AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Yersinia enterocolitica is an important human pathogen that researchers increasingly recognize as a cause of various clinical syndromes. In 1939, Schleifstein and Coleman first described the organism; however, it was not until the mid-1970s that improved stool culture techniques enabled its isolation.

Until 1976, only 61 cases of yersiniosis had been reported in the United States; however, within the last 30 years, understanding of the pathogenicity of the organism has increased significantly. In several countries, Y enterocolitica has eclipsed Shigella species and approaches Salmonella species and Campylobacter species as the cause of acute bacterial gastroenteritis. The pathogen most commonly affects young persons, but data are unclear as to whether this represents an increased susceptibility or a greater likelihood of developing symptomatic illness. Most cases are sporadic, but reports document large outbreaks centered on a single contaminated source.

Pathophysiology

Y enterocolitica is a gram-negative coccoid bacillus that demonstrates significant morphologic pleomorphism. This organism is a facultative anaerobe that is motile at 25°C and nonmotile at 37°C.

Y enterocolitica ferments glucose and is oxidase negative; most, but not all, isolates reduce nitrates. The presence of bile salts in the medium prevents the organism's ability to ferment lactose. Colonies of Y enterocolitica do not produce hydrogen sulfide in triple sugar iron medium, but they are urease positive.

Upon initial isolation on enteric media, Y enterocolitica resembles other common Enterobacteriaceae. Using duplicate sets of enteric media followed by incubation at both 25°C and 37°C for 48 hours increases the yield from stool cultures. Cefsulodin-irgasan-novobiocin (CIN) agar is highly selective for Y enterocolitica. It requires 18-20 hours of incubation at 25°C to create unique colony morphology. Y enterocolitica appears as 0.5- to 1.0-mm colonies with a red "bull's-eye" and a clear border. Use of this medium allows differentiation between Y enterocolitica and Y enterocolitica–like isolates.

Scientists classify the organism according to various distinct biochemical and serologic reactions. Researchers have developed 2 biotyping systems, 1 by Wauters and 1 by Nilehn, and have identified 34 serotypes and 5 biotypes. According to the Wauters system, most human strains are biotype 4, while fewer pathogenic strains may be biotypes 1 and 2. Scientists accomplish serotyping through bacterial agglutination of rabbit-O antisera. The serotypes that most clearly are pathogenic to humans include serotypes O:3, O:5, O:27, O:8, O:9, and O:13. Accurate identification of pathogenic strains requires consideration of both the biotype and the serotype because multiple cross-reacting O factors can occur in some strains.

Y enterocolitica, similar to other members of the genus Yersinia, is an invasive organism that appears to cause disease by tissue destruction. Researchers have elucidated several potential pathogenic properties. These properties include chromosomally mediated effects (eg, attachment to tissue culture, production of enterotoxin) and plasmid-mediated mechanisms (eg, production of Vw antigens, calcium dependency for growth, autoagglutination). Invasion of human epithelial cells and penetration of the mucosa occurs in the ileum, followed by multiplication in Peyer patches. A 103-kd protein, known as invasin and determined by the inv gene, mediates bacterial invasion.

Drainage into the mesenteric lymph nodes can lead to systemic infection or mesenteric adenitis. The enterotoxin produced by Y enterocolitica is similar to the enterotoxin produced by the heat-stable Escherichia coli; however, it likely plays a minor role in causing disease because physicians observe diarrheal syndromes in the absence of enterotoxin production. In addition, the toxin does not appear to be produced at temperatures higher than 30°C. The plasmid-mediated outer membrane antigens are associated with bacterial resistance to opsonization and neutrophil phagocytosis.

One unique property of Y enterocolitica is its inability to chelate iron. Iron is an essential growth factor for most bacteria and is obtained through the production of chelators known as siderophores. Y enterocolitica does not produce siderophores but can utilize siderophores produced by other bacteria (eg, deferoxamine produced by Streptomyces pilosus). Iron overload substantially increases the pathogenicity of the organism, perhaps through attenuation of the bactericidal activity of the serum. Researchers observe differences in the iron requirements between different serotypes of the organism. This may explain, in part, the varying degrees of virulence of certain serotypes.

