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Fatal Non-01 Vibrio cholerae Septicemia in Chronic Lymphocytic Leukemia
GASTROENTEROLOGY 1982;83:1130-1
Fatal Non-01 Vibrio cholerae Septicemia in Chronic Lymphocytic Leukemia MARK I. SIEGEL and ARVEY I. ROGERS Division of Gastroenterology, Department of Medicine, University of Miami School of Medicine and Veterans Administration Medical Center, Miami, Florida
The potential of non-01 Vibrio cholerae as human pathogens is assuming greater clinical importance. They are also capable of producing a spectrum of illness that is not confined to the gastrointestinal or biliary tracts. We report a case offatal non-01 Vibrio cholerae septicemia in a patient with chronic lymphocytic leukemia. Non-01 Vibrio cholerae are morphologically and biochemically indistinguishable from classical V. cholerae, but are serologically distinct (1). Marine vibrios, Vibrio parahemolyticus, and Campylobacter (formerly Vibrio) fetus are excluded by this definition. Non-01 V. cholerae may produce infection confined to the gastrointestinal system indistinguishable from classical cholera. They may also be cultured from the stool of individuals without any apparent symptoms, or with only very mild diarrhea (2). Unlike V. cholerae which does not cause infection outside the gastrointestinal and biliary tracts, these non-O! V. cholerae can produce systemic infection, commonly in the debilitated and immunocompromised patient. We report a case of fatal non01 V. cholerae septicemia which followed seafood consumption in a. patient with chronic lymphocytic leukemia (eLL). Earlier reports have emphasized the gastroenteritic features of the illness. In our case, sepsis was the predominant feature.
Case Report A 51-yr-old man, with an 8-yr history of CLL was admitted to a local hospital. He had been asymptomatic on therapy consisting of intermittent leukapheresis and packed red cell transfusions with a chemotherapeutic regimen of prednisone, fluoxymesterone, and chlorambuReceived August 27, 1981. Accepted June 23, 1982. Address requests for reprints to: Arvey 1. Rogers, M.D., Division of Gastroenterology, Veterans Administration Medical Center, 1201 NW 16th Street, Miami, Florida 33125. © 1982 by the American Gastroenterological Association 0016-5085/82/111130-02$02.50
cil. A complete blood count (CBC) done 2 days before admission showed a hematocrit of 21 %, white cell count of 121,000/mm3 , and platelets of 55,000/mm 3 . On the evening before admission he had eaten raw oysters in a local South Broward County Florida restaurant. On the morning of admission he was awakened at 5 AM with vomiting, nonwatery diarrhea, and a shaking chill. In the emergency room at 8 AM, he had complained of dyspnea, and pain on the right side of the chest. Diarrhea had ceased and was not noted again throughout the hospitalization. The patient denied recent travel or salt water bathing. Physical examination revealed the patient to be alert and oriented, in acute respiratory distress, and dehydrated with a cyanotic hue to his face and nail beds. Vital signs recorded a rectal temperature of 37.5°C, a regular tachycardia of 140/min, tachypnea of 50 cycles/min, and hypotension to a level of 80/50 mmHg. There was left supraclavicular adenopathy. On chest exam, the right mid- and lower lung fields were dull to percussion with diminished breath sounds and rales. His abdomen was soft and nontender without distention. Liver and spleen were enlarged but unchanged from previous exams. Bowel sounds were active. No stool was present on digital examination of rectum. A chest film showed a right mid- and lower lobe infiltrate. An EKG demonstrated sinus tachycardia. A complete blood count now showed a white cell count of 250,000/mm 3 , almost entirely lymphocytes. The hematocrit had increased to 31.1 % and platelets were 50,000/ mm 3 • Blood, sputum, and urine cultures were obtained. Serum electrolytes were normal except for a carbon dioxide of 17 mmollL. The blood urea nitrogen (BUN) was 17 mg/dl. Prothrombin (PT) and partial thromboplastin (PTT) times were normal on admission. Initial urine specific gravity was 1.014. He soon required intubation and ventilator assistance for hypoxemia and respiratory distress. The initial diagnoses were pneumonia and moderate to severe dehydration in a compromised host. He was begun on tobramycin, cefoxitin, erythromycin, ticarcillin, and trimethoprim-sulfa. He received methyl prednisolone and several transfusions of packed red blood cells. Over the initial 24-h period he required 7 L of fluids intravenously to correct central venous and pulmonary artery wedge pressures. Dopamine was instituted for oliguria. Progressive abdominal distention with absence of bowel sounds
NONCHOLERA VIBRIO SEPTICEMIA
November 1982
was noted. By the second day. sputum and blood cultures were growing a gram-negative rod sensitive to ampicillin. chloramphenicol. cefoxitin. tetracycline. carbenicillin. gentamicin. and trimethoprim-sulfa. He lapsed into coma and developed severe metabolic acidosis accompanied by disseminated intravascular coagulation (DIC). Disseminated intravascular coagulation was manifested by a drop in platelets to 10.000/mm3. prolongation of PT to 50% of control and PTT to 58 s (normal, <40 s), and the appearance of fibrin degradation products in the serum. Late that day acute renal failure was evident with BUN climbing to 48 mg/dl. creatinine 4.7 mg/dl. and potassium 7.4 mmol. A trough tobramycin level was 3.9 JLg/ml (therapeutic range 3-10 JLg/ml). Hemodialysis was instituted. On the afternoon of the third hospital day. he suffered a cardiac arrest and expired. No autopsy was performed. The organism was subsequently identified as non-01 V. cholerae. Smith serotype 17 by the Florida State Board of Health and the Center for Disease Control (CDC). Enzymelinked immunosorbent assay (3) for heat-labile and infant mouse assay (4) for heat-stable enterotoxins were negative. * No other cases could be traced to the raw oysters at the restaurant.
