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Urinary Tract Infection and Renal Homotransplantation: I. Effect of Antibacterial Irrigations on Defenses of the Defunctionalized Bladder
Vol. 101, Apr Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1969 by The Williams & Wilkins Co.
URINARY TRACT INFECTION AND RENAL HOMOTRANSPLANTATION: I. EFFECT OF ANTIBACTERIAL IRRIGATIONS ON DEFENSES OF THE DEFUNCTIONALIZED BLADDER FRANK HINMAN, JR.
AND
FOLKERT 0. BELZER
From the Division of Urology and Department of Surgery, University of California School of Medicine, San Francisco, California
Previous studies in normal human subjects suggested that sterility was regained after vesical contamination by 2 mechanisms:1 1) a washout achieved by exchanging the volume of urine more rapidly than the rate of bacterial doubling2 and 2) intrinsic defenses in or on the vesicourethral mucosa. In an attempt to differentiate the effects of intrinsic from mechanical defenses in the bladder, bacteriologic studies were done on experimental animals before and after urinary diversion by ureterosigmoidostomy,3 and on human patients before and after bilateral nephrectomy prior to renal homotransplantation, 4 with observations on the effect of antibacterial irrigation on vesical bacteria. MATERIALS AND METHODS
The urine was cultured from 57 of 74 patients with end-stage renal disease who were scheduled for homotransplantation. Bilateral nephrectomy was then performed. Eight of these patients had a second transplant so that a total of 65 anephric periods are included in this study. During the anuric period, which lasted from 2 days to more than 1 month, up to 5 bladder irrigations were done on each patient. Each of these consisted of Accepted for publication May 15, 1968. Supported by the Research Evaluation and Allocation Committee, University of California School of Medicine and the United States Public Health Service Grant AM 10045. 1 Cox, C. E. and Hinman, F., Jr.: Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder defense to infection. J. Urol., 86: 739-748, 1961. 2 Hinman, F., Jr. and Cox, C. E.: The voiding vesical defense mechanism: the mathematical effect of residual urine, voiding interval and volume of bacteriuria. J. Urol., 96: 491-498, 1966. 3 Schmaelzle, J. F., Cass, A. S. and Hinman, F., Jr.: Effect of disuse and restoration of function on vesical capacity. J. Urol., May 1969. 4 Hinman, F., Jr., Schmaelzle, J. F. and Belzer, F. 0.: Urinary tract infection and renal homotransplantation. II. Post-transplantation bacterial invasion. J. Urol., May 1969. 477
insertion of a catheter with sterile precautions and irrigation of the bladder with sterile saline solution. A portion of the initial irrigant was sent. for culture and colony count. The finding of any bacteria was considered positive, since resident. flora and infection cannot be separated by determination of numbers of colonies in a washout solution. Instillation of 50 ml. of a 1 per cent solution of neomycin sulfate was made and was retained in the bladder for 15 minutes by clamping the catheter. RESULTS
I nfiuence of pre-nephrectomy infection on the number of organisms recovered during ,bladder irrigation. Bacteria (from <100 to >1,000 organisms per ml.) were present in the urine of 47 per cent of patients immediately prior to bilateral nephrectomy and 43 per cent during subsequent bladder irrigation. Of those patients whose pre-nephrectomy culture was positive, 48 per cent had no bacteria during subsequent irrigation. Of those patients whose urine was initially sterile, 72 per cent remained so (fig. 1). Among the 15 patients with positive cultures both before nephrectomy and during irrigation, half had the same organism recovered from both studies (see table). Ejfect of bladder irrigation on post-transplantation infection. Eleven patients had no bladder irrigations during their anephric period while 54 patients were irrigated at least once with saline and neomycin sulfate solution, averaging 3 irrigations per patient, usually in a 1 to 2-week interval (fig. 2). During the post-transplant period of retention catheterization, half of the non-irrigated patients were bacteriuric compared to only a quarter of the irrigated patients (fig. 3). After removal of the catheter, both became bacteriuric in approximately the same proportion (73 vs. 79 per cent). Of the 30 patients with more significant subsequent infection, that is, with colony counts of
