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Salmonella Infections of the Kidney
Vol. 94, .July Printed 1·n T].S.A.
TttE .JocRNAL oF UROLOGY
Copyright© l965 by The Williams & VVilkins Co.
SAL~\IONELLA INFECTIONS OF THE KIDNEY M. MELZER, G. ALT.MA.KN, M. RAKOWSZCYK, Z. H. YOSIPOYITCH
,IKD
B. BARSILAI
From the Departments of Urology ancl Bacteriology, Government Hospital Tei-Hashomer, Tel-Aviv ancl the Department of Urology, Hebrew University-Haclcrnsah Medical School, Jerusalem, Israel
The patient had been an inmate of a concentration camp in 1942. She contracted typhoid fever and became a carrier of the disease. For approximately 5 years prior to her admission she had recurrent episodes of urinary tract infection which usually responded to chloramphenicol. On admission in 1955 an abscess near the right iliac crest was detected and found to be connected to the right urinary tract. Sal. typhi was isolated from pus from the perinephric abscess as well as from the urine. X-rays of the chest and the spine demonstrated old, healed tuberculous processes of both lungs. The Dll vertebra had collapsed. An excretory urogram revealed the right kidney to be small and not excreting. Hydronephrosis and hydrometer were noted on the left side. Cystoscopy showed a contracted bladder. The ureteral orifices could not be identified. Cystography demonstrated bilateral reflux (fig. 1). Despite treatment with chloramphenicol and other antibiotics, the patient's condition slowly deteriorated. Urine cultures were consistently positive for Sal. typhi, except for periods when large doses of chloramphenicol were administered. Urine cultures for tuberculosis were twice negative. Death in May 1956 was due to shock. Postmortem examination disclosed caseous tuberculosis of the left kidney. The right kidney was completely destroyed by multiple abscesses which reached down to the fistula near the right iliac crest. Abscesses consisting of tuberculoid granulation tissue were found in the pancreas. Case 2. B. F., a 38-year-old wmnan, was admitted to the hospital in 1954 with fever, weakness and pains in the loin. Typhoid fever was suspected; the ·widal reaction test was positive, 1/100 for Sal. typhi O and H. The patient was treated with chloramphenicol. Blood sedimentation rate was 90/127 mm. Blood and urine cultures were sterile. The urine contained album.in and many leukocytes. An excretory urogram. revealed a normal right kidney. The left kidney showed some calcification and weak and delayed excretion. No pathological changes were seen
During an attack of typhoid fever the causative organisms are found during the acute stage of the disease in the bloodstream, bone marrow, spleen and biliary system. The kidneys are usually not involved, but statistics indicate that before the introduction of chloramphenicol for the treatment of typhoid fever, 20 to 40 per cent of patients excreted Salmonella in the urine, usually during the second or third week of the disease. As the passage of bacteria through the intact kidney is not probable, bacilluria in typhoid fever is explained by toxic nephrosis1 or by the formation of micro-abscesses or metastatic foci in the kidney. These lesions disappear during convalescence in the majority of patients. In persons with pre-existing pathological changes such as nephrolithiasis, 2 • 3 hydroncphrosis, anatomical anomaly or, especially in endemic areas like Egypt, urinary schistosomiasis, 4 • 5 the Salmonella organis1ns establish themselves in the damaged tissue and produce chronic infection. A perinephric abscess may develop if the bacteria penetrate into the perinephrium; or pyelonephritis results, bacteria are shed constantly in the urine and the patient becomes a urinary carrier. The epidemiological importance of permanent urinary excreters of Salrn.onella is well documented and need not to be elaborated further. As infections of the kidneys clue to Salmonella and their treatrn.ent are of interest to the clinician as well as to the epidemiologist, the case histories of the following 10 patients who came to our attention from. 1952 to 1959 are presented. CASE REPORTS
Primary damage: tuberculosis of kidney Case 1, P. K., a 63-year-old woman, was born in Romania and had lived for 6 years in IsraeL
Accepted for publication November 10, 1964. 1 Bumke, E.: Yirchow's Arch., 256: 446, 1925. 2 Patch, F. S.: Typhoid infection of the kidney. J. Urol., 14: 199, 1925. 3 Dreyfuss, F. and Hoth, J.: Typhoid bacilluria and urolithiasis. Amer. J. Med. Sci., 210: 591, 1945. 4 Neva, F. A.: Urinary enteric carriers in Egypt. Amer. J. Trop. Med., 29: 909, 1949.
