
THE JOURNAL OF UROLOGY
Vol, 60, No. 6, December 1948
Printed in U.S.A.
THE STREPTOMYCIN TREATMENT OF GENITO-URINARY TUBERCULOSIS: A PRELIMINARY REPORT1 , 2 JOHN K. LATTIMER, WILLIAM H. STEARNS, J. BURNS AMBERSON, JOSEPH SCHWARTZ, ROWLAND GOODMAN AND WILLIAM EAST
From the Veterans Administration Hospital, Bronx, N. Y.
An accurate evaluation of the effectiveness and limitations of streptomycin in the treatment of genito-urinary tuberculosis has been undertaken by this group. The Departments of Medicine and Urology have cooperated closely, recognizing that tuberculosis is not primary in the genito-urinary tract and that pathogenetically it is a disseminated disease. It was interesting to note that from the first 25 patients a total of 11 kidneys and 8 epididymides had been removed before arrival here, without checking the disease. This attests to the frequent ineffectiveness of surgery. Since the optimum dose of streptomycin is not known, a pilot group of 25 patients was treated with 1.8 mg. daily (0.3 gm. every 4 hours intramuscularly) for a period of 120 days. These cases were studied exhaustively. The preliminary results have been encouraging. At least another year must elapse before a really valid report can be rendered however. Some bacteriological data are presented here, based on the 16 cases which have been followed for 1 year. METHODS
Patients with all types and all degrees of tuberculosis were treated. Twentyone of the 25 patients had additional tuberculous lesions outside the genitourinary tract. Positive cultures or guinea pigs from the urine were the criteria required for a diagnosis of genito-urinary tuberculosis. Nine consecutive 24 hour urine specimens were cultured and inoculated into guinea pigs every month during the treatment, and every 3 months thereafter (fig. 1). Cystoscopic examinations were made and the findings drawn graphically on a chart each time, for comparison (fig. 2). Ureteral specimens were taken at each cystoscopy and inoculated into guinea pigs; cultures also were made. Cultures of the bladder urine were made for secondary organisms and a count of the pus cells in each ureteral specimen was made at each cystoscopic examination. The bladder capacity was measured at each cystoscopy. A routine urinalysis was done every 2 weeks along with a blood urea nitrogen, erythrocyte sedimentation rate, phenolsulphonphthalein test, blood count, total serum protein, albumin and globulin determination, and cephalin flocculation test. Retrograde pyelograms were done before and after treatment and every 6 months subsequently. 1 Presented at annual meeting, American Urological Association, Boston, Mass., May 18, 1948. · 2 This study is one part of a coordinated large scale program of investigation into the effects of streptomycin on tuberculosis of all types, now being conducted by the Veterans Administration, the Army and Navy. Since their veteran patients will be followed indefinitely by the Veterans Hospitals they present an unparalleled opportunity for long term follow-up. 974
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
STREPTCM'rtlN- 120 DAYS
I
2
3
9
4
10
II
12
975
13
MONTHS PoS!live cultures may re-appear after long penods wilfl negative findings.
FIG. 1. Voided 24 hour urine cultures were taken in groups of 9, every 3 months
AFTER 120 DAYS STREPTOMYCIN
VOIDED URINE TBC POSITIVE
URINE TBC NEGATIVE
FIG. 2. Cystoscopic findings were recorded graphically before and after treatment and every 3 months subsequently.
Urine cultures were grown first on Petrik's medium and then sub-cultured on Dubos' liquid medium for pure culture streptomycin sensitivity studies. The sensitivities of all cultures ,vere determined. Audiograms and caloric tests
976
LATTIMER ET AL.
were done every 2 weeks on each patient. A careful chart was kept of the frequency of urination, pain on urination and all symptoms and toxic manifestations. DEFINITION OF TERMS
It is important to divide cases of kidney tuberculosis into two clinical categories: first those with small ulcerative lesions, and second, those with large caseous or fibro-caseous lesions. The prognosis may be quite different. The few cases reported in the literature so far were primarily of the advanced type which did not provide the best chance to assess the action of the drug. A correlation of pathological material with the other data will not be attempted here.