'47S
HINMAN AND BELZER
BACTERIAL RECOVERY DURING ANEPHRIC PERIOD
STERILE BEl=ORE NEPHRECTOMY
POSITIVE BEF'ORE NEPHRECTOMY Fm. 1
Relation of organisms in the pre-nephrectomy cultures to those recovered from bladder irrigations
No preceding infection: No organisms on irrigation Organisms on irrigation
17 8
Total 25 Preceding infection: No organisms on irrigation Organisms on irrigation
14 15 Total 29
Correlation between organisms: Present Absent
7 8
more than 1,000 per ml., 13 had had organisms recovered on irrigation. Of these, 7 had the same organism in both the irrigation fluid and in the post-transplant catheterization specimens. Ejfect of nephrectomy-transplant interval on bacteria from bladder irrigation. Delay in transplantation after nephrectomy did not increase the number of positive cultures during sequential bladder irrigations, which indicates that the duration of the anuria was not a factor (fig. 4). Relation of organisms after second transplantation to those after the first. Eight patients had a second renal transplant after failure and removal
of the first. Six of them had colony counts of more than 1,000 colonies per ml. after the second transplantation, compared to 2 patients after the first. Analysis of the types of organisms involved showed no correlation between the flora after the two procedures. Perhaps more significantly, whereas none of these patients had bacteriuria during the first period of retention catheterization, half of them had more than 1,000 organisms per ml. during the second catheterization period. DISCUSSION
Direct evidence for non-urinary defense mechanisms is limited, but is accumulating. Vivaldi and associates showed that bacteria are not recoverable if placed on the exposed vesical mucosa of the rabbit. 5 Norden and Kass placed radioactive bacteria in the bladders of female guinea pigs. 6 Although the animals promptly voided much of the inoculum, enough remained to determine that the total number of recoverable 5 Vivaldi, E., Munoz, J., Cotran, R. and Kass, E. H.: Factors affecting the clearance of bacteria within the urinary tract. In: Progress in Pyelonephritis. Edited by E. H. Kass. Philadelphia: F. A. Davis, Co., p. 531, 1965. . 6 Norden, C. W. and Kass, E. H.: Bladder antibacterial defense mechanisms. In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967.
URINARY TRACT INFECTION AND RENAL HOiVIO'TRANSPLANTATION.
ANUA.!C INTERVAL !N PA.Tl ENTS WITH AND WITI-IOUT BLADDER IRRIGATION
c::::J /3LADDE,Q !P.P.IGATIO/\l ($4 PATIENT.SJ
IBill'll NO l3LA0DE:.R
(II PAT/E.NTS
40
20
0
0-1
2-8
9-30
>30
DAYS INTERVAL BETWEEN NEPHRECTOMY AND TRANSPLANTATION
Fm. 2
E:l=FECT OF NEOMYCIN BLADDER IRRIGATIONS ON POST TRANSPLANTATION IN!=ECTION
NO 13LADOER IRRIGATION
WITH .RETENTION
CATHETER
CATHETER REMOVED
0
40
20 PER
CENT
60
PATIENTS
FIG. 3
80 iNF"ECTED
100
480
HINMAN AND BELZER
EFFECT OJ:" INTERVAL BETWEEN NEPHRECTOMY AND TRANSPLANTATION ON VESICAL BACTERIA 2-8
DAYS STERILE CULTURE
POSITIVE CULTURE
9-30
DAYS
>
i!SO
DAYS
0
40
20 PER
60
CENT
80
100
PATIENTS
FIG. 4
living bacteria was much lower than the radioactive count of the bladder. Calculating the percentage killed, it was shown that intrinsic defense mechanisms reduced the count by at least one log number in at least 4 hours. In some cases the reduction was by 2 and 2H log numbers. Other mechanisms such as bacterial clumping, effect of urinary constituents and phagocytosis did not play an important role. That bactericidal antibodies or bladder mucosal metabolites were active could only be speculated. Kay, in similar experiments, noted a slight decrease in radioactivity after 8 hours but a great decrease in the numbers of bacterial colonies. 7 By 24 hours both had decreased with half found in the cage or on the perineum of the rat and half in the animal itself. The mechanism of removal appeared to involve phagocytosis since bacteria were found adherent to the vesical mucosa in half an hour in quick-frozen specimens and white blood cells were always found on the mucosal surface by 4 hours. Furthermore, actual phagocytosis was seen. Drach and Cox were able to support this observation by finding immuno7 Kay, D.: Comments. In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967.