5 Miller, W. S. and Floyd, T. M. Chronic urinary Salmonella carriers. Lancet, 1: 343, 1954.
23
24
MELZER AND ASSOCIATES
Fm. 1. Case 1. Cystography demonstrating bilateral reflux. in the bladder. Left retrograde pyelography demonstrated reflux connected to a cavity. Urine was collected for cultures and guinea pig inoculation. Triple-drug treatment was started. An excretory urogram, taken 3 months later, showed the left kidney to be displaced and the shadow of the psoas obscured (fig. 2). The patient was operated on and a perinephric abscess was found. The kidney was displaced laterally and downwards. Pus taken from the abscess grew Sal. typhi. Cultures and guinea pig inoculation from urine taken before operation were positive for Mycobacterium tuberculosis. A sinus developed at the site of the incision. Pus obtained from this sinus yielded Sal. typhi for 2 months. Urine and stool cultures were negative. The patient disclosed that 14 years ago she had had typhoid fever. Despite tripledrug treatment the tuberculous process in the kidney progressed as shown by an excretory urogram. A left nephrectomy was performed. Histological examination of the kidney showed tuberculoid reaction on the tip of the papillae and peripelvic tissue and acid-fast bacilli could be demonstrated. Recovery was uneventful. Urine cultures taken up to the year 1963 were negative both for Sal. typhi and Mb. tuberculosis.
Case 3. M. H. B., a 14-year old boy, born in Yemen, was adn1itted to the hospital in 1954 with fever, rigor and bloody urine. The liver and spleen were enlarged. The urine contained many erythrocytes and leukocytes. His parents told of numerous attacks of hematuria in the past. Cystolithotomy was probably performed when the boy was 6 years old. There was no history of typhoid fever. An excretory urogram revealed the left kidney to be completely calcified and non-functioning. Good excretion was present on the right side but many calculi were seen in the calyces (fig. 3). Urine cultures grew Sal. typhi. Repeated stool cultures were negative. The patient ·was treated with chloramphenicol, 1 gm. a day. The fever subsided and urine cultures became negative. Two months later he was re-admitted with similar complaints. Urine cultures were again positive for Sal. typhi. He was again treated with chlorarnphenicol and becarn.e afebrile. After his discharge from hospital the patient did not return for followup examinations. Three years later he underwent a left nephrectomy elsewhere. Histological examination of the kidney showed a tuberculous process. In 1960 a cold abscess on the side of the operation was incised and in 1961, incision and drainage of a periurethral abscess were accomplished. One urine culture in 1962 was negative; however, a urine specimen obtained a year later grew Sal. typhi. This patient continues to pass Salmonella in the urine, 10 years after his carrier state was first detected. Case 4. Ch. A., a 30-year-old man, born in
Fm. 2. Case 2. Excretory urogram shows lateral displacement of left kidney. Shadow of psoas obscured.
SALMONELLA INFECTIONS OF KIDNEY
I
'j I
Fw. 3. Case 3. Excretory urogram shows calcified left kidney. Calculi in calyces of right kidney.
I I
Yemen, was admitted to the hospital in 1956 with left renal colic and fever. His illness had started 4 months ago. On admission he was undernourishecl. ]'darked tenderness ,Yas noted on percussion of the left kidney. An excretory urogram showed a normally excreting right kidney. The pelvis and calyces of the left kidney were filled with calculi and excretion was markedly reduced. Left retrograde pyelography revealed an enlarged pelvis and obstruction of rn.ost calyces (fig. 4). Despite treatment with chloramphenicol and streptomycin, urine cultures repeatedly yielded Sal. typhimurium. Stool cultures were negative. The patient was readmitted with the same complaints a month later and again he was treated with antibiotics without success. Therefore, a left nephrectom.y was performed. Chloramphenicol was given as a prophylactic measure. Histological examination of the kidney showed caseous tuberculosis. Recovery was uneventful and the patient was put on triple antituberculous therapy. Repeated urine cultures postoperatively were negative.