Fm. 3. A, left, Example of kidney with a small ulcerative lesion which discharged pus and tubercle bacilli, but was too small to show in pyelogram. B, right, example of kidney distorted by strictures of tuberculosis. PATIENTS WITH SMALL ULCERATIVE RENAL LESIONS
These were the lesions seen so early that they could not be detected by x-ray (fig. 3, A) but which liberated tubercle bacilli into the urine collected from the ureter. These cases presumably had very little caseation or fibrosis present. Such cases rarely find their way to the urologist while they are still in this early stage. They can be detected most commonly among patients who have had one kidney removed because of tuberculosis, and in whom a careful check on the remaining good kidney reveals the appearance of pus cells and tubercle bacilli. Any tuberculous patient who begins to show albuminuria or pyuria should be suspected of having early ulcerative renal lesions. In 5 out of 6 cases of this minimal type the tubercle bacilli disappeared from the urine after streptomycin and the urines have remained negative for a period of 1 year. At the end of 1 year the sixth case sloughed out a cavitating lesion which had apparently been present as a caseous mass in the kidney. The urine then became positive once more for tubercle bacilli.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
977
LARGE RENAL LESIONS
Any kidney which is so badly excavated or distorted by the strictures of tuberculosis that the lesion is visible by x-ray, may not do as well on streptomycin (fig. 3, B). A tuberculous ulceration which is visible in a pyelogram is almost always accompanied by an area of thick fibrous tissue and caseation which probably can not be penetrated adequately by streptomycin. Of the 10 cases which were of this advanced type, with pathological changes visible by x-ray, only 5 cases became negative for tubercle bacilli in the urine and have remained negative for periods over one year. The remaining 5 remainedpositive. Pyelographic cavities did not change significantly even after 1 year of negative urines. This is not surprising in view of the firm consistency of the kidney, which would prevent cavities from collapsing even if improved.
FIG. 4. Ureteral narrowing which disappeared during treatment URETERS
One patient showed a definite ragged narrowing of the lower ureter which disappeared slowly during the 4 months of streptomycin treatment and was normal in appearance at the end of the treatment (fig. 4). We do not know ·whether this narrowing of the ureter was due to edema, to tuberculous granulations or to debris. BLADDER
Superficial cystitis and ulcerations, proven by biopsy to resemble those of tuberculosis, were seen to heal within 8 weeks on streptomycin therapy. 1Vith this healing, symptoms improved strikingly, and bladder capacities increased. When the urine from the kidneys became negative and stayed negative for tubercle bacilli, the ulcerations stayed healed, but where the kidneys broke down and again became positive the lesions in the bladder again appeared. Deep seated bladder disease, such as long-standing contractures, did not improve on streptomycin treatment. In 2 out of the 25 patients there was a marked contracture of the bladder which continued to progress in spite of the streptomycin treatment, leaving these patients ·with markedly contracted bladders and reflux up the ureters to the kidneys. Whether fibrosis and contracture were actually hastened by the treatment could not be determined.
978
LATTIMER ET AL.
PROSTATE GLAND
Twelve of the 25 patients showed nodules in the prostate gland palpable by rectal examination. These nodules were observed to recede or grow larger, independently of the streptomycin treatment. New nodules sometimes appeared during treatment (fig. 5). It was believed that there was no marked improvement which could be attributed to the streptomycin. The caseous nature of prostatic tuberculosis probably explains its failure to respond to streptomycin. Since the prostate glands were not massaged because of the danger of hematogenous dissemination there was no other criterion for the existence of tuberculous prostatitis.
Fm. 5. Prostatic nodules which receded moderately (left) during streptomycin treatment while new nodule (right) appeared despite the drug.
