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Shigella alkalescens as a cause of pyelocystitis with bacteremia
Shigella
Alkalescens as a Cause of Pyelocystitis with Bacteremia GEORGE C. SUTTON,
M.D.
and ARTHUR BERNSTEIN,M.D.
Chicago, Illinois
T
Kenzie and Ratner.s This patient was a thirty-one year old woman with signs of right pyelitis. S. alkalescens was isolated from the urine, stool and blood. She was treated symptomatically and had a slow clinical response. No agglutination studies were made other than the Widal, which was negative. Starkey9 presented the case of a thirty-one year old woman who had a history of diarrhea and constipation a year previously. Acute pyelocystitis developed, with a pure culture of S. alkalescens in her urine and blood only. No agglutination reaction developed throughout the illness. However, the systemic reaction was demonstrated by precipitin and complement fixation tests. Slow improvement was achieved by treatment with urotropin. In 1948 Car-don and Felsenfeldlg published a case report of a twenty-two year old nurse with dysentery and pyelocystitis. S. alkalescens was identified in the blood and urine. The serum of the patient agglutinated the S. alkalescens strain isolated from the patient in a dilution of 1:320. Recovery was made rapid by treatment with sulfadiazine, and the organism was inhibited by 2 mg. per 100 cc. sulfadiazine in vitro. To these cases of S. alkalescens pyelocystitis with bacteremia is added one observed at the Cook County Hospital.
HE organism now known as Shigella alkalescens was first isolated by Andrewes’ in 1918. He recovered the bacillus from the stools of patients convalescent from dysentery and did not consider it to be pathogenic for human beings. It was classified as an atypical dysentery bacillus resembling the Flexner type and was named because it gave a characteristic, strongly alkaline reaction in litmus milk. He observed “No case has been met with in which it (Shigella alkalescens) has been agglutinated by the serum of the patient from whom it has been isolated.” Since Foerster’s observation in 19182 of pyelitis caused by the Flexner bacillus it has become recognized that shigella of both the Flexner and Hiss-Russel Y type are rather frequent causes of pyelocystitis.3 However, proof that S. alkalescens is truly pathogenic for human beings has been only recently established.4 A review of the literature to date reveals but twenty-three reported instances of recovery of S. alkalescens from the urine of individuals with clinical signs of pyelocystitis. (Table I.) In only four of these cases has S. alkalescens been recovered from both the urine and blood. In 1928 Smith and Fraser’ reported the first occurrence of S. alkalescens bacteremia in a woman four days after an uncomplicated delivery; blood, urine, feces and uterine swabs all contained the organism. Her clinical course was chronic and she remained febrile for a month under nonIn the patient’s serum specific therapy. agglutinins for the blood strain developed in a dilution of 1 : 120 and for the urinary strain in a dilution of 1 :480. The second case was reported by Mac-
CASE REPORT A nineteen year old married colored woman, a power machine operator, was admitted to the hospital on March 17, 1948, with a history of an aching pain in her right back for four days. The pain had increased in intensity and was accompanied with moderately increased fre422
AMERICAN
JOURNAL
OF
MEDICINE
S. Alkalescens
Infections--Sutton,
quency of urination. She vomited once and felt feverish twenty-four hours before admission. Physical examination revealed a well nourished young Negro woman who was toxic with a fever of 104”F., pulse, 120, regular rhythm and a respiratory rate, 28. Physical signs were
-
Irganism Year
Serum Agglutination Stool
Urine
-
-
Treatment
and Response
--
Smith and Fraser6
F
+
+
+
1929 1931
Weil, A. J.” Popoff and Spanswick?