25
tions were positive for Sal. typhi O and m a titer of 1 /100. An excretory urogram revealed an enlarged, calcified, non-excreting left kidney with calculi. The shadow of the psoas muscle was obscured by a mass reaching down to the iliac crest. The right kidney was normal. CystoRcopy revealed a normal bladder, but the left ureteral orifice could not be identified. At operation, a large abscess, enclosed by a fibrotic capsule, containing 1200 ml. pus, was found. The abscess connected with the lower pole of the left kidney. The abscess was drained, extirpated and nephrectomy was performed. Cultures of pus from. the abscess as well as that taken from the pelvis of the kidney grew Sal. typhi. Histological examination showed pyohyclronephrosis with stones and a bifid pelvis. The kidney parenchyma was destroyed and transform.eel to a thin fi brotic layer. Recovery was uneventful. Urine cultures were negative 3 years later. The patient told of having had typhoid fever 11 years ago. Case 6. D. A., a 24-year-old woman, born in Yemen, was admitted to the hospital in 1959 with urinary tract infection 4 years in duration. There was no history of typhoid fever. An excretory urogram disclosed a ptotic, excreting right kidney. Calculi were present in the left kidney and no excretion was visualized. Left retrograde pyelography disclosed that the kidney was obstructed by calculi. Urine cultures grew Sal. typhi. Stool cultures were negative. A urine specimen ob-
Primary damage: nephrolithiasis Case 5. Z. E., a 22-year-old woman, was admitted to the hospital in 1954 with fever, rigor and pains in the left upper abdomen, where a mass could be palpated. Urine specimens contained traces of album.in and some pus cells. Cultures grew Staphylococcus aureus and were negative for Salmonella and JVIb. tuberculosis. The leukocyte count was 15,000 and the blood sedimentation rate was 56 mm. the first hour. Serum agglutina-
Fm. 4. Case 4. Left retrograde pyelography demonstrates an enlarged pelvis with obstructed calyces.
26
MELZER AND ASSOCIATES
tained by ureteral catheter from the right (normal) kidney was sterile. Results of the Widal test were as follows: Sal. typhi, 0, positive 1/100; Sal. typhi, H, positive 1/400. No Vi agglutination was performed. A left nephrectomy was accomplished. Chloramphenicol was given as a prophylactic measure. Urine specimens taken during operation from the left pelvis again grew Sal. typhi. Pathological examination showed the kidney to be completely destroyed by pyelonephritis due to calculous obstruction. Urine cultures postoperatively were negative. In this patient it was possible to prove that the infection by Sal. typhi was localized in the diseased kidney. Case 7. B. R., a 33-year-old woman, born in Tripoli, was admitted to the hospital in 1955 with pains in the loins, fever and a blood urea of 90 mg. per cent. An excretory urogram showed a small calculus in the pelvis of the left kidney with good excretion. The right kidney showed a staghorn calculus and was non-excreting. There were no pathological changes in the bladder. Urine cultures were positive for Sal. typhi. Stool cultures were negative. Treatment with chloramphenicol, 1 gm. per day, was started and sulfadiazine ·and nitrofurantoin were given later. Urine cultures during treatment became negative. Serum agglutination was Sal. typhi, 0, negative 1/100; Sal. typhosa, H, positive, 1/400; and Vi, positive, 1/40. The patient was readmitted 2 months later. Her left ureter was found to be obstructed by the calculus which had descended from the pelvis to the mid-ureter. A left ureterolithotomy was performed. Recovery was uneventful and postoperative urine cultures were negative. A year later the patient was admitted for curettage. Sal. typhi was again cultured from the urine. Stool cultures were negative. This pointed to the right kidney as the source of Sal. typhi. Retrograde pyelography confirmed earlier findings and a right nephrectomy was performed. Histological examination of the kidney showed destruction due to calculi and chronic pyelonephritis. Urine cultures 2 years postoperatively were negative. Case 8. T. R., an 18-year-old boy, born in Tripoli, was first admitted to the hospital in 1955 with pains in the loins and hematuria. An excretory urogram demonstrated multiple calculi in the right upper calyx and on the left side, a
stricture of the ureteropelvic junction with hydronephrosis. Function was present in both kidneys. The patient left the hospital on his own request before the investigation could be completed. He was admitted to different hospitals for the same complaints during the next few years. In 1962 he was readmitted to our hospital with the same finding'S. Repeated urine cultures were positive for Sal. typhi. Stool cultures and cultures from duodenal contents were negative. Cholecystography was normal. Left pyeloplasty was performed. Urine cultures during the ensuing year after operation grew Pseudomonas aeruginosa and Escherichia coli, but were negative for Sal. typhi. As the patient is under continuous antibiotic treatment, it is too early to decide whether the Sal. typhi infection has responded to therapy. Case 9. S. B., a 28-year-old woman, was admitted in 1955 