:fluorescence in white blood cells in the vesical submucosa in cases of cystitis due to Escherichia coli. 8 They suggested that these bacteria were either caught on the surface or were drawn through the mucosa by the phagocytes. Another defense mechanism, in male patients at least, may be the antibacterial activity of prostatic :fl.uid. 9 , 10 It has been suggested that ejaculatory movements at the end of voiding in the male patient may distribute the fluid in the urethra and bladder.11 Equivalent secretions have not been demonstrated m the female patient. That a resident flora exists m the normal urethra in both sexes has been well demonstrated.12 · 13 Its distribution is altered by many 8 Drach, G. W. and Cox, C. E.: Immunofluorescence studies of the bladder defense mechanism. I. Localization of Escherichia coli in the human bladder. J. Amer. Geriat. Soc., 16: 1114--1124, 1967. 9 Fair, W.R. and Stamey, T. A.: In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967. 10 Gupta, S. N., Perkash, I., Agarwal, S. C. and Anand, S. S.: Antibacterial activity of human prostatic fluid. Invest. Urol., 6: 219, 1967. 11 Hinman, F., Jr.: Bacterial elimination. J. Urol., 99: 811-825, 1968. 12 Helmholz, H. F., Sr.: Determination of the bacterial content of the urethra: a new method,
URINARY TRACT INFECTION AND RENAL HOMOTRANSPLANTATION
poorly understood factors. One fact has emerged, however: pathogenic bacteria may establish themselves in the urethra prior to an attack of cystitis. 14 Perhaps the uremic state of transplant candidates alters the local urethral environment and allows redistribution and change of species. The experiments on dogs indicate that, at least if the urethra is manipulated by a catheter which may simultaneously introduce bacteria, the bladder is not protected against a certain, low resident flora. 3 Since these are the same circumstances surrounding the anephric phase of human transplantation, the findings have some practical relevance. However, the ability of the intrinsic vesical defenses to reject spontaneously introduced bacteria is not tested by these experiments, but experiments are being completed which avoid the urethral approach to culturing of the bladder contents and so may give a more direct answer. In human subjects, bacteriuria is not always perpetuated into the anephric period. (Among those bladders initially infected, 48 per cent were later sterile, although more than a quarter of the initially sterile bladders lost their sterility in the anephric period.) Adverse factors are often present in these patients, such as uremia and anemia, as well as the effects of urethral instrumentation. Instrumentation itself alters the distribution of the flora. 15 Since these transplant patients have all been catheterized and recatheterized, movement of bacterial populations may occur. No data are available to support this assumption, although Guttmann and Frankel's observation that repeated catheterization of 409 male patients who were not emptying their bladders because of neurogenic bladder did not produce infection in 64.8 per cent, suggests that instrumentation itself does not necessarily contaminate the bladder .16 with results of a study of 82 men. J. Urol., 64: 158-166, 1950.
13 Cox, C. E.: The urethra and its relationship to urinary tract infection: the flora of the normal female urethra. Southern Med. J., 59: 621, 1966. 14 Cox, C. E., Lacy, S.S. and Hinman, F., Jr.: The urethra and its relationship to urinary tract infection. II. The urethral flora of the female with recurrent urinary infection. J. Urol., 99: 632-638,
1968.
