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Urinary Tract Infections Complicating Diabetes Mellitus
Urinary Tract Infections Complicating Diabetes Mellitus KEITH R. YOUNG, M.D. CARL F. CLANCY, PH.D.
URINARY tract infection has long been known to have an increased incidence in diabetes and to be a persistent and often serious complicating factor in the treatment of this disease. In an effbrtto survey the experience at the Pennsylvania Hospital in this respect, a two-part study was devised. Without attempting to duplicate the extent of the work of Bowen and Kutzman,l the following plan was undertaken.
METHODS USED IN THIS STUDY
The autopsy records of the Ayer Clinical Laboratory of the Pennsylvania Hospital for the ten year period from 1943 through 1952 were reviewed in association with the clinical records, and the findings in diabetics were compared with those of the population under study. During this period 1640 autopsies were conducted, of which 72 were on diabetics. In addition, a random group of 64 female diabetics being followed in the outpatient department was selected for questioning and for catheterization of the urinary bladder for a specimen for routine analysis and culture. The only departures from the random selection were in one case in which an anomalous urethral meatus precluded satisfactory catheterization, and in one in which the patient refused the procedure. These cases were therefore not included. The procedure was performed with strictest aseptic technique, and the specimens taken immediately to the laboratory. Cultures were planted on blood agar plates and incubated aerobically and anaerobically for primary isolation of organisms. Because of the possibility of carrying organisms into the bladder during the process of catheterization, a prophylactic course of Gantrisin, * 0.5 gram four times daily, was prescribed for two days following the procedure. A group of "normal" women was chosen from new admissions to the medical clinic and was similarly investigated. From the Medical Service of the Pennsylvania Hospital and the Ayer Clinical Laboratory, Philadelphia.
* The Gantrisin (sulfisoxazole) used in this study was provided through the courtesy of Hoffmann-LaRoche, Inc. 1665
Keith R. Young, Carl F. Clancy
1666
RESUI_TS
During the ten year period covered in the autopsy survey, 1640 examinations were conducted; the incidence of lesions resulting from infection of the urinary tract in this group is reported in Table 1. The autopsy Table 1 FINDINGS IN
1640
AUTOPSIES NO. OF CASES
Pyelonephritis. . . . . . . . . . . . . . . . . . . . . . . . Chronic cystitis. . . . . . . . . . . . . . . . . . Acute cystitis. . . . . . . . . . . . . . . . . . . . Multiple renal abscesses.. . . . . . . . . . . Perinephric abscess.. . . . . . . .. .............. Acute hemorrhagic cystitis. . . . . . . . . . . . . . . . . . Pyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cystitis cystica. . . . . . . . . .............. Bladder abscess. . . . . . . . . . Perinephritis. . . . . . . . . . . . .............. Necrotizing papillitis. . . . . . . ............. Urethritis. . . . . . . . . . . ..................
241 55 20 14 14 14 12 10 2 1 2 1
percentage for the years covered by these figures ranged between 59 and 70 per cent, while the over-all percentage for diabetics was 42 per cent. The summary of lesions for the latter group is contained in Table 2. An Table 2 FINDINGS IN AUTOPSIES ON
72
DIABETICS
(54
Chronic pyelonephritis ....... . Acute pyelonephritis ..... . Renal abscesses ................... . Perinephric abscesses ........ . Necrotizing papillitis ........ . Chronic cystitis ...... . Acute cystitis ............. . Urethritis ........................ .