F F
-
+ +
_
+
F
+
+
+
and Ratnerf 3
Etet
: I3lood
1928
1’134 MacKenzie
I
Present In
I!Se3: -
Authors
423
diagnosis of acute right pyelitis with cystitis was made and the patient was given sulfadiazine, 4 gm. initially and 1 gm. every four hours. Eight hours later her white blood cell count was 12,150 with 80 per cent polymorphonuclear cells, her red cell count 4,OOO.OOOand hemoglobin of 68
TABLE
--
Bernstein
n
Blood strain Urine strain Not stated 1:640
1 : 120 1 : 480
Not stated Not stated Therapeutic abortion with good response Symptomatic, poor response Urotropin. poor response
1934
Starkeys
F
0
+
+
1934 1936
Murray and Piker0 Snyder, M. and Hanner, J.” Neter, E.t2 Case 1 Case 2
-
0
+
0
Negative Widal No agglutinins Positive precipitin and complement fixation tests 1:640 Not stated
F F F
+ 0 0
+ + +
0 0 0
No agglutinins No agglutinins 1:500
Neter and Rappole’s Case 1
F
0
+
0
Case 2
F
0
+
0
Case 3 Wooley, P. V. and Sweet M.r4 Case 1 Case 2 Case 3 Case 4
F
0
+
0
to Agglutinins titer Agglutinins to titer No agglutinins
F F F F
+
+
i 0
: +
0 0 0 0
Not stated Not stated 1:1280 No agglutinins
Ketogenic diet. responded Methenamine, responded Symptomatic, responded Methenamine and NH&I, slow response
-
+
+
0
No agglutinins
Not stated
_ -
:
c 0
Not stated Not stated
Not stated Not stated
F
0
1 +
+
1:320
Sulfadiazine, rapid response
1938
1938
1938
1938 1943 1943 1948
Nabarro, D. and Edward, D.t5 Welch and Mickle16 4 cases Roux, P.r’ Cardon, I,. and Felsenfeld, O.rs
’
Urotropin, poor response Prontylin, rapid response Mandelic acid, good response unstated
Not stated
unstated
Not stated Not stated
--
entirely negative except for definite tenderness on. palpation over the right kidney area. There was marked pain on percussion over the right costovertebral angle. A white, creamy, cervical discharge was noted and a Gram’s stain of it showed many extracellular gram-negative cocci. Admission urinalysis revealed many clumped white blood cells and a positive test for albumin. Urine and hlood culture taken at that time produced a pure culture of S. alkalescens. A SEPTEMBER.
1950
per cent. The non-protein nitrogen was 32 mg. per cent, the total protein 7.4 gm. per cent and the Kahn test was negative. A flat plate of the abdomen revealed no pathologic disorder. The fever dropped rapidly and on the fifth day of therapy (March 22, 1948) the patient became afebrile and well and has remained so. On the seventh hospital day both urine and hlood cultures were sterile. The stool cultures contained no enteric pathogens. Four suhse-
424
S. Alkalescens
Infections-Sutton,
quent stool, urine and blood cultures showed similar results. Tests of the patient’s serum were carried out as follows: There was no agglutination with typhoid “H” and “0,” paratyphoid “A” and “B” and Brucella antigens. However, on the fifteenth day of illness (March 28, 1948) the serum agglutinated the organism isolated from the patient’s urine to a dilution of 1: 1,280. On the twenty-fifth day of illness (April 7th) the agglutination titer for that organism was 1 : 640. By the thirty-ninth day of illness (April 21st) the serum agglutinated the urinary strain in a dilution of only 1 :320; there was no agglutination of the organism isolated from the blood.
COMMENTS
The study of this case lends additional evidence that S. alkalescens is pathogenic for human beings. Review of the literature reveals that it is occasionally the cause of pyelocystitis and rarely the cause of bacteremia. Development of serum agglutinins of high titer during the acute phase of this case and their subsequent rapid decline is further evidence of the pathogenicity of this organism. In one other case9 in which serum agglutinins were not demonstrable, precipitins and complement fixation reactions were detected. It is worth while to note that Neter12 in 1938 described a rapid recovery with the use of prontylin. A drug of the sulfonamide group was not used again until 1948 by Cardon and Felsenfeld.‘s All other cases were treated either symptomatically or with the commonly used urinary tract medications. Although no mortality has been reported, the morbidity has been decreased by the use of sulfonamides.
