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Clostridium perfringens emphysematous cystitis
CLOSTRIDIUM PERFRINGENS EMPHYSEMATOUS CYSTITIS DOUGLAS S. KATZ, M.D. EROL AKSOY, M.D. BURKE A. CUNHA, M.D.
From the Infectious Disease Division, Department of Medicine, Winthrop-University Hospital, Mineola, and the School of Medicine, State University of New York, Stony Brook, New York ABSTRACT-Emphysematous cystitis is a rare disease and is usually caused by aerobic bacteria, most commonly Escherichia coli. Only rarely have anaerobic bacteria been associated with this condition. We report a case of emphysematous cystitis due to Clostridium perfringens with bacteremia in an elderly diabetic woman.
Emphysematous cystitis is a rare disease and is usually caused by aerobic bacteria, most commonly Escherichia coli. Only rarely have anaerobic bacteria been associated with this condition. We report a case of emphysematous cystitis due to Clostridium perfringens with bacteremia in an elderly diabetic woman. Case Report A seventy-five-year-old woman with a long history of noninsulin-dependent diabetes mellitus was transferred from her nursing home to Winthrop-University Hospital because of decreased responsiveness. She took glyburide for her diabetes, and she had a past medical history of transient ischemic attacks. Physical examination on admission revealed her to be a well-developed woman, alert and oriented to person, place, and time, but unable to give a clear history. Her rectal temperature was 36.9”C, pulse 76/minute, and blood pressure 120/80 mm Hg without orthostatic changes. There were no skin lesions, but bilateral arcus senilis was present. Fundi did not show diabetic retinopathy. Examination of the head, ears, nose, and throat were unremarkable. There were no carotid bruits. Her lungs were clear, and findings on cardiac and breast examinations were normal. Her abdomen was distended with a round palpable hypogastric
458
mass. The neurologic examination showed no focal deficits. Laboratory tests on admission were remarkable for a white blood cell count of 24.8 x K3/ mm3 with 88 % neutrophils and 4 % bands, and a hemoglobin of 10.2 g/dL. The blood urea nitrogen was 82 mg/dL and serum creatinine 2.5 mg/dL. The serum glucose was 77 mg/dL. The urine had more than 25 red and white blood cells per high-power field. A chest radiograph showed a tortuous and calcified aorta, and the electrocardiogram was normal. X-ray films of the abdomen with the patient in flat and upright positions showed a markedly enlarged bladder (16 cm in diameter) with gas outlining the circumference of the wall and filling the lumen (Fig. 1). During the day of admission, the patient’s temperature rose to 38.7 “C, and her serum glucose increased to 211 mg/dL. Ampicillin (1 g q4h) was started. On hospital day 2, the hypogastrium increased in prominence and placement of a Foley catheter with pressure over the bladder released a large amount of air. Blood cultures drawn that day were positive for C. perfringens at forty-eight hours, and aerobic urine cultures were negative. Treatment was changed to intravenous penicillin G, 6.7 units q4h, on hospital day 4. A cystogram several days later showed trabeculated bladder without evidence of vesicocolic or vesicovaginal
UROLOGY
I
MAY 1993 / VOLUME
41, NUMBER 5
FIGURE1. Plain film of abdomen shows markedly distended gas-filled bladder. Thin line of gas shown within bladder wall throughout its circumference.