with pollakiuria, dysuria and pains in the loin of 1 year's duration. An excretory urogram showed right hydronephrosis due to a calculus in the pelvis and two small calculi in the calyces. The left kidney was normal. The urine contained many pus cells and repeated cultures grew Sal. typhi. Separate urine specimens obtained from the left and right kidney grew Sal. typhi from the right side only. Cultures from the left kidney were sterile. The patient said that she had had typhoid fever 12 years ago. She was treated with 15 gm. chloramphenicol for 10 days. Urine cultures taken after treatment were again positive. Right nephrotomy was performed and recovery was uneventful. She was seen in our outpatient department several times until 1962. All urine cultures were negative for Sal. typhi. Case 10. H. B., a 44-year-old woman, underwent a left pyelolithotomy in 1949. She was admitted to the hospital in 1952 with bilateral nephrolithiasis and hydronephrosis. The urine contained albumin and many leukocytes. Cultures grew Sal. typhi. She had had typhoid fever 10 years before. A right nephrolithotomy and partial nephrectomy were performed and multiple stones were removed. Histological examination of the removed tissue revealed chronic and acute pyelonephritis. It was possible to grow Sal. typhi from a calculus. Urine cultures after operation were again positive for Sal. typhi. The patient was again hospitalized 2 years later and a left nephrolithotorn.y was performed. Bilateral hydronephrosis is still present and the
27
SALMONELLA INFECTIONS OF KIDNEY
right kidney is apparently contracting. The patient is under continuous antibiotic treatment. Although cultures taken after the second operation were negative for Sal. typhi, it is not yet possible to state whether the infection finally responded to therapy. DISCUSSION
To the pre-existing diseases favoring infection of Sahnonella, tuberculosis of the kidney should be added, ,vhich was found (with or without nephrolithiasis) in four of our patients. This combination has been described only once 6 but should be looked for in every case of Salmonella infection of the urinary tract. All our patients had serious obstructive disease of the kidney. In three a perinephric abscess had developed from which Sal. typhi was isolated. In two of these, tuberculosis of the kidney was apparently the primary damage. The long interval (11 to 14 years) between the attack of typhoid fever and the first symptoms of the perinephric abscess is noteworthy. Perinephric abscess due to Salmonella is a rare entity and probably not more than four bacteriologically proved cases have been describecl.7 Salmonella reaches the kidneys by the hematogenous route and apparently both kidneys are originally infected. The infection persists on one side only, if the pathological changes are restricted to one kidney. That the infection was unilateral could be shown indirectly in 2 patients who ceased to excrete the causative organism in the urine after nephrectomy and in 2 patients with perinephric abscess. In 2 patients (cases 6 and 9) it was possible to prove that the infection was unilateral by examining urine samples from 6 Veelken, D.: Typhuspyonephrose in Kombination mit Nierentuberkulose und Nierenstcin. Zeit Urol., 5~: 721, 1961. 7 Yosipovitch, Z. H.· Typhoid perinephric abcess. Thesis: The Hebrew University Hadassah Medical School, Jerusalem, 1957.
the left and right kidney separately, On the other hand one patient (case 3) with bilateral kidney damage, on whom nephrectomy was perform.eel 3 years after Sal. typhi was first detected in the urine, continued to excrete bacteria intermittently and his last positive culture was obtained 7 years after operation. Long folluwup periods and repeated cultures are necessary till a carrier can be declared as cleared, if damage of the kidney still persists. Although all patients who excreted Salmonella were treated with chloramphenicol, tetracycline, streptomycin and nitrofurantoin for relatively long periods and ceased to excrete the organism during treatment, all yielded positive cultures again after antibiotics were cliscontinuecL Only surgical removal of the diseased kidney or the obstruction terminated the Sahnonella carrier state. Recent trials ·with ampicillin point to the possibility that certain carriers may be cleared with high doses and prolonged treatment with this new semi-synthetic penicillin. 8 SUMMARY
A report of 10 patients with chronic infection of the kidney due to Salmonella typhi and Salmonella typhimuriurn. is presented. The infection was found to be superimposed upon pre-existing, obstructional damage due to nephrolithiasis or tuberculosis. In 3 patients, the infection had led to the development of a perinephric abscess, 11 to 14 years after the attack of typhoid fever. In all patients with unilateral kidney damage, only one kidney was found to be infected with Salmonella. Antibiotic treatment suppressed the excretion of bacteria only temporarily. N' ephrectomy or removal of the obstruction of urinary flow terminated the Salmonella carrier state m all patients with unilateral involvement. 8 Whitby, J.M. F.: Ampicillin in the treatment of Salmonella typhi carriers. Lancet, 2: 71, 1964.