15 Drouin, G. and Hinman, F., Jr.: Unpublished observations. 16 Guttmann, L. and Frankel, H.: The value of
481
The immediate protective effect of antibacterial irrigation was seen when only a quarter of irrigated patients had bacteria during the immediate post-transplantation period while half the non-irrigated patients had bacteria. Later, after removal of the retention catheter and the opportunity provided for urethral bacteria to invade the bladder, the prior irrigations no longer exerted an effect. That no correlation exists between the duration of anuria and infection of the bladder suggests that defense factors either are or are not operative in any given case. The finding of an appreciably higher incidence of infection after a second homotransplant would indicate that the manipulations and medications attendant on repetition of the procedure weaken the bladder defenses and increase the opportunity for introduction of bacteria. SUMMARY AND CONCLUSIONS
Of 65 patients rendered anuric by bilateral nephrectomy prior to renal homotransplantation, 72 per cent of those initially sterile remained sterile during the period of anuria. If previously infected, 48 per cent were then sterile. Immediately after transplantation, threefourths of patients who had been given bladder irrigations with 1 per cent neomycin sulfate solution were sterile compared to one third of those not irrigated. However, later cultures after removal of the catheter showed no difference between the groups. The same organism persisted in half the patients with positive cultures obtained both during anuria and subsequently. Delay in transplantation did not increase the frequency of positive cultures during the anuric period. A second transplantation resulted in a much higher incidence of bacteriuria. The conclusion is reached that the normal vesicourethral defenses are greatly altered in the clinical anuric state, probably because of effects of uremia and repeated instrumentation of the lower urinary tract. Irrigation with antibacterial solutions transiently reduces the mc1dence of bacterial invasion of the bladder. intermittent catheterisation in the early management of traumatic paraplegia and tetraplegia. Paraplegia, 4: 63, 1966.
THE JOURNAL OF UROLOGY
Copyright © 1969 by The Williams & Wilkins Co.
URINARY TRACT INFECTION AND RENAL HOMOTRANSPLANTATION: I. EFFECT OF ANTIBACTERIAL IRRIGATIONS ON DEFENSES OF THE DEFUNCTIONALIZED BLADDER FRANK HINMAN, JR.
AND
FOLKERT 0. BELZER
From the Division of Urology and Department of Surgery, University of California School of Medicine, San Francisco, California
Previous studies in normal human subjects suggested that sterility was regained after vesical contamination by 2 mechanisms:1 1) a washout achieved by exchanging the volume of urine more rapidly than the rate of bacterial doubling2 and 2) intrinsic defenses in or on the vesicourethral mucosa. In an attempt to differentiate the effects of intrinsic from mechanical defenses in the bladder, bacteriologic studies were done on experimental animals before and after urinary diversion by ureterosigmoidostomy,3 and on human patients before and after bilateral nephrectomy prior to renal homotransplantation, 4 with observations on the effect of antibacterial irrigation on vesical bacteria. MATERIALS AND METHODS
The urine was cultured from 57 of 74 patients with end-stage renal disease who were scheduled for homotransplantation. Bilateral nephrectomy was then performed. Eight of these patients had a second transplant so that a total of 65 anephric periods are included in this study. During the anuric period, which lasted from 2 days to more than 1 month, up to 5 bladder irrigations were done on each patient. Each of these consisted of Accepted for publication May 15, 1968. Supported by the Research Evaluation and Allocation Committee, University of California School of Medicine and the United States Public Health Service Grant AM 10045. 1 Cox, C. E. and Hinman, F., Jr.: Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder defense to infection. J. Urol., 86: 739-748, 1961. 2 Hinman, F., Jr. and Cox, C. E.: The voiding vesical defense mechanism: the mathematical effect of residual urine, voiding interval and volume of bacteriuria. J. Urol., 96: 491-498, 1966. 3 Schmaelzle, J. F., Cass, A. S. and Hinman, F., Jr.: Effect of disuse and restoration of function on vesical capacity. J. Urol., May 1969. 4 Hinman, F., Jr., Schmaelzle, J. F. and Belzer, F. 0.: Urinary tract infection and renal homotransplantation. II. Post-transplantation bacterial invasion. J. Urol., May 1969. 477