fistula. Renal and pelvic sonogram findings were normal. The patient became afebrile on hospital day 10; her mentation improved, the serum glucose fell to 125 mg/dL, and blood urea nitrogen, serum creatinine, and white blood cell count all returned to normal levels. The stool became positive for occult blood, and colonoscopy showed hemorrhoids but no evidence of a fistula to the bladder. Comment Emphysematous cystitis is caused by gasforming organisms in the bladder. Gas, particularly carbon dioxide, may be formed in either the bladder wall or lumen, or in both locations. To date, 165 cases have been reported in the literature.‘-lg Gas may also enter the bladder from a fistula, from penetrating trauma, or following surgery or bladder instrumentation. l In 1961, Bailey2 noted that predisposing factors in 71 cases of emphysematous cystitis included glycosuria, particularly diabetes, lower urinary tract obstruction/urinary retention. There was often a history of chronic urinary
UROLOGY
/ MAY 1993
/ VOLUME
41, NUMBER5
tract infectionB3 The incidence in women was approximately twice that in men. Holesh4 reviewed 118 cases in 1969. Most of the patients were elderly, 58 were diabetics, and the average duration of their diabetes was fourteen years. Diabetes may be well controlled when emphysematous cystitis presents.5 Patients with emphysematous cystitis complain of frequency, urgency, nocturia, dysuria, or occasionally, pneumaturia. Urinalysis usually shows pyuria and hematuria in addition to glycosuria/ketonuria, suprapubic tenderness, and if the bladder is enlarged, it is usually palpable. 2.4,6 E. coli is the most common organism from the urine in emphysematous cystitis; less frequently, Enterobacter aerogenes, Staphylococcus aureus, streptococci, Klebsiella pneumoniae, Proteus mirabilis, Nocardia, or Candida albicans have been isolated from the urine.2.7-g While computerized tomography (CT) is a sensitive means of detecting gas in the bladder, a plain abdominal radiograph may be diagnostic.‘O A thin radiolucent line of streaks or gas bubbles may outline the bladder wall. These bubbles may have a “cobblestone” appearance when seen “en face.“2 The bladder wall may thicken and the gas coalesce into blebs or spheres, forming a “beaded necklace.“2,eJ1 Air also may be seen in the bladder lumen, with an air-fluid level on films with patient in erect position. Intravenous urography or retrograde cystography shows filling defects in the bladder if gas is present in its walls.g Within several days the gas usually disappears from radiographs.2 Cystoscopy is also diagnostic. Burns12 described finding numerous tiny gas bubbles embedded in a shaggy reddened bladder wall. Others have noted that these bubbles ruptured easily and gave off an exaggerated or silvery light reflex.6x11 C. perfringens is ubiquitous in soil and in the human intestinal tract. It causes soft tissue, intra-abdominal, and female genital tract infections, food poisoning, enteritis necroticans, and pulmonary infections. It is usually only one component of the flora in a polymicrobial infection. Gas formation occurs in only a minority of cases.13 Clostridium or other anaerobes rarely cause urinary tract infections. Anaerobes may be found at the urethral meatus and a positive anaerobic culture’s significance is not always clear.14.15 Headington and Beyerlein16 reported that only 158 anaerobes grew from 15,250
459
clean-catch midstream or catheterized urine specimens, including 57 species of Clostridia. Only 7 patients had symptoms of urinary tract infection and anaerobic isolates on pure culture (including two isolates of C. perfringens) . In no case could the infections be attributed to the anaerobes alone. Gorbach and Thadepalli” reviewed a series of 114 isolates of Clostridia. Other than a prostatic abscess, none involved the urinary tract. Nielsen and LaurserP reported a case of C. perfringens cystitis, without emphysematous changes, in an elderly diabetic woman. Our case is one of several in the literature associating C. perfringens with emphysematous cystitis. Levi+ described the first case in 1938, a