FEMALES,
18
MALES)
FEMALES
MAI,ES
11 2 2 3 1 5 0 0
4 2 0 0 1 2 1 1
attempt was made to determine from the clinical records the incidence of symptoms, pyuria and positive urine cultures, but a number of unavoidable factors (inadequate history from the patient, history obtained only from patient's family, presence of indwelling catheter, etc.) in many cases made this estimation so incomplete that attempt~ at definite tabulation were abandoned. However, evaluation of those data which were available gave the impression that little if any correlation existed be-
Urinary Tract Infections Complicating Diabetes Mellitus
1667
tween these factors and evidence of pathologic change. The number of organic lesions detected at autopsy was 0.23 per examination in the total group, and 0.49 per examination for the diabetics. Subdivided by sexes, the corresponding figures for diabetics are 0.61 for males and 0.44 for females. Of the 62 diabetic females studied in the outpatient survey, 36 had negative cultures and 26 had one or more types of bacteria in their urine. Of these, eight had a pure culture of Corynebacterium nodosum and will be considered separately. A summary of the other data is presented in Tahle 3 FINDINGS IN
62
DIABETIC WOMEN
Symptoms .............................. . Pregnancies delivered None ................................ . 1~3 ................................ . Over 3 ............................... . Previous catheterizations ................. . Pyuria Mild ................................. . Heavy ............................... . Clumps ...................... . Albuminuria 1 to 2 plus ................. . 3 to 4 plus ................... .
NEGATIVE CULTURE
C. NODOSUM
OTHER ORGANISMS
10
2
4
9 11 16 10
2 2 4 2
5 6 7 3
4
5 4 4
14
o 3
2
o
o
o
o
1
o
o
Tahle 4 INFECTING ORGANISMS IN
18
POSITIVE CULTURES (EX.CLUDING C. NODOSUM)
Escherichia coli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Aerobacteria aerogenes and other coJiforms. . . . . . . .. Unidentified gram-positive bacilli.. . . . . . . . . . . . . . . .. Clostridium tertium. . . . . . . . . . . . . . . . . . . . . . . . . . . .. Streptococcus faecalis. . . . . . . .. ................. N onhemolytic streptococcus. . . . . . . . . . . . . . . . . . . Beta hemolytic streptococcus. . . . . . . . . . . . . . . . . . . ..
8 7 5 1 1 1 1
Table 3. Nocturia of at least one time nightly was a nearly universal complaint and for that reason is not included in the tabulation of other symptoms, chiefly transient dysuria or mild frequency. The data on previous catheterizations are probably in error in many cases, since this procedure was undoubtedly carried out in many of the obstetrical deliveries which these patients had undergone. All patients denied any history of recent antibiotic or chemotherapeutic medication. The organisms isolated in culture of the urine of 18 of these patients are listed in Table 4. The remaining eight patients were found to harbor
Keith R. Young, Carl F. Clancy
1668
C. nodosum, described by Eberson 2 as a nonpathogenic diphtheroid, an inhabitant of the normal urethra. In addition, this organism was found in the urine of two of the patients who also had pathogens. A summary of the clinical findings in the patients from whom C. nodosum was recovered is included in Table :3. Twenty nondiabetic women were selected at random from medical clinic admissions and subjected to similar evaluation, the results appearing in Table 5. The symptomatology in this group was practically idenTable 5 FINDINGS IN
20 N ONDIABE'l'IC
WOMEN
NEGATIVE CULTURE
Symptoms .. Pregnancies delivered None ....... . 1 to 3.... ...... .. Over 3 ...... . Previous catheterizations ... Pyuria Mild .. Heavy. Clumps .. Albuminuria 1 to 2 plus. 3 to 4 plus .....