insertion of a catheter with sterile precautions and irrigation of the bladder with sterile saline solution. A portion of the initial irrigant was sent. for culture and colony count. The finding of any bacteria was considered positive, since resident. flora and infection cannot be separated by determination of numbers of colonies in a washout solution. Instillation of 50 ml. of a 1 per cent solution of neomycin sulfate was made and was retained in the bladder for 15 minutes by clamping the catheter. RESULTS
I nfiuence of pre-nephrectomy infection on the number of organisms recovered during ,bladder irrigation. Bacteria (from <100 to >1,000 organisms per ml.) were present in the urine of 47 per cent of patients immediately prior to bilateral nephrectomy and 43 per cent during subsequent bladder irrigation. Of those patients whose pre-nephrectomy culture was positive, 48 per cent had no bacteria during subsequent irrigation. Of those patients whose urine was initially sterile, 72 per cent remained so (fig. 1). Among the 15 patients with positive cultures both before nephrectomy and during irrigation, half had the same organism recovered from both studies (see table). Ejfect of bladder irrigation on post-transplantation infection. Eleven patients had no bladder irrigations during their anephric period while 54 patients were irrigated at least once with saline and neomycin sulfate solution, averaging 3 irrigations per patient, usually in a 1 to 2-week interval (fig. 2). During the post-transplant period of retention catheterization, half of the non-irrigated patients were bacteriuric compared to only a quarter of the irrigated patients (fig. 3). After removal of the catheter, both became bacteriuric in approximately the same proportion (73 vs. 79 per cent). Of the 30 patients with more significant subsequent infection, that is, with colony counts of
'47S
HINMAN AND BELZER
BACTERIAL RECOVERY DURING ANEPHRIC PERIOD
STERILE BEl=ORE NEPHRECTOMY
POSITIVE BEF'ORE NEPHRECTOMY Fm. 1
Relation of organisms in the pre-nephrectomy cultures to those recovered from bladder irrigations
No preceding infection: No organisms on irrigation Organisms on irrigation
17 8
Total 25 Preceding infection: No organisms on irrigation Organisms on irrigation
14 15 Total 29
Correlation between organisms: Present Absent
7 8
more than 1,000 per ml., 13 had had organisms recovered on irrigation. Of these, 7 had the same organism in both the irrigation fluid and in the post-transplant catheterization specimens. Ejfect of nephrectomy-transplant interval on bacteria from bladder irrigation. Delay in transplantation after nephrectomy did not increase the number of positive cultures during sequential bladder irrigations, which indicates that the duration of the anuria was not a factor (fig. 4). Relation of organisms after second transplantation to those after the first. Eight patients had a second renal transplant after failure and removal
of the first. Six of them had colony counts of more than 1,000 colonies per ml. after the second transplantation, compared to 2 patients after the first. Analysis of the types of organisms involved showed no correlation between the flora after the two procedures. Perhaps more significantly, whereas none of these patients had bacteriuria during the first period of retention catheterization, half of them had more than 1,000 organisms per ml. during the second catheterization period. DISCUSSION
Direct evidence for non-urinary defense mechanisms is limited, but is accumulating. Vivaldi and associates showed that bacteria are not recoverable if placed on the exposed vesical mucosa of the rabbit. 5 Norden and Kass placed radioactive bacteria in the bladders of female guinea pigs. 6 Although the animals promptly voided much of the inoculum, enough remained to determine that the total number of recoverable 5 Vivaldi, E., Munoz, J., Cotran, R. and Kass, E. H.: Factors affecting the clearance of bacteria within the urinary tract. In: Progress in Pyelonephritis. Edited by E. H. Kass. Philadelphia: F. A. Davis, Co., p. 531, 1965. . 6 Norden, C. W. and Kass, E. H.: Bladder antibacterial defense mechanisms. In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967.