fifty-seven-year-old woman with poorly controlled diabetes. The diagnosis was confirmed by cystoscopy and a positive urine culture. BurnsI reported the second case, a seventytwo-year-old woman without a diabetic history; however, E. coli and fi-hemolytic streptococci as well as C. perfringens grew from the urine. Wayland and Kiviat7 reported 2 cases with C. perfringens bacteremia, an eightyyear-old man and a sixty-two-year-old woman, both diabetics. Anaerobic urine cultures were not done in either case, but aerobic urine cultures were negative. Maliwan15 reported on a thirty-eight-year-old woman without diabetes with positive blood cultures. Again, anaerobic urine cultures were not obtained. Finally, West, Holley, and Lauer14 reported on a seventy-twoyear-old woman with well-controlled diabetes, with a positive urine culture. No urine Gram stain or anaerobic urine cultures were obtained from our patient. However, no explanation for emphysematous cystitis other than C. perfringens is plausible in view of negative aerobic urine cultures and C. perfringens bacteremia. Three of the previous cases also had positive blood cultures and negative aerobic urine cultures, and anaerobic urine cultures were not performed. Though it may be difficult to clearly associate positive clostridial blood cultures with concurrent infectious processes, gas production in this case links Clostridia to the cystitis. The pathogenesis of emphysematous cystitis in this case and in general is not clear. Sugar in
460
the urine may provide a reducing environment for anaerobic growth. The neurogenic bladder common in diabetics contributes to bladder distention and urinary retention; a distended bladder may have decreased ~0, in the urothelium, which may promote the growth of anaerobes. C. perfringens, as opposed to other clostridial species, can tolerate a low p02 of up to 90 mm
Hg*
Treatment of emphysematous cystitis includes control of diabetes, relief of urinary obstruction, and use of appropriate antibiotics. Infectious Disease Division Winthrop-University Hospital Mineola, New York 11501 (DR. CUNHA) References 1. Elkin M: Radiology of the urinary system, Boston, Little Brown & Co., ~012, 1980, pp 209, 217-221, 262-267. 2. Bailey H: Cystitis emphysematosa, AJR 86: 850 (1961). 3. LeDec A, Cariou G, and Jeaneau PL: Case profiles: cystitis emphysematosa, Urology 25: 88 (1985). 4. Holesh S: Gas in the bladder-cystitis emphysematosa, Clin Radio1 20: 234 (1969). 5. Vasumoto R, Asakawa M, and Nishisaka N: Emphysematous cystitis, Br J Uro163: 644 (1988). 6. Hawtrey CE, Williams JJ, and Schmidt JD: Cystitis emphysematosa, Urology 4: 612 (1974). 7. Wayland JS, and Kiviat MD: Clostridial cystitis emphysematosa, Urology 4: 601 (1974). 8. Bartkowski DP, and Lane&y JR: Emphysematous prostatitis and cystitis secondary to Candida albicans, J Urol 139: 1063 (1988). 9. Singh CR, and Lytle WF Jr: Cystitis emphysematosa caused by Candida albicans, J Urol 130: 1171 (1983). 10. Bohlman ME, Fishman EK, Oesterling JE, and Goldman SM: CT findings in emphysematous cystitis, Urology 32: 63 (1988). 11. Ellenbogen EH, and Talner LB: Uroradiology of diabetes mellitus, Urology 4: 413 (1974). 12. Burns RA: Cystitis emphysematosa, a case report, J Urol 49: 808 (1943). 13. Bartlett JG: Gas gangrene (other Clostridium-associated diseases), in Mandell GL, Douglas RG Jr, and Bennett JE (Eds): Principles and Practice of Infectious Diseases, New York, Churchill Livingstone, 1990, pp 1850-1858. 14. West TE, Holley HP Jr, and Lauer AD: Emphysematous cystitis due to clostridium perfringens, JAMA 246: 363 (1981). 15. Maliwan N: Emphysematous cystitis associated with Clostridium perfringens bacteremia, J Urol 121: 819 (1979). 16. Headington JT, and Beyerlein B: Anaerobic bacteria in routine urine culture, J Clin Path01 19: 573 (1966). 17. Gorbach SL, and Thadepahi H: Isolation of Clostridium in human infections: evaluation of 114 cases, J Infect Dis 131: S81 (1975). 18. Nielsen ML, and Laursen H: Clostridial infection in the urinary tract, Stand J Urol Nephro16: 120 (1972). 19. Levin HA: Gas cysts of urinary bladder, J Urol 39: 45 (1938).