Frequency

United States

Researchers have isolated multiple serotypes from sporadic outbreaks; however, serotype O:8 has been reported most commonly. Most infections occur in the northern United States. The true prevalence rate of Y enterocolitica infection is not known, but several studies report a 2.8% frequency of isolation in symptomatic individuals, while asymptomatic individuals rarely harbor the bacteria.

International

Researchers have isolated Y enterocolitica from patients in many countries worldwide, but disease appears to favor cooler climates. Most isolates are reported from Canada and Europe, where O:3 and O:9 isolates predominate. The O:3 serotype is common in Japan. Isolation of the bacterium in developing countries is uncommon.

Mortality/Morbidity

• Most infected subjects are symptomatic; however, asymptomatic carriage may occur. Death is uncommon, but the presence of Y enterocolitica bacteremia is associated with a case fatality rate of 34-50%.
• Physicians report various manifestations, including enterocolitis, pseudoappendicitis, mesenteric adenitis, reactive arthritis, erythema nodosum, septicemia, pharyngitis, dermatitis, myocarditis, and glomerulonephritis.
• Iron is an essential growth factor for the organism, and iron overload (eg, chronic hemolysis, hereditary hemochromatosis) is associated with an increased risk of systemic disease. Use of deferoxamine also increases patient susceptibility to disease.

Race

No race predilection exists.

Sex

Infection occurs in equal numbers of men and women, although females appear more likely to develop erythema nodosum.

Age

Reports document illness most commonly in younger age groups. Clinical manifestations of infection exhibit some age-dependent predilections, with development of reactive arthritis and erythema nodosum occurring more commonly in older patients. Older patients with more debility are more likely to develop bacteremia than younger, healthier patients are.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Diarrhea
• • This is the most common clinical manifestation.
  • The usual presentation is characterized by diarrhea, low-grade fever, and abdominal pain lasting 1-3 weeks. Diarrhea may be bloody in severe cases.
  • Vomiting is present in approximately 40% of cases.
• Mesenteric adenitis, mesenteric ileitis, or acute pseudoappendicitis
• • These manifestations are characterized by fever, abdominal pain, tenderness of the right lower quadrant, and leukocytosis.
  • Nausea, vomiting, diarrhea, and aphthous ulcers of the mouth can occur.
  • Patients often undergo surgery for appendectomy. Several Scandinavian studies suggest a prevalence rate of 3.8-5.6% for infection with Y enterocolitica in patients with suspected appendicitis.
• Reactive arthritis
• • Most commonly reported in Scandinavia, polyarticular arthritis can occur after infection with Y enterocolitica.
  • The onset of joint symptoms typically occurs 1-2 weeks after gastrointestinal illness and occurs in approximately 2% of patients.
  • The large joints of the lower extremities are involved most commonly, and symptoms usually persist for 1-4 months, although reports document prolonged syndromes.
• Erythema nodosum manifests as painful raised red or purple lesions, primarily on the lower extremities.
• Septicemia
• • Physicians report septicemia most commonly in patients who have predisposing conditions, including alcoholism, diabetes mellitus, or an underlying immune defect.
  • Patients with iron overload conditions or patients who are undergoing treatment with deferoxamine also are at increased risk secondary to the effect of iron on the virulence of the bacteria.

Physical

Physical findings may mimic those observed in appendicitis but commonly are nondiagnostic. The presence of extraintestinal symptoms after a gastrointestinal illness may indicate the possibility of yersiniosis.