TttE .JocRNAL oF UROLOGY
Copyright© l965 by The Williams & VVilkins Co.
SAL~\IONELLA INFECTIONS OF THE KIDNEY M. MELZER, G. ALT.MA.KN, M. RAKOWSZCYK, Z. H. YOSIPOYITCH
,IKD
B. BARSILAI
From the Departments of Urology ancl Bacteriology, Government Hospital Tei-Hashomer, Tel-Aviv ancl the Department of Urology, Hebrew University-Haclcrnsah Medical School, Jerusalem, Israel
The patient had been an inmate of a concentration camp in 1942. She contracted typhoid fever and became a carrier of the disease. For approximately 5 years prior to her admission she had recurrent episodes of urinary tract infection which usually responded to chloramphenicol. On admission in 1955 an abscess near the right iliac crest was detected and found to be connected to the right urinary tract. Sal. typhi was isolated from pus from the perinephric abscess as well as from the urine. X-rays of the chest and the spine demonstrated old, healed tuberculous processes of both lungs. The Dll vertebra had collapsed. An excretory urogram revealed the right kidney to be small and not excreting. Hydronephrosis and hydrometer were noted on the left side. Cystoscopy showed a contracted bladder. The ureteral orifices could not be identified. Cystography demonstrated bilateral reflux (fig. 1). Despite treatment with chloramphenicol and other antibiotics, the patient's condition slowly deteriorated. Urine cultures were consistently positive for Sal. typhi, except for periods when large doses of chloramphenicol were administered. Urine cultures for tuberculosis were twice negative. Death in May 1956 was due to shock. Postmortem examination disclosed caseous tuberculosis of the left kidney. The right kidney was completely destroyed by multiple abscesses which reached down to the fistula near the right iliac crest. Abscesses consisting of tuberculoid granulation tissue were found in the pancreas. Case 2. B. F., a 38-year-old wmnan, was admitted to the hospital in 1954 with fever, weakness and pains in the loin. Typhoid fever was suspected; the ·widal reaction test was positive, 1/100 for Sal. typhi O and H. The patient was treated with chloramphenicol. Blood sedimentation rate was 90/127 mm. Blood and urine cultures were sterile. The urine contained album.in and many leukocytes. An excretory urogram. revealed a normal right kidney. The left kidney showed some calcification and weak and delayed excretion. No pathological changes were seen
During an attack of typhoid fever the causative organisms are found during the acute stage of the disease in the bloodstream, bone marrow, spleen and biliary system. The kidneys are usually not involved, but statistics indicate that before the introduction of chloramphenicol for the treatment of typhoid fever, 20 to 40 per cent of patients excreted Salmonella in the urine, usually during the second or third week of the disease. As the passage of bacteria through the intact kidney is not probable, bacilluria in typhoid fever is explained by toxic nephrosis1 or by the formation of micro-abscesses or metastatic foci in the kidney. These lesions disappear during convalescence in the majority of patients. In persons with pre-existing pathological changes such as nephrolithiasis, 2 • 3 hydroncphrosis, anatomical anomaly or, especially in endemic areas like Egypt, urinary schistosomiasis, 4 • 5 the Salmonella organis1ns establish themselves in the damaged tissue and produce chronic infection. A perinephric abscess may develop if the bacteria penetrate into the perinephrium; or pyelonephritis results, bacteria are shed constantly in the urine and the patient becomes a urinary carrier. The epidemiological importance of permanent urinary excreters of Salrn.onella is well documented and need not to be elaborated further. As infections of the kidneys clue to Salmonella and their treatrn.ent are of interest to the clinician as well as to the epidemiologist, the case histories of the following 10 patients who came to our attention from. 1952 to 1959 are presented. CASE REPORTS
Primary damage: tuberculosis of kidney Case 1, P. K., a 63-year-old woman, was born in Romania and had lived for 6 years in IsraeL
Accepted for publication November 10, 1964. 1 Bumke, E.: Yirchow's Arch., 256: 446, 1925. 2 Patch, F. S.: Typhoid infection of the kidney. J. Urol., 14: 199, 1925. 3 Dreyfuss, F. and Hoth, J.: Typhoid bacilluria and urolithiasis. Amer. J. Med. Sci., 210: 591, 1945. 4 Neva, F. A.: Urinary enteric carriers in Egypt. Amer. J. Trop. Med., 29: 909, 1949.
