Vol. 59, No. I Printed in U.S.A.
GASTROENTEROLOGY
Copyri ght © 1970 by The Williams & Wilkins Co.
BACTEREMIA FOLLOWING PERORAL BIOPSY OF THE SMALL INTESTINE ARTHUR
M.
PETTY,
M.D.,
AND JULIUS WENGER,
M.D.
Department of M edicine, Emory University School of Medicine, and the Veterans Administration Hospital, Atlanta, Georgia
A case of a rare complication of small bowel biopsy is presented. Fever, nausea, and bacteremia occurred within 72 hr after a successful jejunal biopsy. No other source of gram-negative bacteremia was apparent; a high colony count of enteric organisms had been present 4 months previously in both gastric and jejunal cultures. A rapid return to the prebiopsy state occurred following gastric suction, intravenous alimentation, and antibiotic therapy. This complication must be considered in performing intestinal biopsies in cachectic patients, particularly those with bacterial overgrowth in the small bowel. Many reports confirm the value of peroral jejunal biopsy. The hazards of this procedure have been reviewed by Rubin and Dobbins. 1 Bacteremia has not been reported as a complication following this procedure. A clinical syndrome which began 24 hr after peroral biopsy of the jejunum is described herein; it was characterized by fever, nausea, and abdominal pain, with all symptoms and signs subsiding rapidly after antibiotic therapy. The duration of this episode was 7 days. Case Report W. Y., 256-16-1717, was a 62-year-old man. Perforation of a duodenal ulcer occurred in 1951; partial gastric resection, gastrojejunostomy, and vagotomy were performed in 1954. Following the surgery he lost weight and never regained normal nutrition. fu 1963, he was admitted for diarrhea, bloating, and occasional cramping abdominal pain with radiation of pain posteriorly. Studies revealed an abnormal radioactive triolein excretion but a normal xylose tolerance. A mild degree of carb.ohydrate intolerance was present. The patient had hypoproteinemia and moderate anemia, with a few target cells and macrocytes Received September 30, 1969. Accepted January 26, 1970.
Address requests for reprints to: Dr. Julius Wenger, Medical Service, Veterans Administration Hospital, Atlanta, Georgia 30329. 140
in the peripheral blood smear. Bone marrow examination revealed normal iron stores and erythroid hyperPlasia (tables 1 and 2). A small intestinal biopsy showed a few blunted villi but was otherwise normal. He was thought to have pancreatic insufficiency secondary to gas· tric surgery and was treated with a low fat diet, pancreatic extract, Cotazyme (pancrelipase, Organon, Inc., West Orange, N . J., 2 capsules four times daily) , and vitamin B,2 in· jections. The abnormality of vitamin B,2 ab· sorption was not explained, particularly as it was not corrected by intrinsic factor. In ret· rospect, it perhaps represented deficiency of a pancreatic factor required for optimal vitamin B1 2 absorPtion. 2 ' 3 He responded well to this therapy for several years, but ceased taking his medications and again was hospitalized in January 1968 for weight loss and several weeks of diarrhea. Laboratory studies are summa· rized in tables 1 and 2. Cultures of the stom· ach and small intestinal contests revealed an excessive number of bacterial colonies; he was treated with Polycillin (ampicillin trihydrate, Bristol Laboratories, Syracuse, N. Y.), 250 mg orally four times daily for 1 week. The cultures were repeated (table 3) and there was no change in the intestinal bacteria. The stool fat excretion was unchanged during this period. At the time of discharge from the hospital, a therapeutic regimen was prescribed similar to the one given in 1963. fu April 1968, the patient again was hospi· talized for a fracture of the right femur. He was very thin and pale ; there was edema oi
July 1970
141
CASE REPORTS Serial laboratory determinations
TABLE 1
Evidence of malnutrition
Body weight (lb) Hematocrit (ml/100 ml) . . . . . . . .. . . . . . . . . Total serum protein (g/ 100 ml) . . . . . .. . . ' .. . .. . Serum albumin (g/100 ml) . . . . . . . . .. . . . . Serum carotene (.ug/100 ml) . ..