UROLOGY
I
MAY 1993
I
VOLUME41,
NUMBER5
From the Infectious Disease Division, Department of Medicine, Winthrop-University Hospital, Mineola, and the School of Medicine, State University of New York, Stony Brook, New York ABSTRACT-Emphysematous cystitis is a rare disease and is usually caused by aerobic bacteria, most commonly Escherichia coli. Only rarely have anaerobic bacteria been associated with this condition. We report a case of emphysematous cystitis due to Clostridium perfringens with bacteremia in an elderly diabetic woman.
Emphysematous cystitis is a rare disease and is usually caused by aerobic bacteria, most commonly Escherichia coli. Only rarely have anaerobic bacteria been associated with this condition. We report a case of emphysematous cystitis due to Clostridium perfringens with bacteremia in an elderly diabetic woman. Case Report A seventy-five-year-old woman with a long history of noninsulin-dependent diabetes mellitus was transferred from her nursing home to Winthrop-University Hospital because of decreased responsiveness. She took glyburide for her diabetes, and she had a past medical history of transient ischemic attacks. Physical examination on admission revealed her to be a well-developed woman, alert and oriented to person, place, and time, but unable to give a clear history. Her rectal temperature was 36.9”C, pulse 76/minute, and blood pressure 120/80 mm Hg without orthostatic changes. There were no skin lesions, but bilateral arcus senilis was present. Fundi did not show diabetic retinopathy. Examination of the head, ears, nose, and throat were unremarkable. There were no carotid bruits. Her lungs were clear, and findings on cardiac and breast examinations were normal. Her abdomen was distended with a round palpable hypogastric
458
mass. The neurologic examination showed no focal deficits. Laboratory tests on admission were remarkable for a white blood cell count of 24.8 x K3/ mm3 with 88 % neutrophils and 4 % bands, and a hemoglobin of 10.2 g/dL. The blood urea nitrogen was 82 mg/dL and serum creatinine 2.5 mg/dL. The serum glucose was 77 mg/dL. The urine had more than 25 red and white blood cells per high-power field. A chest radiograph showed a tortuous and calcified aorta, and the electrocardiogram was normal. X-ray films of the abdomen with the patient in flat and upright positions showed a markedly enlarged bladder (16 cm in diameter) with gas outlining the circumference of the wall and filling the lumen (Fig. 1). During the day of admission, the patient’s temperature rose to 38.7 “C, and her serum glucose increased to 211 mg/dL. Ampicillin (1 g q4h) was started. On hospital day 2, the hypogastrium increased in prominence and placement of a Foley catheter with pressure over the bladder released a large amount of air. Blood cultures drawn that day were positive for C. perfringens at forty-eight hours, and aerobic urine cultures were negative. Treatment was changed to intravenous penicillin G, 6.7 units q4h, on hospital day 4. A cystogram several days later showed trabeculated bladder without evidence of vesicocolic or vesicovaginal
UROLOGY
I
MAY 1993 / VOLUME
41, NUMBER 5
FIGURE1. Plain film of abdomen shows markedly distended gas-filled bladder. Thin line of gas shown within bladder wall throughout its circumference.