Discussion Septicemia is uncommon following oral ingestion of non-Ol V. cholerae. In a recent study (5) of non-Ol V. cholerae gastroenteritis, only 1 of 14 sporadic cases had associated septicemia, and no deaths were reported. Extraintestinal isolation appears to be of more serious consequence. In another study (1), 4 of 9 patients died with non-Ol V. cholerae isolation from sites other than stool, gastrointestinal tract, or biliary tract. Death was attributable to septicemia in 3 of these 4, all of whom had occupational or recreational salt water exposure. Extraintestinal isolation of non-Ol V. cholerae has been associated with significant underlying diseases, including carcinoma, subtotal gastrectomy, mongolism, cirrhosis, acute monocytic leukemia, and salt water drowning (1). To our knowledge, this is the first report of non-Ol V. cholerae septicemia in a patient with CLL. Death in patients with CLL usually is caused by uncontrolled infection (6). Hypoglobulinemia and agammaglobulinemia are common in advanced CLL (7). Gut immunoglobulins * Performed by the Center for Disease Control in Atlanta. Ga.
1131
have been postulated to mediate vibrio destruction, perhaps by interfering with vibrio attachment to gut epithelium or by impairing vibrio motility (8). Diarrhea in our patient occurred in the absence of detectable enterotoxin. When detectable, enterotoxin is antigenic ally similar to that of V. cholerae. The pathogenic mechanism for diarrhea in nontoxigenic strains is not well defined. When the gastroenteritic form of illness is encountered, therapy should be directed toward vigorous fluid and electrolyte replacement to avoid hypovolemic complications. If an ileus occurs, as in our case, shock and dehydration may be present without diarrhea (8). The role of antibiotics in treatment of non-Ol V. cholerae infections is unclear but they may shorten the duration of diarrhea. Tetracycline may be preferred for gastroenteritis but most isolates are also susceptible to kanamycin, gentamicin, ampicillin, chloramphenicol, and cephalothin (5). Currently, there are no conclusive recommendations regarding the antibiotic of choice. If septicemia occurs, underlying disease may be the most important determinant of outcome. Intractable shock may occur despite careful attention to volume replacement and institution of appropriate antibiotics.
References 1. Hughes JM. Hollis DG. Gangarosa EJ, et at. Non-cholera vibrio
infections in the United States. Ann Intern Med 1978;88:6026.
2. Zafari Y. Zarifi AZ. Rahmanzadeh S. et at. Diarrhea caused by nonagglutinable Vibrio cholerae (non-cholera vibrio) . Lancet 1973;ii:429-30. 3. Yolken RH. Greenberg HB. Merson MH. et al. Enzyme-linked immunosorbent assay for detection of Escherichia coli heatlabile enterotoxin. J Clin Microbial 1977;6:439-44. 4. Dean AG, Ching Ye, Williams RG , et al. Test for E. coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. JInfect Dis 1972;125:407-11. 5. Morris JG Jr, Wilson R, Davis BR, et al. Non-O group 1 Vibrio cholerae gastroenteritis in the United States. Ann Intern Med 1981;94:656-8. 6. Boggs DR. Sofferman SA, Wintrobe MM, et at. Factors influencing the deviation of survival of patients with chronic lymphocytic leukemia. Am J Med 1966;40:243-54. 7. Wintrobe MM. Clinical hematology. 7th ed. Philadelphia: Lea and Febiger, 1974:1396. 8. Greenough WB. Vibrio cholerae. In: Mandell GM, Douglas RG, Bennett J. eds. Principles and practice of infectious diseases. New York: Wiley & Sons, 1979;1672-87.