5
POSITIVE CULTURE
---0
3 7 9
0 1 0 0
8 I
3
2 0 0
0 0
1 0
6
tical to that of the diabetic group. One patient was excluded from the control group when she was found to be diabetic, and another who had had penicillin four days earlier was not included. Two of the 20 patients were shown to have urinary tract infection, one with beta hemolytic streptococci, and the other with both nonhemolytic streptococci and C. nodosum. ILLUSTRATIVE CASES
In order to emphasize the extreme gravity of urinary tract infections in diabetics as well as the importance of their early detection and eradication, brief abstracts from two contrasting clinical records are presented. CASE 1. A 51 year old white woman was admitted with a history of known diabetes of 10 years' duration and periodic episodes of right costovertebral pain with fevel'. The current illness had begun 2 days prior to admission with right flank pain, vomiting, fever and chills. The patient had become progressively stuporous up to the time of admission. Findings on admission included temperature of 101 0 F., pulse rate 128, and respirations 34, moderate dehydration, tenderness of the right upper quadrant, and a questionably palpable mass in this region. The white blood cell count was 25,000 per cu. mm., and the urine
Urinary Tract Infections Complicating Diabetes Mellitus
1669
contained 1 plus sugar, no acetone, 3 plus albumin, and many white blood cells. The blood sugar was 450 mg. per 100 cc., and the CO 2 combining power was 16.2 mEq. per liteI'. Cultures of urine and blood both revealed E. coli organisms. The diabetes was controlled with a program of regular insulin. 3 Pending the return of the results of cultures and sensitivity studies, the patient was treated with sulfadiazine, but when reports indicated that the organism was sensitive to streptomycin, therapy was changed to this antibiotic. Under this program the blood and urine became sterile, but the patient's condition failed to improve and she died on her twentieth hospital day. Findings at autopsy disclosed pyelonephritis with multiple cortical and perinephric abscesses from which E. coli organisms were recovered. In addition there were two areas of abscess formation in the left cerebral hemisphere. CASE n. A 48 year old Negro woman was admitted with a history of mild diabetes and one week of dysuria, frequency, urgency and nocturia, accompanied by pain and tenderness in the left flank and suprapubic areas. Except for a temperature of 1040 F., the physical findings on admission were not remarkable. The white blood cell count was 9800 per cu. mm., and the urinalysis disclosed 4 plus sugar, 3 plus acetone, a trace of albumin, and many white blood cells in the sediment. A culture of the urine revealed E. coli organisms. Therapy was begun immediately with Gantrisin, penicillin and streptomycin, and the diabetes was controlled with regular insulin. 3 On the basis of sensitivity studies the antibiotic therapy was changed to tetracycline, and on the fourth hospital day the urine became sterile, and the patient was afebrile. She was discharged in good health on her eighth hospital day, at which time her diabetes was controlled on diet alone. DISCUSSION
From the data included in Table 3 it is apparent that no absolute dependence can be placed on either symptomatology or the finding of pyuria in a case-finding program of this type. Onc may contend that lack of leukocytic response indicates lack of pathogenicity, but the incidence of organic change as discovered at autopsy would seem to indicate otherwise. While it is not practical to obtain periodic catheterized urine specimens from all diabetics, one is nevertheless obliged to maintain a careful watch for symptoms, signs and laboratory evidence of urinary tract infection when these do appear. Although no evidence is presented to substantiate it, it seems reasonable to assume that periodic rechecks might disclose pyuria when a single specimen fails to do so. The study of "clean washed" voided specimens is urged whenever possible, and in cases where catheterization cannot be avoided, a careful technique similar to that outlined by Barnard et al.,4 together with prophylactic chemotherapy, is highly desirable. It seems warranted to re-emphasize the point presented by Barnard and his associates4 with regard to instruction of the female diabetic in proper means of cleansing the perineum after defecation, so that fecal contamination will be wiped away from, rather than toward, the urinary meatus.
1670
Keith R. Young, Carl F. Clancy
Therapy is based on good diabetic control, which is discussed elsewhere in this symposium, and on the use of specific antibiotics as determined by sensitivity tests. While awaiting the results of such studies, one can often be guided in choice of interim therapy by study of the stained urinary sediment, although usually a sulfonamide, such as Gantrisin, is suitable. SUMMARY
Data concerning urinary tract infections in diabetics have been collected from an autopsy study and a clinical survey, and presented in tabular form. Discussion of the significance of the results, together with case abstracts, has been brought forward to stress the importance of constant vigilance, careful prophylaxis, and effective therapy. REFERENCES 1. Bowen, B. D. and Kutzman, N.: The Urinary Tract in Diabetic Women; Its Contribution to the Incidence of Hypertension. Ann. Int. Med. 17: 427, 1942. 2. Eberson, F.: A Bacteriologic Study of the Diphtheroid Organisms with Special Reference to Hodgkin's Disease. J. Infect. Dis. 23: 4, 1918. 3. Duncan, G. G.: Diabetes Mellitus. Philadelphia, W. B. Saunders Co., 1951. 4. Barnard, D. M., Story, R. D. and Root, H. F.: Urinary Tract Infections in Diabetic Women. New England J. Med. 248: 136, 1953.