fistula. Renal and pelvic sonogram findings were normal. The patient became afebrile on hospital day 10; her mentation improved, the serum glucose fell to 125 mg/dL, and blood urea nitrogen, serum creatinine, and white blood cell count all returned to normal levels. The stool became positive for occult blood, and colonoscopy showed hemorrhoids but no evidence of a fistula to the bladder. Comment Emphysematous cystitis is caused by gasforming organisms in the bladder. Gas, particularly carbon dioxide, may be formed in either the bladder wall or lumen, or in both locations. To date, 165 cases have been reported in the literature.‘-lg Gas may also enter the bladder from a fistula, from penetrating trauma, or following surgery or bladder instrumentation. l In 1961, Bailey2 noted that predisposing factors in 71 cases of emphysematous cystitis included glycosuria, particularly diabetes, lower urinary tract obstruction/urinary retention. There was often a history of chronic urinary
UROLOGY
/ MAY 1993
/ VOLUME
41, NUMBER5
tract infectionB3 The incidence in women was approximately twice that in men. Holesh4 reviewed 118 cases in 1969. Most of the patients were elderly, 58 were diabetics, and the average duration of their diabetes was fourteen years. Diabetes may be well controlled when emphysematous cystitis presents.5 Patients with emphysematous cystitis complain of frequency, urgency, nocturia, dysuria, or occasionally, pneumaturia. Urinalysis usually shows pyuria and hematuria in addition to glycosuria/ketonuria, suprapubic tenderness, and if the bladder is enlarged, it is usually palpable. 2.4,6 E. coli is the most common organism from the urine in emphysematous cystitis; less frequently, Enterobacter aerogenes, Staphylococcus aureus, streptococci, Klebsiella pneumoniae, Proteus mirabilis, Nocardia, or Candida albicans have been isolated from the urine.2.7-g While computerized tomography (CT) is a sensitive means of detecting gas in the bladder, a plain abdominal radiograph may be diagnostic.‘O A thin radiolucent line of streaks or gas bubbles may outline the bladder wall. These bubbles may have a “cobblestone” appearance when seen “en face.“2 The bladder wall may thicken and the gas coalesce into blebs or spheres, forming a “beaded necklace.“2,eJ1 Air also may be seen in the bladder lumen, with an air-fluid level on films with patient in erect position. Intravenous urography or retrograde cystography shows filling defects in the bladder if gas is present in its walls.g Within several days the gas usually disappears from radiographs.2 Cystoscopy is also diagnostic. Burns12 described finding numerous tiny gas bubbles embedded in a shaggy reddened bladder wall. Others have noted that these bubbles ruptured easily and gave off an exaggerated or silvery light reflex.6x11 C. perfringens is ubiquitous in soil and in the human intestinal tract. It causes soft tissue, intra-abdominal, and female genital tract infections, food poisoning, enteritis necroticans, and pulmonary infections. It is usually only one component of the flora in a polymicrobial infection. Gas formation occurs in only a minority of cases.13 Clostridium or other anaerobes rarely cause urinary tract infections. Anaerobes may be found at the urethral meatus and a positive anaerobic culture’s significance is not always clear.14.15 Headington and Beyerlein16 reported that only 158 anaerobes grew from 15,250
459
clean-catch midstream or catheterized urine specimens, including 57 species of Clostridia. Only 7 patients had symptoms of urinary tract infection and anaerobic isolates on pure culture (including two isolates of C. perfringens) . In no case could the infections be attributed to the anaerobes alone. Gorbach and Thadepalli” reviewed a series of 114 isolates of Clostridia. Other than a prostatic abscess, none involved the urinary tract. Nielsen and LaurserP reported a case of C. perfringens cystitis, without emphysematous changes, in an elderly diabetic woman. Our case is one of several in the literature associating C. perfringens with emphysematous cystitis. Levi+ described the first case in 1938, a fifty-seven-year-old