Fatal Non-01 Vibrio cholerae Septicemia in Chronic Lymphocytic Leukemia MARK I. SIEGEL and ARVEY I. ROGERS Division of Gastroenterology, Department of Medicine, University of Miami School of Medicine and Veterans Administration Medical Center, Miami, Florida
The potential of non-01 Vibrio cholerae as human pathogens is assuming greater clinical importance. They are also capable of producing a spectrum of illness that is not confined to the gastrointestinal or biliary tracts. We report a case offatal non-01 Vibrio cholerae septicemia in a patient with chronic lymphocytic leukemia. Non-01 Vibrio cholerae are morphologically and biochemically indistinguishable from classical V. cholerae, but are serologically distinct (1). Marine vibrios, Vibrio parahemolyticus, and Campylobacter (formerly Vibrio) fetus are excluded by this definition. Non-01 V. cholerae may produce infection confined to the gastrointestinal system indistinguishable from classical cholera. They may also be cultured from the stool of individuals without any apparent symptoms, or with only very mild diarrhea (2). Unlike V. cholerae which does not cause infection outside the gastrointestinal and biliary tracts, these non-O! V. cholerae can produce systemic infection, commonly in the debilitated and immunocompromised patient. We report a case of fatal non01 V. cholerae septicemia which followed seafood consumption in a. patient with chronic lymphocytic leukemia (eLL). Earlier reports have emphasized the gastroenteritic features of the illness. In our case, sepsis was the predominant feature.
Case Report A 51-yr-old man, with an 8-yr history of CLL was admitted to a local hospital. He had been asymptomatic on therapy consisting of intermittent leukapheresis and packed red cell transfusions with a chemotherapeutic regimen of prednisone, fluoxymesterone, and chlorambuReceived August 27, 1981. Accepted June 23, 1982. Address requests for reprints to: Arvey 1. Rogers, M.D., Division of Gastroenterology, Veterans Administration Medical Center, 1201 NW 16th Street, Miami, Florida 33125. © 1982 by the American Gastroenterological Association 0016-5085/82/111130-02$02.50
cil. A complete blood count (CBC) done 2 days before admission showed a hematocrit of 21 %, white cell count of 121,000/mm3 , and platelets of 55,000/mm 3 . On the evening before admission he had eaten raw oysters in a local South Broward County Florida restaurant. On the morning of admission he was awakened at 5 AM with vomiting, nonwatery diarrhea, and a shaking chill. In the emergency room at 8 AM, he had complained of dyspnea, and pain on the right side of the chest. Diarrhea had ceased and was not noted again throughout the hospitalization. The patient denied recent travel or salt water bathing. Physical examination revealed the patient to be alert and oriented, in acute respiratory distress, and dehydrated with a cyanotic hue to his face and nail beds. Vital signs recorded a rectal temperature of 37.5°C, a regular tachycardia of 140/min, tachypnea of 50 cycles/min, and hypotension to a level of 80/50 mmHg. There was left supraclavicular adenopathy. On chest exam, the right mid- and lower lung fields were dull to percussion with diminished breath sounds and rales. His abdomen was soft and nontender without distention. Liver and spleen were enlarged but unchanged from previous exams. Bowel sounds were active. No stool was present on digital examination of rectum. A chest film showed a right mid- and lower lobe infiltrate. An EKG demonstrated sinus tachycardia. A complete blood count now showed a white cell count of 250,000/mm 3 , almost entirely lymphocytes. The hematocrit had increased to 31.1 % and platelets were 50,000/ mm 3 • Blood, sputum, and urine cultures were obtained. Serum electrolytes were normal except for a carbon dioxide of 17 mmollL. The blood urea nitrogen (BUN) was 17 mg/dl. Prothrombin (PT) and partial thromboplastin (PTT) times were normal on admission. Initial urine specific gravity was 1.014. He soon required intubation and ventilator assistance for hypoxemia and respiratory distress. The initial diagnoses were pneumonia and moderate to severe dehydration in a compromised host. He was begun on tobramycin, cefoxitin, erythromycin, ticarcillin, and trimethoprim-sulfa. He received methyl prednisolone and several transfusions of packed red blood cells. Over the initial 24-h period he required 7 L of fluids intravenously to correct central venous and pulmonary artery wedge pressures. Dopamine was instituted for oliguria. Progressive abdominal distention with absence of bowel sounds
NONCHOLERA VIBRIO SEPTICEMIA
November 1982
was noted. By the second day. sputum and blood cultures were growing a gram-negative rod sensitive to ampicillin. chloramphenicol. cefoxitin. tetracycline. carbenicillin. gentamicin. and trimethoprim-sulfa. He lapsed into coma and developed severe metabolic acidosis accompanied by disseminated intravascular coagulation (DIC). Disseminated intravascular coagulation was manifested by a drop in platelets to 10.000/mm3. prolongation of PT to 50% of control and PTT to 58 s (normal, <40 s), and the appearance of fibrin degradation products in the serum. Late that day acute renal failure was evident with BUN climbing to 48 mg/dl. creatinine 4.7 mg/dl. and potassium 7.4 mmol. A trough tobramycin level was 3.9 JLg/ml (therapeutic range 3-10 JLg/ml). Hemodialysis was instituted. On the afternoon of the third hospital day. he suffered a cardiac arrest and expired. No autopsy was performed. The organism was subsequently identified as non-01 V. cholerae. Smith serotype 17 by the Florida State Board of Health and the Center for Disease Control (CDC). Enzymelinked immunosorbent assay (3) for heat-labile and infant mouse assay (4) for heat-stable enterotoxins were negative. * No other cases could be traced to the raw oysters at the restaurant.