It was noted, however, that the majority of these patients showed a peculiar deformity of the prostatic urethra. In cases with long-standing prostatic involvement there was a dilatation of the prostatic urethra and a dilatation of the prostatic ducts, until they assumed a golf-hole appearance. The epithelium of the prostatic urethra was drawn up into thin folds which intertwined among the dilated prostatic ducts. It is recognized that this sign is not caused exclusively by tuberculosis, but may appear after any prostatitis of sufficient chronicity. Since it appeared in the majority of the patients with prostatic tuberculosis, however, all cases in which these changes were observed were suspected of having tuberculosis and a search for the organisms was made. EPIDIDYMITIS
Chronic nodules in the epididymides, which were thought to be tuberculous, did not change in size or appearance during streptomycin treatment. Acute tuberculous epididymitis, where seen, was not markedly influenced by the streptomycin treatment. The swollen epididymis reduced gradually in size but at about the same rate of improvement that would be expected even in the absence of the streptomycin treatment (fig. 6). It was noted that the few cases observed did not ulcerate through to the skin, however. Abscessed draining epididymides which had not been treated surgically did not improve strikingly with streptomycin treatment. Draining postoperative sinuses of the scrotum, however, which had resulted from the removal of a tuberculous epididymis or testis were quick to respond to treatment with streptomycin. Six such patients healed up within 3 weeks and have remained healed since. It must be emphasized that the tuberculous epididymis had already been removed before the treatment was given.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
979
A total of 112 cases has now been treated by the Government group and the results have been similar. The follow-up period has not yet been long enough to permit conclusions to be drawn, from this group, however. TOXICITY
On this regimen all of the 25 patients developed a loss of vestibular function, as measured by caloric tests. Some patients were markedly dizzy and some patients were not dizzy at all, but all of the patients showed a loss of vestibular response, after about 30 days of treatment. After treatment was stopped the patients' dizziness began to improve and with the addition of eye exercises and coordination exercises, the ataxia has been compensated for by almost everyone. Hearing loss was not a prominent feature on this regimen. Only one of the 25 patients showed any decrease in hearing acuity and this patient had been deficient even before treatment was started. When treatment was stopped his acuity returned to its previous level. Rises in nonprotein nitrogen were not
Frn. 6. Acute tuberculous epididymitis did not recede any more promptly than usual with streptomycin.
marked although in some cases there was a slight transitory rise to about 40. Since many of these patients had only one fragment of a solitary kidney remaining, and since their kidney function did not suffer, it was concluded that this dosage was not markedly toxic for the kidneys. Mild transitory skin rashes appeared in several of the patients on about the tenth day of treatment. These abated with anti-histamine drugs, but in 2 of the 25 patients the skin rash reappeared at about the sixtieth day of treatment and became a severe exfoliative dermatitis which necessitated the curtailment of treatment. When treatment was stopped the skin rashes disappeared. No patients have died. PRESENT TREATMENT REGIMENS
Since the longer, more intensive treatment (120 days with 1.8 gm. daily) in divided doses proved moderately toxic, and since resistance to streptomycin developed in many of the cases at about 6 weeks, it was decided that a series of cases would be treated with a course of 1 gm. of streptomycin daily for a period of 6 weeks (0.5 gm. every 12 hours intramuscularly). It was further decided that any operative procedure, either a nephrectomy or epididymectomy, which
980
LATTIMER ET AL.
was to be done upon a tuberculous organ would be accompanied by a 3 week course of streptomycin (0.5 gm. every 12 hours). The empirical nature of these dosages must be recognized. They may or may not prove as effective as the larger dosage. RESISTANCE
The tubercle bacilli from all patients were sensitive to streptomycin at the beginning of treatment. In those cases which continued to show tubercle bacilli, there was a marked rise in resistance as time went on (fig. 7). CONCLUSIONS
Dosage. The dosage (1.8 gm. daily for 120 days) was experimental and proved moderately toxic. A dosage of 1 gm. for a shorter period (0.5 gm. every 12
D~VELOPMENT OF RESISTANCE
OF TUBERCLE BACILLI
FROM CASE Na 2
ir'ooo
I i
.RESISTANT
iS
e:;soo
.SENSITIVE
a::
t;:;
r2 ('5 250
z r':!