5 Miller, W. S. and Floyd, T. M. Chronic urinary Salmonella carriers. Lancet, 1: 343, 1954.
23
24
MELZER AND ASSOCIATES
Fm. 1. Case 1. Cystography demonstrating bilateral reflux. in the bladder. Left retrograde pyelography demonstrated reflux connected to a cavity. Urine was collected for cultures and guinea pig inoculation. Triple-drug treatment was started. An excretory urogram, taken 3 months later, showed the left kidney to be displaced and the shadow of the psoas obscured (fig. 2). The patient was operated on and a perinephric abscess was found. The kidney was displaced laterally and downwards. Pus taken from the abscess grew Sal. typhi. Cultures and guinea pig inoculation from urine taken before operation were positive for Mycobacterium tuberculosis. A sinus developed at the site of the incision. Pus obtained from this sinus yielded Sal. typhi for 2 months. Urine and stool cultures were negative. The patient disclosed that 14 years ago she had had typhoid fever. Despite tripledrug treatment the tuberculous process in the kidney progressed as shown by an excretory urogram. A left nephrectomy was performed. Histological examination of the kidney showed tuberculoid reaction on the tip of the papillae and peripelvic tissue and acid-fast bacilli could be demonstrated. Recovery was uneventful. Urine cultures taken up to the year 1963 were negative both for Sal. typhi and Mb. tuberculosis.
Case 3. M. H. B., a 14-year old boy, born in Yemen, was adn1itted to the hospital in 1954 with fever, rigor and bloody urine. The liver and spleen were enlarged. The urine contained many erythrocytes and leukocytes. His parents told of numerous attacks of hematuria in the past. Cystolithotomy was probably performed when the boy was 6 years old. There was no history of typhoid fever. An excretory urogram revealed the left kidney to be completely calcified and non-functioning. Good excretion was present on the right side but many calculi were seen in the calyces (fig. 3). Urine cultures grew Sal. typhi. Repeated stool cultures were negative. The patient ·was treated with chloramphenicol, 1 gm. a day. The fever subsided and urine cultures became negative. Two months later he was re-admitted with similar complaints. Urine cultures were again positive for Sal. typhi. He was again treated with chlorarnphenicol and becarn.e afebrile. After his discharge from hospital the patient did not return for followup examinations. Three years later he underwent a left nephrectomy elsewhere. Histological examination of the kidney showed a tuberculous process. In 1960 a cold abscess on the side of the operation was incised and in 1961, incision and drainage of a periurethral abscess were accomplished. One urine culture in 1962 was negative; however, a urine specimen obtained a year later grew Sal. typhi. This patient continues to pass Salmonella in the urine, 10 years after his carrier state was first detected. Case 4. Ch. A., a 30-year-old man, born in
Fm. 2. Case 2. Excretory urogram shows lateral displacement of left kidney. Shadow of psoas obscured.
SALMONELLA INFECTIONS OF KIDNEY
I
'j I
Fw. 3. Case 3. Excretory urogram shows calcified left kidney. Calculi in calyces of right kidney.
I I
Yemen, was admitted to the hospital in 1956 with left renal colic and fever. His illness had started 4 months ago. On admission he was undernourishecl. ]'darked tenderness ,Yas noted on percussion of the left kidney. An excretory urogram showed a normally excreting right kidney. The pelvis and calyces of the left kidney were filled with calculi and excretion was markedly reduced. Left retrograde pyelography revealed an enlarged pelvis and obstruction of rn.ost calyces (fig. 4). Despite treatment with chloramphenicol and streptomycin, urine cultures repeatedly yielded Sal. typhimurium. Stool cultures were negative. The patient was readmitted with the same complaints a month later and again he was treated with antibiotics without success. Therefore, a left nephrectom.y was performed. Chloramphenicol was given as a prophylactic measure. Histological examination of the kidney showed caseous tuberculosis. Recovery was uneventful and the patient was put on triple antituberculous therapy. Repeated urine cultures postoperatively were negative.