Pennsylvania Hospital 8th and Spruce Streets Philadelphia 5, Pennsylvania
URINARY tract infection has long been known to have an increased incidence in diabetes and to be a persistent and often serious complicating factor in the treatment of this disease. In an effbrtto survey the experience at the Pennsylvania Hospital in this respect, a two-part study was devised. Without attempting to duplicate the extent of the work of Bowen and Kutzman,l the following plan was undertaken.
METHODS USED IN THIS STUDY
The autopsy records of the Ayer Clinical Laboratory of the Pennsylvania Hospital for the ten year period from 1943 through 1952 were reviewed in association with the clinical records, and the findings in diabetics were compared with those of the population under study. During this period 1640 autopsies were conducted, of which 72 were on diabetics. In addition, a random group of 64 female diabetics being followed in the outpatient department was selected for questioning and for catheterization of the urinary bladder for a specimen for routine analysis and culture. The only departures from the random selection were in one case in which an anomalous urethral meatus precluded satisfactory catheterization, and in one in which the patient refused the procedure. These cases were therefore not included. The procedure was performed with strictest aseptic technique, and the specimens taken immediately to the laboratory. Cultures were planted on blood agar plates and incubated aerobically and anaerobically for primary isolation of organisms. Because of the possibility of carrying organisms into the bladder during the process of catheterization, a prophylactic course of Gantrisin, * 0.5 gram four times daily, was prescribed for two days following the procedure. A group of "normal" women was chosen from new admissions to the medical clinic and was similarly investigated. From the Medical Service of the Pennsylvania Hospital and the Ayer Clinical Laboratory, Philadelphia.
* The Gantrisin (sulfisoxazole) used in this study was provided through the courtesy of Hoffmann-LaRoche, Inc. 1665
Keith R. Young, Carl F. Clancy
1666
RESUI_TS
During the ten year period covered in the autopsy survey, 1640 examinations were conducted; the incidence of lesions resulting from infection of the urinary tract in this group is reported in Table 1. The autopsy Table 1 FINDINGS IN
1640
AUTOPSIES NO. OF CASES
Pyelonephritis. . . . . . . . . . . . . . . . . . . . . . . . Chronic cystitis. . . . . . . . . . . . . . . . . . Acute cystitis. . . . . . . . . . . . . . . . . . . . Multiple renal abscesses.. . . . . . . . . . . Perinephric abscess.. . . . . . . .. .............. Acute hemorrhagic cystitis. . . . . . . . . . . . . . . . . . Pyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cystitis cystica. . . . . . . . . .............. Bladder abscess. . . . . . . . . . Perinephritis. . . . . . . . . . . . .............. Necrotizing papillitis. . . . . . . ............. Urethritis. . . . . . . . . . . ..................
241 55 20 14 14 14 12 10 2 1 2 1
percentage for the years covered by these figures ranged between 59 and 70 per cent, while the over-all percentage for diabetics was 42 per cent. The summary of lesions for the latter group is contained in Table 2. An Table 2 FINDINGS IN AUTOPSIES ON
72
DIABETICS
(54
Chronic pyelonephritis ....... . Acute pyelonephritis ..... . Renal abscesses ................... . Perinephric abscesses ........ . Necrotizing papillitis ........ . Chronic cystitis ...... . Acute cystitis ............. . Urethritis ........................ .
FEMALES,
18
MALES)
FEMALES
MAI,ES
11 2 2 3 1 5 0 0
4 2 0 0 1 2 1 1
attempt was made to determine from the clinical records the incidence of symptoms, pyuria and positive urine cultures, but a number of unavoidable factors (inadequate history from the patient, history obtained only from patient's family, presence of indwelling catheter, etc.) in many cases made this estimation so incomplete that attempt~ at definite tabulation were abandoned. However, evaluation of those data which were available gave the impression that little if any correlation existed be-
Urinary Tract Infections Complicating Diabetes Mellitus
1667
tween these factors and evidence of pathologic change. The number of organic lesions detected at autopsy was 0.23 per examination in the total group, and 0.49 per examination for the diabetics. Subdivided by sexes, the corresponding figures for diabetics are 0.61 for males and 0.44 for females. Of the 62 diabetic females studied in the outpatient survey, 36 had negative cultures and 26 had one or more types of bacteria in their urine. Of these, eight had a pure culture of Corynebacterium nodosum and will be considered separately. A summary of the other data is presented in Tahle 3 FINDINGS IN
62
DIABETIC WOMEN
Symptoms .............................. . Pregnancies delivered None ................................ . 1~3 ................................ . Over 3 ............................... . Previous catheterizations ................. . Pyuria Mild ................................. . Heavy ............................... . Clumps ...................... . Albuminuria 1 to 2 plus ................. . 3 to 4 plus ................... .