TABLE
2. Studies of absorption
T iming of studies
Glucose. 1963
Xylose, 1963
min
mg/100 ml
mg/1 00 ml
Fasting 30 60 120 180
69 274 272 142 85
Urine output/ 5 hr
59.2 57.8 50.0 6.7 g
Vita min B ., absorption (Schilling test) , 1963
Part I. Urinary recovery of oral dose of Cyanocobalamin (Co" ) Part II. Urinary recovery of oral dose of Cyanocobalamin (Co57) administered with added intrinsic factor
2.0 3.0
Qua n titative feca l excretion stud ies (72-hr collections)
Triolein (I' "') (1963) Total lipids (March 4, 1968) Total lipids (March 12, 1968)
46% of oral dose 15.0 g/24 hr 17.1 g/24 hr
both legs . A blood smear was identical with that of 1963, the serum iron was 61 llg per 100 ml, and the total iron binding capacity was 107 llg per 100 ml. Other laboratory studies were unchanged from those during the prior hospital admissions (table 1). Small intestinal biopsy specimens were obtained on July 23, 1968, using the multipurpose biopsy tube (Quinton Instrument Company, Seattle, Washington) with a capsule with four suction ports. A negative pressure of 24 inches of mercury was employed as suggested by Dr. C. E. Rubin (personal communication). The tube was placed in the proximal jejunum and three specimens were obtained with a single application of suction. Microscopic examination showed a few moderately broad villi and some thinning of the mucosa, but no lesions consistent with celiac disease.
1953
1957
1963
January 1968
June 1968
167
154 44
145 38 4.6-5.5 2.4-3 .2 28
133 36 5.7 2.6 19
156 35 4.8 1.6 14
166
Twenty-four hours after the biopsy the patient developed anorexia and vomited food twice. Forty-eight hours after the biopsy the patient complained of nausea, and vomited again; a temperature of 98 F was recorded. All prior temperature measurements had been normal. The next day he reported generalized abdominal pain. Some tenderness was noted and bowel sounds were absent, but there was no evidence of subphrenic air collection or of peritonitis. The temperature was 102.4 F. Blood and urine cultures were obtained and Keflin (sodium cephalothin, Eli Lilly and Company, Indianapolis, Ind.) , 4.0 g per day, and Kantrex (kanamycin sulfate injection, Bristol Laboratories, Syracuse, N . Y.), 1.0 g per day, were administered. The blood cultures revealed Escherichia coli, sensitive t o most common antibiotics and resistant to sulfisoxazole and tetracycline. During the antibiotic treatment, continuous nasogastric suction and intravenous fluids were also administered; oral feedings were discontinued. After 4 days of this regimen the patient recovered his appetite, the abdominal tenderness disappeared, and he resumed his usual hospital diet. Keflin and Kanamycin were discontinued and Polycillin, 0.5 g, was given orally every 6 hr for 10 days. This short lived episode, occurring 48 to 72 hr after a small intestinal biopsy, suggests a cause and effect relationship. No similar episode was recorded during the patient's prior hospitalizations. Despite vitamin supplements, MCT oil (medium chain triglycerides oil, Mead Johnson Laboratories, Evansville, Ind.) a low fat diet, and pancreatic extract (Cotazyme), the patient showed little improvement in body weight or in over-all nutrition. Edema of the extremities persisted and there was no radiographic evidence of bone healing of the femur. On September 20, 1968, the patient became hypotensive and could not be resuscitated. Postmortem examination revealed pulmonary emboli, ascites, and pleural effusion, but no evidence of cardiac disease. Examination of the abdo-
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Vol. 59, No. 1
CASE REPORTS T ABLE 3 B ac t erw · logical studies Date
Source of culture
No. of organisms (colony count)
Bacteria recovered
perml
February 8, 1968
Intestine
10 X 106
March 22, 1968
Intestine, after oral ampicillin therapy Stomach
10 X 106
March 22, 1968
15 X 106
men revealed a fibrotic pancreas and a normal postoperative stomach and jejunum. The intestinal wall was thinner than normal. The liver contained an excess of fat but had no evidence of cirrhosis.