SUMMARY 1. All reported cases of urinary tract infection due to Shigella alkalescens have been summarized. Four cases of pyelocystitis with bacteremia have been analysed and an additional case reported. 4. There is a prompt therapeutic response
Bernstein
administration mide group. to
of drugs of the sulfona-
Acknowledgment: We are indebted to Dr. Oscar Felsenfeld, M.D., head of the Department of Bacteriology, Cook County Hospital, for the bacteriologic and serologic studies. REFERENCES
1. ANDREWES, F. W. Dysentery bacilli: the differentiation of the true dysentery bacilli from allied species. Lancet, 194: 560, 1918. 2. FOERSTER, A. Ein Fall von Zystopyelitis hervorgerufen durch Ruhr Bazillen (Typus Flexner). Miinchen. med. Wchnschr., 65: 205, 1918. 3. HILCERS, E. W. Pseudodysenteriebazillen als Erreger von Cystopyelitis. Centralbl. f. Bakt., 83: 414, 1919. CHEATHAM,G. R. Pyelonephritis of pregnancy due to bacillus dysenteriae. Am. .7. Obst. d Gynec., 28: < 448,1934. 4. NABARRO,D. and EDWARD, D. The pathogenicity of bacterium alkalescens. .-I. Path. & Bact.. 49: 515528, 1939. 5. SMITH, J. and FRASER, A. M. A case of continued fever due to bacillus alkalescens Andrewes. J. Path. & But., 31: 511, 1928. 6. WEIL, A. J. Ueber den Bacillus alkalescens. Centralbl. f. Bakt., 112: 376-378, 1929. 7. POPOPF, N. W. and SPANSWICK: M. P. A case of pyelonephritis of pregnancy due to eberthella alkalescens. 3. Lab. & Clin. Med., 16: 437, 1931. 8. MACKENZIE, D. W. and RATNER, M. Bacillus alkalescens pyelonephritis with blood infection. 3. Ural.,31: 671, 1934. 9. STARKEY, D. H. A case of bacillus alkalescens (Andrewes) bacteremia with serological confirmation. Canod. M. A. 7.. 31: 41. 1934. 10. MURRAY, M. F. and PIKE, R. M. Acute pyelitis due to Shigella alkalescens. Clin. Misc. Mary I. Bassett Ho@., 1: 68-71, 1934.14 11. SNYDER, M. and HANNER, J. Bacilluria caused by B. alkalescens. 3. Infect. Dis., 60: 51, 1936. 12. NETER, E. Infections of the urinary tract due to Shigella paradysenteriae and allied species. 3. But., 35: 202, 1938. 13. NETER,. E. ~~~.RAPPOLE. Pathogenicity and antigenie structure of Shigella alkalescens. Arch. Path., 25: 298, 1938. 14. WOOLEY, P. V. and SWEET, M. The significance of Shigella alkalescens. 3. Pediat., 12: 596-602, 1938. 15. NABARRO, D. and EDWARD, D. The pathogenicity of bacterium alkalescens. 3. Path. @ Bact., 49: 515-528, 1939 16. WELCH, H. and MICKLE, F. L. Relationship of Shigella alkalescens Shigella group. Am.
to
other
members
of
the
3. Pub. Health, 24: 219-228,
1943. 17. Roux, P. Intestinal and urinary infections of Bacillus alkalescens. South African M. J., 17: 6, 1943. 18. CARDON, L. and FELSENFELD,0. A case of Shigella alkalescens cystopyelitis and bacteremia. Am. 3. Clin. Path., 18: 55-57, 1948. AMERICAN
JOURNAL
OP MEDICINE
Alkalescens as a Cause of Pyelocystitis with Bacteremia GEORGE C. SUTTON,
M.D.
and ARTHUR BERNSTEIN,M.D.
Chicago, Illinois
T
Kenzie and Ratner.s This patient was a thirty-one year old woman with signs of right pyelitis. S. alkalescens was isolated from the urine, stool and blood. She was treated symptomatically and had a slow clinical response. No agglutination studies were made other than the Widal, which was negative. Starkey9 presented the case of a thirty-one year old woman who had a history of diarrhea and constipation a year previously. Acute pyelocystitis developed, with a pure culture of S. alkalescens in her urine and blood only. No agglutination reaction developed throughout the illness. However, the systemic reaction was demonstrated by precipitin and complement fixation tests. Slow improvement was achieved by treatment with urotropin. In 1948 Car-don and Felsenfeldlg published a case report of a twenty-two year old nurse with dysentery and pyelocystitis. S. alkalescens was identified in the blood and urine. The serum of the patient agglutinated the S. alkalescens strain isolated from the patient in a dilution of 1:320. Recovery was made rapid by treatment with sulfadiazine, and the organism was inhibited by 2 mg. per 100 cc. sulfadiazine in vitro. To these cases of S. alkalescens pyelocystitis with bacteremia is added one observed at the Cook County Hospital.