NEGATIVE CULTURE
C. NODOSUM
OTHER ORGANISMS
10
2
4
9 11 16 10
2 2 4 2
5 6 7 3
4
5 4 4
14
o 3
2
o
o
o
o
1
o
o
Tahle 4 INFECTING ORGANISMS IN
18
POSITIVE CULTURES (EX.CLUDING C. NODOSUM)
Escherichia coli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Aerobacteria aerogenes and other coJiforms. . . . . . . .. Unidentified gram-positive bacilli.. . . . . . . . . . . . . . . .. Clostridium tertium. . . . . . . . . . . . . . . . . . . . . . . . . . . .. Streptococcus faecalis. . . . . . . .. ................. N onhemolytic streptococcus. . . . . . . . . . . . . . . . . . . Beta hemolytic streptococcus. . . . . . . . . . . . . . . . . . . ..
8 7 5 1 1 1 1
Table 3. Nocturia of at least one time nightly was a nearly universal complaint and for that reason is not included in the tabulation of other symptoms, chiefly transient dysuria or mild frequency. The data on previous catheterizations are probably in error in many cases, since this procedure was undoubtedly carried out in many of the obstetrical deliveries which these patients had undergone. All patients denied any history of recent antibiotic or chemotherapeutic medication. The organisms isolated in culture of the urine of 18 of these patients are listed in Table 4. The remaining eight patients were found to harbor
Keith R. Young, Carl F. Clancy
1668
C. nodosum, described by Eberson 2 as a nonpathogenic diphtheroid, an inhabitant of the normal urethra. In addition, this organism was found in the urine of two of the patients who also had pathogens. A summary of the clinical findings in the patients from whom C. nodosum was recovered is included in Table :3. Twenty nondiabetic women were selected at random from medical clinic admissions and subjected to similar evaluation, the results appearing in Table 5. The symptomatology in this group was practically idenTable 5 FINDINGS IN
20 N ONDIABE'l'IC
WOMEN
NEGATIVE CULTURE
Symptoms .. Pregnancies delivered None ....... . 1 to 3.... ...... .. Over 3 ...... . Previous catheterizations ... Pyuria Mild .. Heavy. Clumps .. Albuminuria 1 to 2 plus. 3 to 4 plus .....
