knowledge of the clinical presentation and patho- genetic features of C. .... Simon etal: J. of Clinical Gastroenterology 1986; 8 (3): 482-487.7. Jensen etal: New.
Campylobacter fetus cholangitis and bacteremia James Douketis, MD Donald E. Low, MD, FRCPC
M ost cases of Campylobacter infections occur as a self-limiting diarrheal illness in young, previously healthy people and are usually due to Campylobacterjejuni.1'2 Systemic illness with bacteremia is uncommon, accounting for less than 1% of all reported cases of Campylobacter infection.3 The pathogen in those cases is usually C. fetus subspecies fetus. The infected patients are often debilitated and have a pre-existing chronic disease associated with immune compromise.3'4 In such cases a diarrheal illness may coexist.5 We believe this is the first case of C. fetus cholangitis with bacteremia in a patient with no demonstrable evidence of immune compromise. This case not only serves to broaden our knowledge of the clinical presentation and pathogenetic features of C. fetus infections but also illustrates that such infections may not always occur in immune-compromised hosts. Case report
A 74-year-old man was admitted to hospital after 3 days of abdominal pain and 1 day of fever, chills and jaundice. In 1980 he had had a cholecystectomy for symptomatic choledocholithiasis and a sigmoidectomy for colonic carcinoma. There had been no clinical or endoscopic evidence of recurrence of the tumour. The man described the pain as gradual in onset, occurring 1 to 2 hours after a meal. It was continuous, dull and aching, located in the periumbilical region and associated with nausea. On the day of admission to hospital he noted that his urine was brown and his stools were pale. He denied any recent history of other abdominal pain or jaundice, weight loss or changes in bowel habits. He had no history of alcohol abuse and had not recently been exposed to blood products. The patient did not appear acutely ill but had jaundice and scleral icterus. His temperature was
From the Department of Medicine, Toronto General Hospital, and the Department of Microbiology, Mount Sinai Hospital and University of Toronto
Reprint requests to: Dr. Donald E. Low, Department of Microbiology, Rm. 602A, Mount Sinai Hospital, 600 University Ave., Toronto, Ont. M5G 1X5
39.8°C. The abdomen was soft and nontender, with no ascites or visceromegaly. There were no signs of any infectious focus. The hemoglobin level was 150 g/L, the leukocyte count 9.1 X 109/L, the serum aspartate aminotransferase (AST) level 129 (normally 5 to 20) U/L, the serum alanine aminotransferase (ALT) level 272 (normally less than 30) U/L, the serum alkaline phosphatase (ALP) level 272 (normally 30 to 95) U/L, the conjugated bilirubin level 69 (normally less than 5) ,umol/L and the total bilirubin level 16 (normally less than 18) Mmol/L. The serum amylase and protein levels were normal. The level of carcinoembryonic antigen (CEA), a glycoprotein found in both neoplastic and normal tissues, was also normal. After blood was collected for culture ceftriaxone, 2 g/d, was given. Abdominal ultrasonography showed mild fatty infiltration of the liver and a normal pancreas. Within 72 hours of admission the patient became asymptomatic, and his temperature returned to normal. Endoscopic retrograde cholangiopancreatography revealed an inflamed ampulla of Vater but normal biliary and pancreatic ducts. After 4 days of incubation the blood cultures grew C. fetus. Ceftriaxone was replaced with gentamicin, 80 mg intravenously every 8 hours. The jaundice and icterus subsided, and the AST, ALT, ALP and bilirubin levels eventually returned to normal. Stool cultures did not yield C. fetus, but the specimens had been obtained after the start of ceftriaxone therapy. The patient was discharged after 10 days of antibiotic therapy. Comments
The clinical findings in the case described here suggest that choledocholithiasis was chiefly responsible for the initial presentation and sequelae. Biliary tract obstruction by a stone resulted in biliary colic. Biliary stasis in turn was complicated by ascending cholangitis, with some degree of cholestatic hepatitis and subsequent C. fetus bacteremia. The finding of an inflamed ampulla of Vater supported the hypothesis that a stone in the biliary tract had passed spontaneously. In previous reports of C. fetus bacteremia most of the cases occurred either in infants or in people with a chronic disease state (e.g., cancer, chronic alcoholism, cirrhosis, diabetes mellitus, malnutrition, and heart and renal failure) associated with CMAJ, VOL. 141, NOVEMBER 1, 1989
925