Discussion Complications of peroral biopsy of the small intestine generally are limited to perforation and hemorrhage. Neither o~ curred in this case, but nausea, abdominal distress, and fever suggested localized disease of the bowel wall with associated bacteremia. No other source of bacteremia was apparent. Urine cultures did not show a significant bacterial colony count (less than 1000 colonies per ml). Four months earlier, the intestinal contents had shown a high colony count of gram-negative bacilli of the Klebsiella-Aerobacter group (greater than 10 million colonies per ml). However, the blood cultures taken during the febrile episode after biopsy, revealed a predominant growth of E. coli. A repeat culture of the small intestinal contents was not obtained; anaerobic cultures were not obtained. Despite the difference between the intestinal cultures and the blood cultures, both Klebsiella-Aerobacter and E. coli are abnormal organisms in the upper jejunum, particularly when present in large numbers. 4 Although definite proof of bacterial transfer from jejunal lumen to blood cannot be documented, the unusual nature of this complication prompted this report. This patient had had no fever or abdominal distress during a long illness characterized by malnutrition and diarrhea. Seventy-two hours following intestinal biopsy there was nausea, vomiting, and absence of bowel
Klebsiella-Aerobacter. Sensitive to most common antibiotics. Resistant to sulfisoxazole Klebsiella-Aerobacter. Sensitive to most common antibiotics Same organisms as intestinal culture, March 22 1968
sounds, without evidence of hemorrhage or of free perforation. Of course, a delayed incomplete penetration of the bowel wall might have occurred and initiated bacteremia due to enteric organisms. Within 4 days after the institution of gastric suction, intravenous fluid administration and antibiotic therapy, the entire clinical syndrome was reversed. The bacilli demonstrated in the small bowel mucosa of patients with Whipple's disease have not yet been able to be cultured. It is interesting to compare our patient with a case reported by Trier et al. 5 Their patient had several episodes of fever which occurred after biopsy of the small bowel mucosa; following antibiotic therapy, when the organisms were no longer visible in the mucosal biopsies, febrile episodes no longer occurred. In the postbiopsy syndrome, fever and abdominal pain are also present, but this clinical picture generally occurs during the biopsy procedure or within 6 to 12 hr after the biopsy tube is removed. 6 Blood cultures have shown no bacterial growth in the postbiopsy syndrome; thus, we do not feel that this explains our case. The positive blood cultures obtained from our patient suggest that a mucosal biopsy can initiate the passage of bacteria from jejunal lumen to the systemic circulation. REFERENCES 1. Rubin CE, Dobbins WO: Peroral biopsy of the small intestine. Gastroenterology 49:676-697, 1965
2. Veeger WL, Abels J, Hellemans N, et al: Effect of sodium bicarbonate and pancreatin on the absorption of vitamin B12 and fat in pancreatic insufficiency. New Eng J Med 267:1341-1344, 1962 3. Toskes PP, Hansel JJ, Cerda JJ, et al: Studies of
Jul_y 1970
CASE REPORTS
the role of the pancreas in vitamin B12 absorption (abstr). Clin Res 17:529, 1969 4. Kaiser MH, Cohen R, Arteaga I, et al: Normal viral and bacterial flora of the human small and large intestine. New Eng J Med 274:500-505; 558563, 1966 5. Trier JS , Phelps PC, Eidelman S, et al: Light and
143
electron microscope correlation of jejunal mucosal histology with antibiotic treatment and clinical status. Gastroenterology 48:684- 707, 1965 6. Flick AL, Quinton WE, Rubin CE: A peroral hydraulic biopsy tube for multiple sampling at any level of the gastrointestinal tract. Gastroenterology 40:120-126, 1961