HE organism now known as Shigella alkalescens was first isolated by Andrewes’ in 1918. He recovered the bacillus from the stools of patients convalescent from dysentery and did not consider it to be pathogenic for human beings. It was classified as an atypical dysentery bacillus resembling the Flexner type and was named because it gave a characteristic, strongly alkaline reaction in litmus milk. He observed “No case has been met with in which it (Shigella alkalescens) has been agglutinated by the serum of the patient from whom it has been isolated.” Since Foerster’s observation in 19182 of pyelitis caused by the Flexner bacillus it has become recognized that shigella of both the Flexner and Hiss-Russel Y type are rather frequent causes of pyelocystitis.3 However, proof that S. alkalescens is truly pathogenic for human beings has been only recently established.4 A review of the literature to date reveals but twenty-three reported instances of recovery of S. alkalescens from the urine of individuals with clinical signs of pyelocystitis. (Table I.) In only four of these cases has S. alkalescens been recovered from both the urine and blood. In 1928 Smith and Fraser’ reported the first occurrence of S. alkalescens bacteremia in a woman four days after an uncomplicated delivery; blood, urine, feces and uterine swabs all contained the organism. Her clinical course was chronic and she remained febrile for a month under nonIn the patient’s serum specific therapy. agglutinins for the blood strain developed in a dilution of 1 : 120 and for the urinary strain in a dilution of 1 :480. The second case was reported by Mac-
CASE REPORT A nineteen year old married colored woman, a power machine operator, was admitted to the hospital on March 17, 1948, with a history of an aching pain in her right back for four days. The pain had increased in intensity and was accompanied with moderately increased fre422
AMERICAN
JOURNAL
OF
MEDICINE
S. Alkalescens
Infections--Sutton,
quency of urination. She vomited once and felt feverish twenty-four hours before admission. Physical examination revealed a well nourished young Negro woman who was toxic with a fever of 104”F., pulse, 120, regular rhythm and a respiratory rate, 28. Physical signs were
-
Irganism Year
Serum Agglutination Stool
Urine
-
-
Treatment
and Response
--
Smith and Fraser6
F
+
+
+
1929 1931
Weil, A. J.” Popoff and Spanswick?
F F
-
+ +
_
+
F
+
+
+
and Ratnerf 3
Etet
: I3lood
1928
1’134 MacKenzie
I
Present In
I!Se3: -
Authors
423
diagnosis of acute right pyelitis with cystitis was made and the patient was given sulfadiazine, 4 gm. initially and 1 gm. every four hours. Eight hours later her white blood cell count was 12,150 with 80 per cent polymorphonuclear cells, her red cell count 4,OOO.OOOand hemoglobin of 68
TABLE
--
Bernstein
n
Blood strain Urine strain Not stated 1:640
1 : 120 1 : 480
Not stated Not stated Therapeutic abortion with good response Symptomatic, poor response Urotropin. poor response
1934
Starkeys
F
0
+
+
1934 1936
Murray and Piker0 Snyder, M. and Hanner, J.” Neter, E.t2 Case 1 Case 2
-
0
+
0
Negative Widal No agglutinins Positive precipitin and complement fixation tests 1:640 Not stated
F F F
+ 0 0
+ + +
0 0 0
No agglutinins No agglutinins 1:500
Neter and Rappole’s Case 1
F
0
+
0
Case 2
F
0
+
0
Case 3 Wooley, P. V. and Sweet M.r4 Case 1 Case 2 Case 3 Case 4
F
0
+
0
to Agglutinins titer Agglutinins to titer No agglutinins
F F F F
+
+
i 0
: +
0 0 0 0
Not stated Not stated 1:1280 No agglutinins
Ketogenic diet. responded Methenamine, responded Symptomatic, responded Methenamine and NH&I, slow response
-
+
+
0
No agglutinins
Not stated
_ -
:
c 0
Not stated Not stated
Not stated Not stated
F
0
1 +
+
1:320
Sulfadiazine, rapid response
1938
1938
1938
1938 1943 1943 1948
Nabarro, D. and Edward, D.t5 Welch and Mickle16 4 cases Roux, P.r’ Cardon, I,. and Felsenfeld, O.rs
’
Urotropin, poor response Prontylin, rapid response Mandelic acid, good response unstated
Not stated
unstated
Not stated Not stated
--
entirely negative except for definite tenderness on. palpation over the right kidney area. There was marked pain on percussion over the right costovertebral angle. A white, creamy, cervical discharge was noted and a Gram’s stain of it showed many extracellular gram-negative cocci. Admission urinalysis revealed many clumped white blood cells and a positive test for albumin. Urine and hlood culture taken at that time produced a pure culture of S. alkalescens. A SEPTEMBER.
1950
per cent. The non-protein nitrogen was 32 mg. per cent, the total protein 7.4 gm. per cent and the Kahn test was negative. A flat plate of the abdomen revealed no pathologic disorder. The fever dropped rapidly and on the fifth day of therapy (March 22, 1948) the patient became afebrile and well and has remained so. On the seventh hospital day both urine and hlood cultures were sterile. The stool cultures contained no enteric pathogens. Four suhse-
424
S. Alkalescens
Infections-Sutton,
quent stool, urine and blood cultures showed similar results. Tests of the patient’s serum were carried out as follows: There was no agglutination with typhoid “H” and “0,” paratyphoid “A” and “B” and Brucella antigens. However, on the fifteenth day of illness (March 28, 1948) the serum agglutinated the organism isolated from the patient’s urine to a dilution of 1: 1,280. On the twenty-fifth day of illness (April 7th) the agglutination titer for that organism was 1 : 640. By the thirty-ninth day of illness (April 21st) the serum agglutinated the urinary strain in a dilution of only 1 :320; there was no agglutination of the organism isolated from the blood.