some form of immune compromise.1'2'5 In the case presented here, despite the patient's history of colonic carcinoma, transient obstruction of the biliary tract rather than any other predisposing state was chiefly responsible for the bacteremia. The man had a normal CEA level - evidence that his colonic carcinoma had not recurred. (An elevated CEA level is found in association with a broad range of tumour types. In colorectal cancer, where it finds its chief application, the presence of an abnormal value indicates, but is not proof of, recurrence of tumour.) He had no evidence of any other disease that would have impaired his immune system. To our knowledge the only other reported case of C. fetus cholangitis with bacteremia occurred in a 47-year-old man with a history of chronic alcoholism.5 The patient's age and his aging immune system may have contributed to the pathogenesis.6 However, age in itself may not always be considered an indicator of immune system compromise, unless one can demonstrate specific deficits in the body's defence mechanisms that are responsible for pathogenesis. Most documented cases of C. fetus bacteremia have occurred in the elderly and may reflect the higher frequency of coexisting chronic disease states in this population. In 22 recently reported cases the mean age was 56 (22 to 83) years, but in 18 of the patients an immunecompromising disease state coexisted.2'5'7'8 In summary, C. fetus appears to be a microbe
that usually causes symptomatic bacteremia in patients with some form of predisposing disease. The case described here illustrates that this predisposition may not always take the form of an immune-compromised state. In addition, biliary tract infection associated with biliary stasis offers another explanation of how C. fetus may cause symptomatic bacteremia. References 1. Bokkenheuser V: Vibrio fetus infection in man. Am J Epidemiol 1970; 91: 400-409 2. Guerrant RL, Lahita RG, Winn WC: Campylobacteriosis in man: pathogenetic mechanisms and review of 91 bloodstream infections. Am JMed 1978; 65: 584-592 3. Riley LW: Results of the first year of national surveillance of Campylobacter infections in the United States. J Infect Dis 1985; 151: 956-959 4. Harvey SM, Greenwood JR: Probable Campylobacter fetus subspecies fetus gastroenteritis. J Clin Microbiol 1983; 18: 1278-1279 5. Schmidt U, Chmel H, Kaminski Z et al: The clinical spectrum of Campylobacter fetus infections: report of five cases and review of the literature. Q J Med 1980; 196: 431-442 6. Weksler ME: Biologic basis and clinical significance of immune senescence. In Rossman I (ed): Clinical Geriatrics, Lippincott, Philadelphia, 1986: 57-67 7. Ponka A, Tilvis R, Helle J et al: Infection with Campylobacter fetus. Scand JInfect Dis 1984; 16: 127-128 8. Francioli F, Herzstein J, Glob J et al: Campylobacter fetus subspecies fetus bacteremia. Arch Intern Med 1985; 145: 289-292
been a few reports of breast symptoms (swelling and/or discomfort) in men taking ranitidine; some cases have resolved on continued treatment. Symptoms and Treatment of Overdosage - No particular problems are expected followinq overdosage with Zantac. Symptomatic and supportive therapy should be given as appropriate. If need be, the drug PRESCRIBING INFORMATION may be removed from the plasma by haemodialysis. ZANTAC TABLETS (ranitidine hydrochloride) Dosage and Administration - Adults: Duodenal ulceration, benign gastric ulceration, or reflux Pharmaclogical Classification Pharmacological oesophagitis: mg once dailY at bedtime. It is not necessary to time the dose in relation to meals. In most cases of duodenal ulcer and benign Histamine H2 - receptor antagonist Indications and Clinical use gastric ulcer, healing will occur in four weeks. In the small number of patients whose ulcers may not have Zantac Tablets are indicated for the treatment of all conditions where a controlled reduction of gastric fully healed, these are likely to respond to a further course of treatment. secretion is required for the rapid relief of pain and/or ulcer healing. These include duodenal ulcerfPatients who have responded to this short term thera poarticularea those with a historm of recurrent ulcer may usefully have extended maintenance treatment at a reduced dosa e of one 150mg tablet at ulcer and reflux oes gitj.. togngastnic bedtim e Contraindlcations - Zantac is contraindicated for patients known to have hypersensitivity to the drug. To help in the management of reflux oesophagitis, the recommended course of treatment is one 300 mg Warnings - Gastric ulcer - Treatment with a histamine H2 - antagonist may mask symptoms associated tablet onc t inedaiateme or oe150smg tablet twice daily for up to 8 weeks. with carcinoma of the stomach and therefore may delay diagnosis of the condition. Accordingly, where Children: Experience with Zantac in children is limited and it has not been fully evaluated in clinical gastric ulcer is suspected the possibility of malignancy should be excluded before therapy with Zantac studren: eerecautlons. is instituted. studies - see Precautions. Precautions - Use in pregnancy and nursing mothers - The safety of Zantac in the treatment of Tablets are available as white film-coated tablets engraved ZANTAC 150 on one face