URINARY TRACT INFECTION AND RENAL HOiVIO'TRANSPLANTATION.
ANUA.!C INTERVAL !N PA.Tl ENTS WITH AND WITI-IOUT BLADDER IRRIGATION
c::::J /3LADDE,Q !P.P.IGATIO/\l ($4 PATIENT.SJ
IBill'll NO l3LA0DE:.R
(II PAT/E.NTS
40
20
0
0-1
2-8
9-30
>30
DAYS INTERVAL BETWEEN NEPHRECTOMY AND TRANSPLANTATION
Fm. 2
E:l=FECT OF NEOMYCIN BLADDER IRRIGATIONS ON POST TRANSPLANTATION IN!=ECTION
NO 13LADOER IRRIGATION
WITH .RETENTION
CATHETER
CATHETER REMOVED
0
40
20 PER
CENT
60
PATIENTS
FIG. 3
80 iNF"ECTED
100
480
HINMAN AND BELZER
EFFECT OJ:" INTERVAL BETWEEN NEPHRECTOMY AND TRANSPLANTATION ON VESICAL BACTERIA 2-8
DAYS STERILE CULTURE
POSITIVE CULTURE
9-30
DAYS
>
i!SO
DAYS
0
40
20 PER
60
CENT
80
100
PATIENTS
FIG. 4
living bacteria was much lower than the radioactive count of the bladder. Calculating the percentage killed, it was shown that intrinsic defense mechanisms reduced the count by at least one log number in at least 4 hours. In some cases the reduction was by 2 and 2H log numbers. Other mechanisms such as bacterial clumping, effect of urinary constituents and phagocytosis did not play an important role. That bactericidal antibodies or bladder mucosal metabolites were active could only be speculated. Kay, in similar experiments, noted a slight decrease in radioactivity after 8 hours but a great decrease in the numbers of bacterial colonies. 7 By 24 hours both had decreased with half found in the cage or on the perineum of the rat and half in the animal itself. The mechanism of removal appeared to involve phagocytosis since bacteria were found adherent to the vesical mucosa in half an hour in quick-frozen specimens and white blood cells were always found on the mucosal surface by 4 hours. Furthermore, actual phagocytosis was seen. Drach and Cox were able to support this observation by finding immuno7 Kay, D.: Comments. In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967.
:fluorescence in white blood cells in the vesical submucosa in cases of cystitis due to Escherichia coli. 8 They suggested that these bacteria were either caught on the surface or were drawn through the mucosa by the phagocytes. Another defense mechanism, in male patients at least, may be the antibacterial activity of prostatic :fl.uid. 9 , 10 It has been suggested that ejaculatory movements at the end of voiding in the male patient may distribute the fluid in the urethra and bladder.11 Equivalent secretions have not been demonstrated m the female patient. That a resident flora exists m the normal urethra in both sexes has been well demonstrated.12 · 13 Its distribution is altered by many 8 Drach, G. W. and Cox, C. E.: Immunofluorescence studies of the bladder defense mechanism. I. Localization of Escherichia coli in the human bladder. J. Amer. Geriat. Soc., 16: 1114--1124, 1967. 9 Fair, W.R. and Stamey, T. A.: In: The Proceedings of a Workshop on Bacterial Infections of the Male Urogenital Tract. Washington, D. C.: National Research Council, 1967. 10 Gupta, S. N., Perkash, I., Agarwal, S. C. and Anand, S. S.: Antibacterial activity of human prostatic fluid. Invest. Urol., 6: 219, 1967. 11 Hinman, F., Jr.: Bacterial elimination. J. Urol., 99: 811-825, 1968. 12 Helmholz, H. F., Sr.: Determination of the bacterial content of the urethra: a new method,
URINARY TRACT INFECTION AND RENAL HOMOTRANSPLANTATION
poorly understood factors. One fact has emerged, however: pathogenic bacteria may establish themselves in the urethra prior to an attack of cystitis. 14 Perhaps the uremic state of transplant candidates alters the local urethral environment and allows redistribution and change of species. The experiments on dogs indicate that, at least if the urethra is manipulated by a catheter which may simultaneously introduce bacteria, the bladder is not protected against a certain, low resident flora. 