COMMENTS
The study of this case lends additional evidence that S. alkalescens is pathogenic for human beings. Review of the literature reveals that it is occasionally the cause of pyelocystitis and rarely the cause of bacteremia. Development of serum agglutinins of high titer during the acute phase of this case and their subsequent rapid decline is further evidence of the pathogenicity of this organism. In one other case9 in which serum agglutinins were not demonstrable, precipitins and complement fixation reactions were detected. It is worth while to note that Neter12 in 1938 described a rapid recovery with the use of prontylin. A drug of the sulfonamide group was not used again until 1948 by Cardon and Felsenfeld.‘s All other cases were treated either symptomatically or with the commonly used urinary tract medications. Although no mortality has been reported, the morbidity has been decreased by the use of sulfonamides.
SUMMARY 1. All reported cases of urinary tract infection due to Shigella alkalescens have been summarized. Four cases of pyelocystitis with bacteremia have been analysed and an additional case reported. 4. There is a prompt therapeutic response
Bernstein
administration mide group. to
of drugs of the sulfona-
Acknowledgment: We are indebted to Dr. Oscar Felsenfeld, M.D., head of the Department of Bacteriology, Cook County Hospital, for the bacteriologic and serologic studies. REFERENCES
1. ANDREWES, F. W. Dysentery bacilli: the differentiation of the true dysentery bacilli from allied species. Lancet, 194: 560, 1918. 2. FOERSTER, A. Ein Fall von Zystopyelitis hervorgerufen durch Ruhr Bazillen (Typus Flexner). Miinchen. med. Wchnschr., 65: 205, 1918. 3. HILCERS, E. W. Pseudodysenteriebazillen als Erreger von Cystopyelitis. Centralbl. f. Bakt., 83: 414, 1919. CHEATHAM,G. R. Pyelonephritis of pregnancy due to bacillus dysenteriae. Am. .7. Obst. d Gynec., 28: < 448,1934. 4. NABARRO,D. and EDWARD, D. The pathogenicity of bacterium alkalescens. .-I. Path. & Bact.. 49: 515528, 1939. 5. SMITH, J. and FRASER, A. M. A case of continued fever due to bacillus alkalescens Andrewes. J. Path. & But., 31: 511, 1928. 6. WEIL, A. J. Ueber den Bacillus alkalescens. Centralbl. f. Bakt., 112: 376-378, 1929. 7. POPOPF, N. W. and SPANSWICK: M. P. A case of pyelonephritis of pregnancy due to eberthella alkalescens. 3. Lab. & Clin. Med., 16: 437, 1931. 8. MACKENZIE, D. W. and RATNER, M. Bacillus alkalescens pyelonephritis with blood infection. 3. Ural.,31: 671, 1934. 9. STARKEY, D. H. A case of bacillus alkalescens (Andrewes) bacteremia with serological confirmation. Canod. M. A. 7.. 31: 41. 1934. 10. MURRAY, M. F. and PIKE, R. M. Acute pyelitis due to Shigella alkalescens. Clin. Misc. Mary I. Bassett Ho@., 1: 68-71, 1934.14 11. SNYDER, M. and HANNER, J. Bacilluria caused by B. alkalescens. 3. Infect. Dis., 60: 51, 1936. 12. NETER, E. Infections of the urinary tract due to Shigella paradysenteriae and allied species. 3. But., 35: 202, 1938. 13. NETER,. E. ~~~.RAPPOLE. Pathogenicity and antigenie structure of Shigella alkalescens. Arch. Path., 25: 298, 1938. 14. WOOLEY, P. V. and SWEET, M. The significance of Shigella alkalescens. 3. Pediat., 12: 596-602, 1938. 15. NABARRO, D. and EDWARD, D. The pathogenicity of bacterium alkalescens. 3. Path. @ Bact., 49: 515-528, 1939 16. WELCH, H. and MICKLE, F. L. Relationship of Shigella alkalescens Shigella group. Am.
to
other
members
of
the
3. Pub. Health, 24: 219-228,
1943. 17. Roux, P. Intestinal and urinary infections of Bacillus alkalescens. South African M. J., 17: 6, 1943. 18. CARDON, L. and FELSENFELD,0. A case of Shigella alkalescens cystopyelitis and bacteremia. Am. 3. Clin. Path., 18: 55-57, 1948. AMERICAN
JOURNAL
OP MEDICINE