25
tions were positive for Sal. typhi O and m a titer of 1 /100. An excretory urogram revealed an enlarged, calcified, non-excreting left kidney with calculi. The shadow of the psoas muscle was obscured by a mass reaching down to the iliac crest. The right kidney was normal. CystoRcopy revealed a normal bladder, but the left ureteral orifice could not be identified. At operation, a large abscess, enclosed by a fibrotic capsule, containing 1200 ml. pus, was found. The abscess connected with the lower pole of the left kidney. The abscess was drained, extirpated and nephrectomy was performed. Cultures of pus from. the abscess as well as that taken from the pelvis of the kidney grew Sal. typhi. Histological examination showed pyohyclronephrosis with stones and a bifid pelvis. The kidney parenchyma was destroyed and transform.eel to a thin fi brotic layer. Recovery was uneventful. Urine cultures were negative 3 years later. The patient told of having had typhoid fever 11 years ago. Case 6. D. A., a 24-year-old woman, born in Yemen, was admitted to the hospital in 1959 with urinary tract infection 4 years in duration. There was no history of typhoid fever. An excretory urogram disclosed a ptotic, excreting right kidney. Calculi were present in the left kidney and no excretion was visualized. Left retrograde pyelography disclosed that the kidney was obstructed by calculi. Urine cultures grew Sal. typhi. Stool cultures were negative. A urine specimen ob-
Primary damage: nephrolithiasis Case 5. Z. E., a 22-year-old woman, was admitted to the hospital in 1954 with fever, rigor and pains in the left upper abdomen, where a mass could be palpated. Urine specimens contained traces of album.in and some pus cells. Cultures grew Staphylococcus aureus and were negative for Salmonella and JVIb. tuberculosis. The leukocyte count was 15,000 and the blood sedimentation rate was 56 mm. the first hour. Serum agglutina-
Fm. 4. Case 4. Left retrograde pyelography demonstrates an enlarged pelvis with obstructed calyces.
26
MELZER AND ASSOCIATES
tained by ureteral catheter from the right (normal) kidney was sterile. Results of the Widal test were as follows: Sal. typhi, 0, positive 1/100; Sal. typhi, H, positive 1/400. No Vi agglutination was performed. A left nephrectomy was accomplished. Chloramphenicol was given as a prophylactic measure. Urine specimens taken during operation from the left pelvis again grew Sal. typhi. Pathological examination showed the kidney to be completely destroyed by pyelonephritis due to calculous obstruction. Urine cultures postoperatively were negative. In this patient it was possible to prove that the infection by Sal. typhi was localized in the diseased kidney. Case 7. B. R., a 33-year-old woman, born in Tripoli, was admitted to the hospital in 1955 with pains in the loins, fever and a blood urea of 90 mg. per cent. An excretory urogram showed a small calculus in the pelvis of the left kidney with good excretion. The right kidney showed a staghorn calculus and was non-excreting. There were no pathological changes in the bladder. Urine cultures were positive for Sal. typhi. Stool cultures were negative. Treatment with chloramphenicol, 1 gm. per day, was started and sulfadiazine ·and nitrofurantoin were given later. Urine cultures during treatment became negative. Serum agglutination was Sal. typhi, 0, negative 1/100; Sal. typhosa, H, positive, 1/400; and Vi, positive, 1/40. The patient was readmitted 2 months later. Her left ureter was found to be obstructed by the calculus which had descended from the pelvis to the mid-ureter. A left ureterolithotomy was performed. Recovery was uneventful and postoperative urine cultures were negative. A year later the patient was admitted for curettage. Sal. typhi was again cultured from the urine. Stool cultures were negative. This pointed to the right kidney as the source of Sal. typhi. Retrograde pyelography confirmed earlier findings and a right nephrectomy was performed. Histological examination of the kidney showed destruction due to calculi and chronic pyelonephritis. Urine cultures 2 years postoperatively were negative. Case 8. T. R., an 18-year-old boy, born in Tripoli, was first admitted to the hospital in 1955 with pains in the loins and hematuria. An excretory urogram demonstrated multiple calculi in the right upper calyx and on the left side, a
stricture of the ureteropelvic junction with hydronephrosis. Function was present in both kidneys. The patient left the hospital on his own request before the investigation could be completed. He was admitted to different hospitals for the same complaints during the next few years. In 1962 he was readmitted to our hospital with the same finding'S. Repeated urine cultures were positive for Sal. typhi. Stool cultures and cultures from duodenal contents were negative. Cholecystography was normal. Left pyeloplasty was performed. Urine cultures during the ensuing year after operation grew Pseudomonas aeruginosa and Escherichia coli, but were negative for Sal. typhi. As the patient is under continuous antibiotic treatment, it is too early to decide whether the Sal. typhi infection has responded to therapy. Case 9. S. B., a 28-year-old woman, was admitted in 1955 