woman with poorly controlled diabetes. The diagnosis was confirmed by cystoscopy and a positive urine culture. BurnsI reported the second case, a seventytwo-year-old woman without a diabetic history; however, E. coli and fi-hemolytic streptococci as well as C. perfringens grew from the urine. Wayland and Kiviat7 reported 2 cases with C. perfringens bacteremia, an eightyyear-old man and a sixty-two-year-old woman, both diabetics. Anaerobic urine cultures were not done in either case, but aerobic urine cultures were negative. Maliwan15 reported on a thirty-eight-year-old woman without diabetes with positive blood cultures. Again, anaerobic urine cultures were not obtained. Finally, West, Holley, and Lauer14 reported on a seventy-twoyear-old woman with well-controlled diabetes, with a positive urine culture. No urine Gram stain or anaerobic urine cultures were obtained from our patient. However, no explanation for emphysematous cystitis other than C. perfringens is plausible in view of negative aerobic urine cultures and C. perfringens bacteremia. Three of the previous cases also had positive blood cultures and negative aerobic urine cultures, and anaerobic urine cultures were not performed. Though it may be difficult to clearly associate positive clostridial blood cultures with concurrent infectious processes, gas production in this case links Clostridia to the cystitis. The pathogenesis of emphysematous cystitis in this case and in general is not clear. Sugar in
460
the urine may provide a reducing environment for anaerobic growth. The neurogenic bladder common in diabetics contributes to bladder distention and urinary retention; a distended bladder may have decreased ~0, in the urothelium, which may promote the growth of anaerobes. C. perfringens, as opposed to other clostridial species, can tolerate a low p02 of up to 90 mm
Hg*
Treatment of emphysematous cystitis includes control of diabetes, relief of urinary obstruction, and use of appropriate antibiotics. Infectious Disease Division Winthrop-University Hospital Mineola, New York 11501 (DR. CUNHA) References 1. Elkin M: Radiology of the urinary system, Boston, Little Brown & Co., ~012, 1980, pp 209, 217-221, 262-267. 2. Bailey H: Cystitis emphysematosa, AJR 86: 850 (1961). 3. LeDec A, Cariou G, and Jeaneau PL: Case profiles: cystitis emphysematosa, Urology 25: 88 (1985). 4. Holesh S: Gas in the bladder-cystitis emphysematosa, Clin Radio1 20: 234 (1969). 5. Vasumoto R, Asakawa M, and Nishisaka N: Emphysematous cystitis, Br J Uro163: 644 (1988). 6. Hawtrey CE, Williams JJ, and Schmidt JD: Cystitis emphysematosa, Urology 4: 612 (1974). 7. Wayland JS, and Kiviat MD: Clostridial cystitis emphysematosa, Urology 4: 601 (1974). 8. Bartkowski DP, and Lane&y JR: Emphysematous prostatitis and cystitis secondary to Candida albicans, J Urol 139: 1063 (1988). 9. Singh CR, and Lytle WF Jr: Cystitis emphysematosa caused by Candida albicans, J Urol 130: 1171 (1983). 10. Bohlman ME, Fishman EK, Oesterling JE, and Goldman SM: CT findings in emphysematous cystitis, Urology 32: 63 (1988). 11. Ellenbogen EH, and Talner LB: Uroradiology of diabetes mellitus, Urology 4: 413 (1974). 12. Burns RA: Cystitis emphysematosa, a case report, J Urol 49: 808 (1943). 13. Bartlett JG: Gas gangrene (other Clostridium-associated diseases), in Mandell GL, Douglas RG Jr, and Bennett JE (Eds): Principles and Practice of Infectious Diseases, New York, Churchill Livingstone, 1990, pp 1850-1858. 14. West TE, Holley HP Jr, and Lauer AD: Emphysematous cystitis due to clostridium perfringens, JAMA 246: 363 (1981). 15. Maliwan N: Emphysematous cystitis associated with Clostridium perfringens bacteremia, J Urol 121: 819 (1979). 16. Headington JT, and Beyerlein B: Anaerobic bacteria in routine urine culture, J Clin Path01 19: 573 (1966). 17. Gorbach SL, and Thadepahi H: Isolation of Clostridium in human infections: evaluation of 114 cases, J Infect Dis 131: S81 (1975). 18. Nielsen ML, and Laursen H: Clostridial infection in the urinary tract, Stand J Urol Nephro16: 120 (1972). 19. Levin HA: Gas cysts of urinary bladder, J Urol 39: 45 (1938).
UROLOGY
I
MAY 1993
I
VOLUME41,
NUMBER5