\/2
~
50
- I
-
I
80DAYS
FIG. 7. Tubercle bacilli which persisted in urine after treatment became highly resistant to streptomycin.
hours, for 6 weeks) is now being tried. The development of resistance to streptomycin limited its usefulness in some cases. Kidney tiiberculosis. The urines from most cases with minimal lesions have stayed free from tubercle bacilli to date. Some cases with advanced lesions have also stayed free to date. Except for general toxic effects the treatment was well tolerated by patients with unilateral, with bilateral and with solitary tuberculous kidneys. Unilateral renal lesions which were typical by pyelogram failed to respond to streptomycin in 50 per cent of the cases. At present we believe that such patients should have a nephrectomy, followed by only 3 weeks of streptomycin (0.5 gm. every 12 hours) and by 6 months or more of sanatorium care. Bladder tuberculosis. Superficial cystitis and ulcerations improved markedly, causing symptoms to improve and bladder capacities to increase. Deep seated bladder contractures were not improved.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
981
Genital tuberculosis. Prostatic nodules were not appreciably affected. In those cases in -which epididymitis was present, streptomycin did not cause the swelling and tenderness to abate more rapidly. Hmvever, no ulceration through the skin occurred. All postoperative draining scrotal sinuses became dry after 3 weeks of streptomycin. Since tuberculosis of the epididymis was apparently benefited so little by streptomycin, surgery, when indicated, is now employed for the purely genital cases. Streptomycin is given prophylactically for 3 weeks at the time of operation, starting 2 days before operation, and continuing for 19 days after operation. Years of follow-up will be necessary to evaluate these results correctly, It must be remembered that genito-urinary tuberculosis usually implies the presence of tuberculous foci in both of the kidneys and in other organs. These too, must be adequately treated. Our bacteriologist Irving Zahler, head nurse Miss Lydia R. Sechler and her staff, our secretary Miss Alfreda Jastremski, illustrators Shapiro, Barlow and staff and the staff of the Kingsbridge Veterans Hospital, have been most helpful in this work Vife wish to express our appreciation to consultant Dr, Archie L. Dean for sponsoring this presentation.
Vol, 60, No. 6, December 1948
Printed in U.S.A.
THE STREPTOMYCIN TREATMENT OF GENITO-URINARY TUBERCULOSIS: A PRELIMINARY REPORT1 , 2 JOHN K. LATTIMER, WILLIAM H. STEARNS, J. BURNS AMBERSON, JOSEPH SCHWARTZ, ROWLAND GOODMAN AND WILLIAM EAST
From the Veterans Administration Hospital, Bronx, N. Y.
An accurate evaluation of the effectiveness and limitations of streptomycin in the treatment of genito-urinary tuberculosis has been undertaken by this group. The Departments of Medicine and Urology have cooperated closely, recognizing that tuberculosis is not primary in the genito-urinary tract and that pathogenetically it is a disseminated disease. It was interesting to note that from the first 25 patients a total of 11 kidneys and 8 epididymides had been removed before arrival here, without checking the disease. This attests to the frequent ineffectiveness of surgery. Since the optimum dose of streptomycin is not known, a pilot group of 25 patients was treated with 1.8 mg. daily (0.3 gm. every 4 hours intramuscularly) for a period of 120 days. These cases were studied exhaustively. The preliminary results have been encouraging. At least another year must elapse before a really valid report can be rendered however. Some bacteriological data are presented here, based on the 16 cases which have been followed for 1 year. METHODS
Patients with all types and all degrees of tuberculosis were treated. Twentyone of the 25 patients had additional tuberculous lesions outside the genitourinary tract. Positive cultures or guinea pigs from the urine were the criteria required for a diagnosis of genito-urinary tuberculosis. Nine consecutive 24 hour urine specimens were cultured and inoculated into guinea pigs every month during the treatment, and every 3 months thereafter (fig. 1). Cystoscopic examinations were made and the findings drawn graphically on a chart each time, for comparison (fig. 2). Ureteral specimens were taken at each cystoscopy and inoculated into guinea pigs; cultures also were made. Cultures of the bladder urine were made for secondary organisms and a count of the pus cells in each ureteral specimen was made at each cystoscopic examination. The bladder capacity was measured at each cystoscopy. A routine urinalysis was done every 2 weeks along with a blood urea nitrogen, erythrocyte sedimentation rate, phenolsulphonphthalein test, blood count, total serum protein, albumin and globulin determination, and cephalin flocculation test. Retrograde pyelograms were done before and after treatment and every 6 months subsequently. 1 Presented at annual meeting, American Urological Association, Boston, Mass., May 18, 1948. · 2 This study is one part of a coordinated large scale program of investigation into the effects of streptomycin on tuberculosis of all types, now being conducted by the Veterans Administration, the Army and Navy. Since their veteran patients will be followed indefinitely by the Veterans Hospitals they present an unparalleled opportunity for long term follow-up. 974
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
STREPTCM'rtlN- 120 DAYS
I
2
3
9
4
10
II
12
975
13
MONTHS PoS!live cultures may re-appear after long penods wilfl negative findings.