with pollakiuria, dysuria and pains in the loin of 1 year's duration. An excretory urogram showed right hydronephrosis due to a calculus in the pelvis and two small calculi in the calyces. The left kidney was normal. The urine contained many pus cells and repeated cultures grew Sal. typhi. Separate urine specimens obtained from the left and right kidney grew Sal. typhi from the right side only. Cultures from the left kidney were sterile. The patient said that she had had typhoid fever 12 years ago. She was treated with 15 gm. chloramphenicol for 10 days. Urine cultures taken after treatment were again positive. Right nephrotomy was performed and recovery was uneventful. She was seen in our outpatient department several times until 1962. All urine cultures were negative for Sal. typhi. Case 10. H. B., a 44-year-old woman, underwent a left pyelolithotomy in 1949. She was admitted to the hospital in 1952 with bilateral nephrolithiasis and hydronephrosis. The urine contained albumin and many leukocytes. Cultures grew Sal. typhi. She had had typhoid fever 10 years before. A right nephrolithotomy and partial nephrectomy were performed and multiple stones were removed. Histological examination of the removed tissue revealed chronic and acute pyelonephritis. It was possible to grow Sal. typhi from a calculus. Urine cultures after operation were again positive for Sal. typhi. The patient was again hospitalized 2 years later and a left nephrolithotorn.y was performed. Bilateral hydronephrosis is still present and the
27
SALMONELLA INFECTIONS OF KIDNEY
right kidney is apparently contracting. The patient is under continuous antibiotic treatment. Although cultures taken after the second operation were negative for Sal. typhi, it is not yet possible to state whether the infection finally responded to therapy. DISCUSSION
To the pre-existing diseases favoring infection of Sahnonella, tuberculosis of the kidney should be added, ,vhich was found (with or without nephrolithiasis) in four of our patients. This combination has been described only once 6 but should be looked for in every case of Salmonella infection of the urinary tract. All our patients had serious obstructive disease of the kidney. In three a perinephric abscess had developed from which Sal. typhi was isolated. In two of these, tuberculosis of the kidney was apparently the primary damage. The long interval (11 to 14 years) between the attack of typhoid fever and the first symptoms of the perinephric abscess is noteworthy. Perinephric abscess due to Salmonella is a rare entity and probably not more than four bacteriologically proved cases have been describecl.7 Salmonella reaches the kidneys by the hematogenous route and apparently both kidneys are originally infected. The infection persists on one side only, if the pathological changes are restricted to one kidney. That the infection was unilateral could be shown indirectly in 2 patients who ceased to excrete the causative organism in the urine after nephrectomy and in 2 patients with perinephric abscess. In 2 patients (cases 6 and 9) it was possible to prove that the infection was unilateral by examining urine samples from 6 Veelken, D.: Typhuspyonephrose in Kombination mit Nierentuberkulose und Nierenstcin. Zeit Urol., 5~: 721, 1961. 7 Yosipovitch, Z. H.· Typhoid perinephric abcess. Thesis: The Hebrew University Hadassah Medical School, Jerusalem, 1957.
the left and right kidney separately, On the other hand one patient (case 3) with bilateral kidney damage, on whom nephrectomy was perform.eel 3 years after Sal. typhi was first detected in the urine, continued to excrete bacteria intermittently and his last positive culture was obtained 7 years after operation. Long folluwup periods and repeated cultures are necessary till a carrier can be declared as cleared, if damage of the kidney still persists. Although all patients who excreted Salmonella were treated with chloramphenicol, tetracycline, streptomycin and nitrofurantoin for relatively long periods and ceased to excrete the organism during treatment, all yielded positive cultures again after antibiotics were cliscontinuecL Only surgical removal of the diseased kidney or the obstruction terminated the Sahnonella carrier state. Recent trials ·with ampicillin point to the possibility that certain carriers may be cleared with high doses and prolonged treatment with this new semi-synthetic penicillin. 8 SUMMARY
A report of 10 patients with chronic infection of the kidney due to Salmonella typhi and Salmonella typhimuriurn. is presented. The infection was found to be superimposed upon pre-existing, obstructional damage due to nephrolithiasis or tuberculosis. In 3 patients, the infection had led to the development of a perinephric abscess, 11 to 14 years after the attack of typhoid fever. In all patients with unilateral kidney damage, only one kidney was found to be infected with Salmonella. Antibiotic treatment suppressed the excretion of bacteria only temporarily. N' ephrectomy or removal of the obstruction of urinary flow terminated the Salmonella carrier state m all patients with unilateral involvement. 8 Whitby, J.M. F.: Ampicillin in the treatment of Salmonella typhi carriers. Lancet, 2: 71, 1964.