• Enterocolitis
• • Hematochezia is present in approximately 25% of cases; fecal leukocytes and red blood cells are a common microscopic feature.
  • While most cases are self-limited, physicians have reported serious complications, including diffuse colonic ulceration, perforation, peritonitis, and intussusception.
• Reactive arthritis: A strong association exists between the presence of the histocompatibility antigen HLA-B27 and reactive arthritis. Approximately 80% of affected patients demonstrate HLA-B27 positivity.
• Erythema nodosum: HLA-B27 status does not appear to be related to the development of erythema nodosum, but women are affected more commonly than men are, and adults are affected more commonly than children are.
• Septicemia: Physicians widely report bacteremic spread to extraintestinal sites. This spread results in hepatosplenic abscesses, endocarditis, pulmonary abscesses, meningitis, and mucocutaneous manifestations.

Causes

• Scientists have linked infection with Y enterocolitica to ingestion of contaminated foods, water, and milk. Contaminated foods include pork, tofu, and poultry.
• In addition, transmission may occur directly from dogs, cats, and swine.
• Evidence does not suggest a role for an airborne route of infection or for insect vectors in the transmission of this disease.
• Reports of person-to-person spread are conflicting and generally are not observed in large outbreaks.

DIFFERENTIALS

Section 4 of 11  

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• Follow-up
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Other Problems to be Considered

Ischemic bowel disease

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Stool samples tested for leukocytes usually will produce positive results, but Y enterocolitica is not distinguished from other invasive pathogens.
• Obtain stool samples for culture. When Y enterocolitica infection is suspected, instruct the microbiology laboratory to use CIN agar, which is a differential selective medium with increased yield for Y enterocolitica. When using conventional enteric media, MacConkey agar incubated at 25°C for 48 hours produces the best results.
• Serodiagnosis
• • Various methods make serodiagnosis possible; however, carefully interpret the serodiagnosis of Y enterocolitica without a positive result on stool culture. Cross-reactions can occur with other organisms, and a background seroprevalence rate among different populations may confuse the diagnosis by acting as a false-positive result.
  • Methods available include tube agglutination, enzyme-linked immunosorbent assays, and radioimmunoassays.
  • Agglutinin titers typically increase 1-2 weeks after infection and peak at 1:200. Antibodies persist for several years.

Imaging Studies

• Ultrasonography may be useful in delineating true appendicitis from pseudoappendicitis.

Procedures

• Colonoscopy: Findings can be variable and are relatively nonspecific. Typically, the cecum contains aphthoid lesions and the terminal ileum has small, round elevations and ulcers (Image 1). An exudate may be present. The left side of the colon typically is not affected, but case reports of left-sided colitis with serotype O:8 do exist.
• Joint aspiration: Synovial fluid contains 500-60,000 white cells per cubic millimeter, with a predominance of polymorphonuclear cells. Cultures are sterile. Testing synovial fluid for bacterial antigens may be of some use in difficult cases (Image 2).

Histologic Findings

Histologic findings are consistent with acute and chronic inflammation. Yersiniosis does not produce unique histologic findings.

TREATMENT

Section 6 of 11  

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Medical Care

• The value of antibiotic therapy in uncomplicated acute diarrhea is not established. Manage diarrhea with fluid and electrolyte replacement and antibiotic therapy.
• The treatment of mesenteric adenitis is symptomatic.
• Antibiotic treatment in patients with bacteremia with focal extraintestinal manifestations and in hosts with enterocolitis is advisable.

Surgical Care

• The patient may need surgical drainage of abscesses.
• The patient may undergo surgical exploration if appendicitis cannot be ruled out safely.
• The findings on laparotomy usually are mesenteric lymphadenitis and terminal ileitis, with a healthy appendix.

Consultations

The diagnosis and management of yersiniosis does not require specific consultations.

• Infectious disease or gastroenterology consultations may be useful.
• Rheumatology consultation may be helpful in cases manifesting with erythema nodosum or reactive arthritis.

Diet

No special diet is required.

Activity

• No activity restrictions are indicated.
• Stool samples from infected subjects should be handled carefully to avoid infecting others, and strict hygiene practices should be maintained.

MEDICATION

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Treatment usually is supportive and directed at maintaining euvolemia. Occasionally, antibiotics may be used.