FIG. 1. Voided 24 hour urine cultures were taken in groups of 9, every 3 months
AFTER 120 DAYS STREPTOMYCIN
VOIDED URINE TBC POSITIVE
URINE TBC NEGATIVE
FIG. 2. Cystoscopic findings were recorded graphically before and after treatment and every 3 months subsequently.
Urine cultures were grown first on Petrik's medium and then sub-cultured on Dubos' liquid medium for pure culture streptomycin sensitivity studies. The sensitivities of all cultures ,vere determined. Audiograms and caloric tests
976
LATTIMER ET AL.
were done every 2 weeks on each patient. A careful chart was kept of the frequency of urination, pain on urination and all symptoms and toxic manifestations. DEFINITION OF TERMS
It is important to divide cases of kidney tuberculosis into two clinical categories: first those with small ulcerative lesions, and second, those with large caseous or fibro-caseous lesions. The prognosis may be quite different. The few cases reported in the literature so far were primarily of the advanced type which did not provide the best chance to assess the action of the drug. A correlation of pathological material with the other data will not be attempted here.
Fm. 3. A, left, Example of kidney with a small ulcerative lesion which discharged pus and tubercle bacilli, but was too small to show in pyelogram. B, right, example of kidney distorted by strictures of tuberculosis. PATIENTS WITH SMALL ULCERATIVE RENAL LESIONS
These were the lesions seen so early that they could not be detected by x-ray (fig. 3, A) but which liberated tubercle bacilli into the urine collected from the ureter. These cases presumably had very little caseation or fibrosis present. Such cases rarely find their way to the urologist while they are still in this early stage. They can be detected most commonly among patients who have had one kidney removed because of tuberculosis, and in whom a careful check on the remaining good kidney reveals the appearance of pus cells and tubercle bacilli. Any tuberculous patient who begins to show albuminuria or pyuria should be suspected of having early ulcerative renal lesions. In 5 out of 6 cases of this minimal type the tubercle bacilli disappeared from the urine after streptomycin and the urines have remained negative for a period of 1 year. At the end of 1 year the sixth case sloughed out a cavitating lesion which had apparently been present as a caseous mass in the kidney. The urine then became positive once more for tubercle bacilli.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
977
LARGE RENAL LESIONS
Any kidney which is so badly excavated or distorted by the strictures of tuberculosis that the lesion is visible by x-ray, may not do as well on streptomycin (fig. 3, B). A tuberculous ulceration which is visible in a pyelogram is almost always accompanied by an area of thick fibrous tissue and caseation which probably can not be penetrated adequately by streptomycin. Of the 10 cases which were of this advanced type, with pathological changes visible by x-ray, only 5 cases became negative for tubercle bacilli in the urine and have remained negative for periods over one year. The remaining 5 remainedpositive. Pyelographic cavities did not change significantly even after 1 year of negative urines. This is not surprising in view of the firm consistency of the kidney, which would prevent cavities from collapsing even if improved.