5
POSITIVE CULTURE
---0
3 7 9
0 1 0 0
8 I
3
2 0 0
0 0
1 0
6
tical to that of the diabetic group. One patient was excluded from the control group when she was found to be diabetic, and another who had had penicillin four days earlier was not included. Two of the 20 patients were shown to have urinary tract infection, one with beta hemolytic streptococci, and the other with both nonhemolytic streptococci and C. nodosum. ILLUSTRATIVE CASES
In order to emphasize the extreme gravity of urinary tract infections in diabetics as well as the importance of their early detection and eradication, brief abstracts from two contrasting clinical records are presented. CASE 1. A 51 year old white woman was admitted with a history of known diabetes of 10 years' duration and periodic episodes of right costovertebral pain with fevel'. The current illness had begun 2 days prior to admission with right flank pain, vomiting, fever and chills. The patient had become progressively stuporous up to the time of admission. Findings on admission included temperature of 101 0 F., pulse rate 128, and respirations 34, moderate dehydration, tenderness of the right upper quadrant, and a questionably palpable mass in this region. The white blood cell count was 25,000 per cu. mm., and the urine
Urinary Tract Infections Complicating Diabetes Mellitus
1669
contained 1 plus sugar, no acetone, 3 plus albumin, and many white blood cells. The blood sugar was 450 mg. per 100 cc., and the CO 2 combining power was 16.2 mEq. per liteI'. Cultures of urine and blood both revealed E. coli organisms. The diabetes was controlled with a program of regular insulin. 3 Pending the return of the results of cultures and sensitivity studies, the patient was treated with sulfadiazine, but when reports indicated that the organism was sensitive to streptomycin, therapy was changed to this antibiotic. Under this program the blood and urine became sterile, but the patient's condition failed to improve and she died on her twentieth hospital day. Findings at autopsy disclosed pyelonephritis with multiple cortical and perinephric abscesses from which E. coli organisms were recovered. In addition there were two areas of abscess formation in the left cerebral hemisphere. CASE n. A 48 year old Negro woman was admitted with a history of mild diabetes and one week of dysuria, frequency, urgency and nocturia, accompanied by pain and tenderness in the left flank and suprapubic areas. Except for a temperature of 1040 F., the physical findings on admission were not remarkable. The white blood cell count was 9800 per cu. mm., and the urinalysis disclosed 4 plus sugar, 3 plus acetone, a trace of albumin, and many white blood cells in the sediment. A culture of the urine revealed E. coli organisms. Therapy was begun immediately with Gantrisin, penicillin and streptomycin, and the diabetes was controlled with regular insulin. 3 On the basis of sensitivity studies the antibiotic therapy was changed to tetracycline, and on the fourth hospital day the urine became sterile, and the patient was afebrile. She was discharged in good health on her eighth hospital day, at which time her diabetes was controlled on diet alone. DISCUSSION
From the data included in Table 3 it is apparent that no absolute dependence can be placed on either symptomatology or the finding of pyuria in a case-finding program of this type. Onc may contend that lack of leukocytic response indicates lack of pathogenicity, but the incidence of organic change as discovered at autopsy would seem to indicate otherwise. While it is not practical to obtain periodic catheterized urine specimens from all diabetics, one is nevertheless obliged to maintain a careful watch for symptoms, signs and laboratory evidence of urinary tract infection when these do appear. Although no evidence is presented to substantiate it, it seems reasonable to assume that periodic rechecks might disclose pyuria when a single specimen fails to do so. The study of "clean washed" voided specimens is urged whenever possible, and in cases where catheterization cannot be avoided, a careful technique similar to that outlined by Barnard et al.,4 together with prophylactic chemotherapy, is highly desirable. It seems warranted to re-emphasize the point presented by Barnard and his associates4 with regard to instruction of the female diabetic in proper means of cleansing the perineum after defecation, so that fecal contamination will be wiped away from, rather than toward, the urinary meatus.
1670
Keith R. Young, Carl F. Clancy
Therapy is based on good diabetic control, which is discussed elsewhere in this symposium, and on the use of specific antibiotics as determined by sensitivity tests. While awaiting the results of such studies, one can often be guided in choice of interim therapy by study of the stained urinary sediment, although usually a sulfonamide, such as Gantrisin, is suitable. SUMMARY
Data concerning urinary tract infections in diabetics have been collected from an autopsy study and a clinical survey, and presented in tabular form. Discussion of the significance of the results, together with case abstracts, has been brought forward to stress the importance of constant vigilance, careful prophylaxis, and effective therapy. REFERENCES 1. Bowen, B. D. and Kutzman, N.: The Urinary Tract in Diabetic Women; Its Contribution to the Incidence of Hypertension. Ann. Int. Med. 17: 427, 1942. 2. Eberson, F.: A Bacteriologic Study of the Diphtheroid Organisms with Special Reference to Hodgkin's Disease. J. Infect. Dis. 23: 4, 1918. 3. Duncan, G. G.: Diabetes Mellitus. Philadelphia, W. B. Saunders Co., 1951. 4. Barnard, D. M., Story, R. D. and Root, H. F.: Urinary Tract Infections in Diabetic Women. New England J. Med. 248: 136, 1953.
Pennsylvania Hospital 8th and Spruce Streets Philadelphia 5, Pennsylvania