3 Since these are the same circumstances surrounding the anephric phase of human transplantation, the findings have some practical relevance. However, the ability of the intrinsic vesical defenses to reject spontaneously introduced bacteria is not tested by these experiments, but experiments are being completed which avoid the urethral approach to culturing of the bladder contents and so may give a more direct answer. In human subjects, bacteriuria is not always perpetuated into the anephric period. (Among those bladders initially infected, 48 per cent were later sterile, although more than a quarter of the initially sterile bladders lost their sterility in the anephric period.) Adverse factors are often present in these patients, such as uremia and anemia, as well as the effects of urethral instrumentation. Instrumentation itself alters the distribution of the flora. 15 Since these transplant patients have all been catheterized and recatheterized, movement of bacterial populations may occur. No data are available to support this assumption, although Guttmann and Frankel's observation that repeated catheterization of 409 male patients who were not emptying their bladders because of neurogenic bladder did not produce infection in 64.8 per cent, suggests that instrumentation itself does not necessarily contaminate the bladder .16 with results of a study of 82 men. J. Urol., 64: 158-166, 1950.
13 Cox, C. E.: The urethra and its relationship to urinary tract infection: the flora of the normal female urethra. Southern Med. J., 59: 621, 1966. 14 Cox, C. E., Lacy, S.S. and Hinman, F., Jr.: The urethra and its relationship to urinary tract infection. II. The urethral flora of the female with recurrent urinary infection. J. Urol., 99: 632-638,
1968.
15 Drouin, G. and Hinman, F., Jr.: Unpublished observations. 16 Guttmann, L. and Frankel, H.: The value of
481
The immediate protective effect of antibacterial irrigation was seen when only a quarter of irrigated patients had bacteria during the immediate post-transplantation period while half the non-irrigated patients had bacteria. Later, after removal of the retention catheter and the opportunity provided for urethral bacteria to invade the bladder, the prior irrigations no longer exerted an effect. That no correlation exists between the duration of anuria and infection of the bladder suggests that defense factors either are or are not operative in any given case. The finding of an appreciably higher incidence of infection after a second homotransplant would indicate that the manipulations and medications attendant on repetition of the procedure weaken the bladder defenses and increase the opportunity for introduction of bacteria. SUMMARY AND CONCLUSIONS
Of 65 patients rendered anuric by bilateral nephrectomy prior to renal homotransplantation, 72 per cent of those initially sterile remained sterile during the period of anuria. If previously infected, 48 per cent were then sterile. Immediately after transplantation, threefourths of patients who had been given bladder irrigations with 1 per cent neomycin sulfate solution were sterile compared to one third of those not irrigated. However, later cultures after removal of the catheter showed no difference between the groups. The same organism persisted in half the patients with positive cultures obtained both during anuria and subsequently. Delay in transplantation did not increase the frequency of positive cultures during the anuric period. A second transplantation resulted in a much higher incidence of bacteriuria. The conclusion is reached that the normal vesicourethral defenses are greatly altered in the clinical anuric state, probably because of effects of uremia and repeated instrumentation of the lower urinary tract. Irrigation with antibacterial solutions transiently reduces the mc1dence of bacterial invasion of the bladder. intermittent catheterisation in the early management of traumatic paraplegia and tetraplegia. Paraplegia, 4: 63, 1966.