FIG. 4. Ureteral narrowing which disappeared during treatment URETERS
One patient showed a definite ragged narrowing of the lower ureter which disappeared slowly during the 4 months of streptomycin treatment and was normal in appearance at the end of the treatment (fig. 4). We do not know ·whether this narrowing of the ureter was due to edema, to tuberculous granulations or to debris. BLADDER
Superficial cystitis and ulcerations, proven by biopsy to resemble those of tuberculosis, were seen to heal within 8 weeks on streptomycin therapy. 1Vith this healing, symptoms improved strikingly, and bladder capacities increased. When the urine from the kidneys became negative and stayed negative for tubercle bacilli, the ulcerations stayed healed, but where the kidneys broke down and again became positive the lesions in the bladder again appeared. Deep seated bladder disease, such as long-standing contractures, did not improve on streptomycin treatment. In 2 out of the 25 patients there was a marked contracture of the bladder which continued to progress in spite of the streptomycin treatment, leaving these patients ·with markedly contracted bladders and reflux up the ureters to the kidneys. Whether fibrosis and contracture were actually hastened by the treatment could not be determined.
978
LATTIMER ET AL.
PROSTATE GLAND
Twelve of the 25 patients showed nodules in the prostate gland palpable by rectal examination. These nodules were observed to recede or grow larger, independently of the streptomycin treatment. New nodules sometimes appeared during treatment (fig. 5). It was believed that there was no marked improvement which could be attributed to the streptomycin. The caseous nature of prostatic tuberculosis probably explains its failure to respond to streptomycin. Since the prostate glands were not massaged because of the danger of hematogenous dissemination there was no other criterion for the existence of tuberculous prostatitis.
Fm. 5. Prostatic nodules which receded moderately (left) during streptomycin treatment while new nodule (right) appeared despite the drug.
It was noted, however, that the majority of these patients showed a peculiar deformity of the prostatic urethra. In cases with long-standing prostatic involvement there was a dilatation of the prostatic urethra and a dilatation of the prostatic ducts, until they assumed a golf-hole appearance. The epithelium of the prostatic urethra was drawn up into thin folds which intertwined among the dilated prostatic ducts. It is recognized that this sign is not caused exclusively by tuberculosis, but may appear after any prostatitis of sufficient chronicity. Since it appeared in the majority of the patients with prostatic tuberculosis, however, all cases in which these changes were observed were suspected of having tuberculosis and a search for the organisms was made. EPIDIDYMITIS
Chronic nodules in the epididymides, which were thought to be tuberculous, did not change in size or appearance during streptomycin treatment. Acute tuberculous epididymitis, where seen, was not markedly influenced by the streptomycin treatment. The swollen epididymis reduced gradually in size but at about the same rate of improvement that would be expected even in the absence of the streptomycin treatment (fig. 6). It was noted that the few cases observed did not ulcerate through to the skin, however. Abscessed draining epididymides which had not been treated surgically did not improve strikingly with streptomycin treatment. Draining postoperative sinuses of the scrotum, however, which had resulted from the removal of a tuberculous epididymis or testis were quick to respond to treatment with streptomycin. Six such patients healed up within 3 weeks and have remained healed since. It must be emphasized that the tuberculous epididymis had already been removed before the treatment was given.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
979
A total of 112 cases has now been treated by the Government group and the results have been similar. The follow-up period has not yet been long enough to permit conclusions to be drawn, from this group, however. TOXICITY
On this regimen all of the 25 patients developed a loss of vestibular function, as measured by caloric tests. Some patients were markedly dizzy and some patients were not dizzy at all, but all of the patients showed a loss of vestibular response, after about 30 days of treatment. After treatment was stopped the patients' dizziness began to improve and with the addition of eye exercises and coordination exercises, the ataxia has been compensated for by almost everyone. Hearing loss was not a prominent feature on this regimen. Only one of the 25 patients showed any decrease in hearing acuity and this patient had been deficient even before treatment was started. When treatment was stopped his acuity returned to its previous level. Rises in nonprotein nitrogen were not
Frn. 6. Acute tuberculous epididymitis did not recede any more promptly than usual with streptomycin.