Discussion Septicemia is uncommon following oral ingestion of non-Ol V. cholerae. In a recent study (5) of non-Ol V. cholerae gastroenteritis, only 1 of 14 sporadic cases had associated septicemia, and no deaths were reported. Extraintestinal isolation appears to be of more serious consequence. In another study (1), 4 of 9 patients died with non-Ol V. cholerae isolation from sites other than stool, gastrointestinal tract, or biliary tract. Death was attributable to septicemia in 3 of these 4, all of whom had occupational or recreational salt water exposure. Extraintestinal isolation of non-Ol V. cholerae has been associated with significant underlying diseases, including carcinoma, subtotal gastrectomy, mongolism, cirrhosis, acute monocytic leukemia, and salt water drowning (1). To our knowledge, this is the first report of non-Ol V. cholerae septicemia in a patient with CLL. Death in patients with CLL usually is caused by uncontrolled infection (6). Hypoglobulinemia and agammaglobulinemia are common in advanced CLL (7). Gut immunoglobulins * Performed by the Center for Disease Control in Atlanta. Ga.
1131
have been postulated to mediate vibrio destruction, perhaps by interfering with vibrio attachment to gut epithelium or by impairing vibrio motility (8). Diarrhea in our patient occurred in the absence of detectable enterotoxin. When detectable, enterotoxin is antigenic ally similar to that of V. cholerae. The pathogenic mechanism for diarrhea in nontoxigenic strains is not well defined. When the gastroenteritic form of illness is encountered, therapy should be directed toward vigorous fluid and electrolyte replacement to avoid hypovolemic complications. If an ileus occurs, as in our case, shock and dehydration may be present without diarrhea (8). The role of antibiotics in treatment of non-Ol V. cholerae infections is unclear but they may shorten the duration of diarrhea. Tetracycline may be preferred for gastroenteritis but most isolates are also susceptible to kanamycin, gentamicin, ampicillin, chloramphenicol, and cephalothin (5). Currently, there are no conclusive recommendations regarding the antibiotic of choice. If septicemia occurs, underlying disease may be the most important determinant of outcome. Intractable shock may occur despite careful attention to volume replacement and institution of appropriate antibiotics.
References 1. Hughes JM. Hollis DG. Gangarosa EJ, et at. Non-cholera vibrio
infections in the United States. Ann Intern Med 1978;88:6026.
2. Zafari Y. Zarifi AZ. Rahmanzadeh S. et at. Diarrhea caused by nonagglutinable Vibrio cholerae (non-cholera vibrio) . Lancet 1973;ii:429-30. 3. Yolken RH. Greenberg HB. Merson MH. et al. Enzyme-linked immunosorbent assay for detection of Escherichia coli heatlabile enterotoxin. J Clin Microbial 1977;6:439-44. 4. Dean AG, Ching Ye, Williams RG , et al. Test for E. coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. JInfect Dis 1972;125:407-11. 5. Morris JG Jr, Wilson R, Davis BR, et al. Non-O group 1 Vibrio cholerae gastroenteritis in the United States. Ann Intern Med 1981;94:656-8. 6. Boggs DR. Sofferman SA, Wintrobe MM, et at. Factors influencing the deviation of survival of patients with chronic lymphocytic leukemia. Am J Med 1966;40:243-54. 7. Wintrobe MM. Clinical hematology. 7th ed. Philadelphia: Lea and Febiger, 1974:1396. 8. Greenough WB. Vibrio cholerae. In: Mandell GM, Douglas RG, Bennett J. eds. Principles and practice of infectious diseases. New York: Wiley & Sons, 1979;1672-87.