Drug Category: Antibiotics

The value of antibiotic therapy in uncomplicated acute colitis and mesenteric adenitis is not established.

Antibiotic therapy may be required in patients with septicemia, with focal extraintestinal manifestations, and in patients with enterocolitis who are immunocompromised.

Drug Name	Sulfamethoxazole (SMZ) and trimethoprim (TMP) (Bactrim, Septra)
Description	Combination antibiotic. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Adult Dose	160 mg TMP/800 mg SMZ PO q12h for 3 d
Pediatric Dose	<2 months: Do not administer >2 months: 150 mg TMP/m2/d PO bid for 3 d
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly people; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Discontinue at first appearance of skin rash or signs of adverse reaction; discontinue at first signs of Stevens-Johnson syndrome; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in pregnancy, breastfeeding women, folate deficiency (eg, people with chronic alcoholism, elderly patients, patients receiving anticonvulsant therapy, patients with malabsorption syndrome); hemolysis may occur in G-6-PD deficient individuals; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin with gram-negative activity.
Adult Dose	1 g IV qd for 3 d
Pediatric Dose	>7 days: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Diarrhea has been reported with nearly every class of antibiotic and is common with ceftriaxone; associated with gallbladder sludge and cholecystitis; caution in allergy to penicillin

Drug Name	Ciprofloxacin (Cipro)
Description	Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms but no activity against anaerobes. Interferes with bacterial DNA gyrase and inhibits production of bacterial DNA.
Adult Dose	500 mg PO bid for 3 doses
Pediatric Dose	<18 years: Not recommended
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid use in children, pregnancy, and breastfeeding women; adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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Further Inpatient Care

• Admit patients if evidence of severe dehydration, malnourishment, or septicemia is present.
• Carefully monitor patients who are immunocompromised or patients with conditions that place them at risk for septicemia (eg, alcoholism, cirrhosis, iron overload syndromes, conditions that require deferoxamine therapy, diabetes, malnourishment), using a low threshold for admission and treatment with supportive measures and antibiotic therapy.

In/Out Patient Meds

• Physicians have used antibiotics with success for yersiniosis.
• Avoid antidiarrheal medications.

Deterrence/Prevention

• Instruct patients and at-risk individuals about appropriate hygiene methods and signs and symptoms of infection.
• Encourage public awareness of outbreaks and modes of transmission.

Complications

• Infection carries a low mortality rate, but patients with significant comorbidities are at risk of bacteremia, with a reported case fatality rate approaching 50%.
• Reactive arthritis can last 1-4 months.

Prognosis

• Yersiniosis usually is either self-limited or is responsive to therapy; however, reinfection is possible.
• Septicemia is rare but does have a substantial case fatality rate.

Patient Education

• Educate patients and individuals at risk of infection about appropriate hygiene methods and signs or symptoms of infection.
• Encourage public awareness of outbreaks, modes of transmission, and ways to prevent transmission.

MISCELLANEOUS

Section 9 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
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Medical/Legal Pitfalls

• Exercise caution in differentiating yersiniosis from inflammatory bowel disease, specifically Crohn disease. Perform stool cultures on selective enrichment of possible inflammatory bowel disease before initiating inflammatory bowel disease therapy.

Special Concerns

• Patients with conditions that place them at risk for Y enterocolitica septicemia (eg, elderly patients, patients who are chronically ill, patients with iron overload, patients with chronic hemolysis, patients on deferoxamine therapy, patients who are immunocompromised) should be monitored closely and admitted for antibiotic therapy at the first sign of disseminated disease.
• In the event of acute outbreaks, attempt to isolate contaminated persons who had contact with the patient.

MULTIMEDIA

Section 10 of 11  

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• Multimedia
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Media file 1:  Yersinia enterocolitis in a 45-year-old white woman who presented with chronic diarrhea.
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Media type:  Photo

Media file 2:  Gram stain of Yersinia enterocolitica.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
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• Differentials
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• References

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Article Last Updated: Jun 24, 2005