marked although in some cases there was a slight transitory rise to about 40. Since many of these patients had only one fragment of a solitary kidney remaining, and since their kidney function did not suffer, it was concluded that this dosage was not markedly toxic for the kidneys. Mild transitory skin rashes appeared in several of the patients on about the tenth day of treatment. These abated with anti-histamine drugs, but in 2 of the 25 patients the skin rash reappeared at about the sixtieth day of treatment and became a severe exfoliative dermatitis which necessitated the curtailment of treatment. When treatment was stopped the skin rashes disappeared. No patients have died. PRESENT TREATMENT REGIMENS
Since the longer, more intensive treatment (120 days with 1.8 gm. daily) in divided doses proved moderately toxic, and since resistance to streptomycin developed in many of the cases at about 6 weeks, it was decided that a series of cases would be treated with a course of 1 gm. of streptomycin daily for a period of 6 weeks (0.5 gm. every 12 hours intramuscularly). It was further decided that any operative procedure, either a nephrectomy or epididymectomy, which
980
LATTIMER ET AL.
was to be done upon a tuberculous organ would be accompanied by a 3 week course of streptomycin (0.5 gm. every 12 hours). The empirical nature of these dosages must be recognized. They may or may not prove as effective as the larger dosage. RESISTANCE
The tubercle bacilli from all patients were sensitive to streptomycin at the beginning of treatment. In those cases which continued to show tubercle bacilli, there was a marked rise in resistance as time went on (fig. 7). CONCLUSIONS
Dosage. The dosage (1.8 gm. daily for 120 days) was experimental and proved moderately toxic. A dosage of 1 gm. for a shorter period (0.5 gm. every 12
D~VELOPMENT OF RESISTANCE
OF TUBERCLE BACILLI
FROM CASE Na 2
ir'ooo
I i
.RESISTANT
iS
e:;soo
.SENSITIVE
a::
t;:;
r2 ('5 250
z r':!
\/2
~
50
- I
-
I
80DAYS
FIG. 7. Tubercle bacilli which persisted in urine after treatment became highly resistant to streptomycin.
hours, for 6 weeks) is now being tried. The development of resistance to streptomycin limited its usefulness in some cases. Kidney tiiberculosis. The urines from most cases with minimal lesions have stayed free from tubercle bacilli to date. Some cases with advanced lesions have also stayed free to date. Except for general toxic effects the treatment was well tolerated by patients with unilateral, with bilateral and with solitary tuberculous kidneys. Unilateral renal lesions which were typical by pyelogram failed to respond to streptomycin in 50 per cent of the cases. At present we believe that such patients should have a nephrectomy, followed by only 3 weeks of streptomycin (0.5 gm. every 12 hours) and by 6 months or more of sanatorium care. Bladder tuberculosis. Superficial cystitis and ulcerations improved markedly, causing symptoms to improve and bladder capacities to increase. Deep seated bladder contractures were not improved.
STREPTOMYCIN AND GENITO-URINARY TUBERCULOSIS
981
Genital tuberculosis. Prostatic nodules were not appreciably affected. In those cases in -which epididymitis was present, streptomycin did not cause the swelling and tenderness to abate more rapidly. Hmvever, no ulceration through the skin occurred. All postoperative draining scrotal sinuses became dry after 3 weeks of streptomycin. Since tuberculosis of the epididymis was apparently benefited so little by streptomycin, surgery, when indicated, is now employed for the purely genital cases. Streptomycin is given prophylactically for 3 weeks at the time of operation, starting 2 days before operation, and continuing for 19 days after operation. Years of follow-up will be necessary to evaluate these results correctly, It must be remembered that genito-urinary tuberculosis usually implies the presence of tuberculous foci in both of the kidneys and in other organs. These too, must be adequately treated. Our bacteriologist Irving Zahler, head nurse Miss Lydia R. Sechler and her staff, our secretary Miss Alfreda Jastremski, illustrators Shapiro, Barlow and staff and the staff of the Kingsbridge Veterans Hospital, have been most helpful in this work Vife wish to express our appreciation to consultant Dr, Archie L. Dean for sponsoring this presentation.