Availability -onZantac conditions where a controlled reduction of gastric secretion is required during pregnancy has not been tabletsA the other, containing 150 mg ranitidine (as the hydrochloride), in packs of 30 and 60 established. Reproduction studies performed in rats and rabbits have revealed no evidence of impaired Zantac Tablets are also available as white, capsule shaped, film-coated tablets engraved ZANTAC 300 on fertility or harm to the foetus due to Zantac. If the administration of Zantac is considered to be one face and GLAXO on the other, containing 300 mg ranitidine (as the hydrochloride), in packs of 30 necessary, its use requires that the potential benefits be weighed against possible hazards to the patient tablets. and to the foetus. Ranitidine is secreted in breast milk in lactating mothers but the clinical significance of b Zantac nlection is available as 2 mL ampoules each containing 50 mg ranitidine (as the hydrochloride) in this has not been fully evaluated. 2 mL solution for intravenous or intramuscular administration. Packages of 10 ampoules. Use in Impaired renal function - Ranitidine is excreted via the kidney and in the presence of severe renal Product Monograph available on reqauest. impairment plasma levels of ranitidine are increased and prolonged. Accordingly, in the presence of severe renal impairment clinicians may wish to reduce the dose by one half. References Children - Experience with Zantac Tablets in children is limited and such use has not been fully evaluated 1. Ireland etal: The Lancet, August 4, 1984; 274-275. 2. Barbara etal: International J. of Clinical Pharin clinical studies. It has however been used successfully in children aged 8-18 years in doses up to 150 mg twice daily without adverse effect. and Toxicology 1986; 24 (2): 104-107. 3. Product Monograph. 4. Silvis et al: J. of macology, Therapy and a!: of Interactions with other drugs - Although ranitidine has been reported to bind weakly to cytochrome (2:10-0. t ProdTheh Lancet, September 22, set198 oy 1985; 7)6):196; 42487 1984; 482-487. 5. Gough eta!: Clinical Gastroenterology P450 in vitro, recommended doses to the drug do not inhibit the action of the cytochrome P450-linked 8 659-662. 6. Simon etal: J. of Clinical Gastroenterology 1986; (3): 482-487. 7. Jensen etal: New oxygenase in the liver. There are conflicting reports in the literature about possible interactions between England Journal of Medicine 1983; 308: 883-887. 8. Data on File. 9. Smith etal: Br. J. of Clin Pharranitidine and several drugs, the clinical significance of these reports has not been substantiated. macology 1987; (23): 311-315. 10. Powell et al: Arch Internal Med 1984; (144): 484-486. Amongst the drugs studied were warfarin, diazepam, metoprolol and nifedipine. If high doses (2g) of sucralfate are co-administered with ranitidine the absorption of the latter may be 11. Sutherland etal: Eur J Clin Pharmacology 1987; 32: 159-164. 12. Siepler etal: Clin Pharmacy 1986 5 129-142. 13. Wormsley: Postgrad Med J 1988; 64 (Suppl 1): 47-53. hours. reduced. This effect is not seen if sucralfate is taken after an interval of 2 Adverse Reactions - Headache, sometimes severe, rash, dizziness, constipation, diarrhoea and nausea have been reported in a very small proportion of drug-treated patients but these also occurred in patients receiving placebo. A few patients on re-challenge with Zantac have had a recurrence of skin rash, headache or dizziness. Rare reports of bradycardia have occurred. Rare cases of reversible mental confusion and hallucinations have been reported, predominantly in severely ill and elderly patients. There have been a few reports of reversible blurred vision suggestive of a change in accommodation. Some increases in serum transaminases and gamma-glutamyl transpeptidase have been reported which have returned to normal either on continued treatment or on stopping Zantac. In placebo controlled studies involving nearly 2,500 patients, there was no difference between the incidence of elevations of SGOT and/or SGPT values in the Zantac treated or placebo treated groups. There have been occasional reports of reversible hepatitis (hepatocellular, hepatocanicular or mixed) with or without jaundice. Hypersensitivity reactions (urticaria, angioneurotic oedema, bronchospasm, hypotension) have been seen rarely following the parenteral and oral administration of Zantacg These reactions have occasionally occurred after a single dose. Reversible blood count changes (leucopaenia, thrombocytopaenia) have occurred in a few patients. Rare cases of agranulocytosis or of pancytopaenia sometimes with marrow hypoplasia have been PAAB Other haematological and renal laboratory tests have not revealed any drug related abnormalities. G CCPP Glaxo Canada Inc. No clinically significant interference with endocrine or gonadal function has been reported. There have
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