Yersinia enterocolitica infection – 7 Interesting Facts

Synopsis

Key Points

  1. Yersinia enterocolitica infection can result in a spectrum of illness ranging from a self-limiting diarrheal illness to terminal ileitis, mesenteric lymphadenitis, and occasionally sepsis
  2. Postinfectious sequelae of reactive arthritis or erythema nodosum may occur in a small proportion of patients
  3. Yersinia enterocolitica infection is usually acquired by eating or handling contaminated food (most commonly raw or undercooked pork products) or by contact with infected animals (primarily pigs)
  4. Clinical presentation may include fever, diarrhea, vomiting, abdominal pain, hemorrhagic stool, and less commonly, pharyngitis; may mimic acute appendicitis
  5. Yersinia enterocolitica infection may be suspected on basis of clinical presentation; diagnosis is confirmed by isolation of Yersinia enterocolitica in stool specimen
  6. Most infections are self-limiting; antibiotic therapy is usually unnecessary and does not reduce risk of postinfectious complications
  7. Antibiotic therapy with oral ciprofloxacin or trimethoprim-sulfamethoxazole is indicated for treatment of severe enterocolitis and for immunosuppressed patients; ceftriaxone or IV ciprofloxacin is indicated for bacteremic patients

Pitfalls

  • Yersinia enterocolitica infection may be misdiagnosed as appendicitis because of the similar clinical presentation in older children and young adults

Terminology

Clinical Clarification

  • Yersinia enterocolitica infection, also known as acute yersiniosis, is an acute infection caused by Yersinia enterocolitica bacterium 1
  • Commonly causes acute febrile diarrhea; more severe disease may result in terminal ileitis and mesenteric lymphadenitis (pseudoappendicitis) 2
    • Acute infection is followed by extraintestinal sequelae (eg, reactive arthritis, erythema nodosum) in a minority of patients
  • Average annual incidence was 1 case per 100,000 persons in the United States in 2017 3

Diagnosis of Yersinia enterocolitica infection

Clinical Presentation

History

  • Symptoms typically occur 24 to 48 hours after ingestion of Yersinia enterocolitica and are similar in both adults and children 1 4
    • Diarrhea and fever are present in most cases 1
    • Abdominal pain is common in adults; more commonly localized to right lower quadrant in children 1 5
      • May mimic appendicitis in older children and adolescents 5
    • Nausea and/or vomiting occurs in less than one-half of patients 6
    • Hemorrhagic stool (more common in children than adults) 7
    • Sore throat is a presenting symptom in a minority of cases but is an important clue to the diagnosis 6
  • Late manifestations, which may occur days to weeks after onset of gastrointestinal symptoms, include arthralgia or painful erythematous lesions on legs and trunk (erythema nodosum) 2 8

Physical examination

  • Patient is usually febrile
  • Abdominal tenderness may be present
    • May localize to the right iliac fossa; may be mistaken for appendicitis
  • Exudative pharyngitis may be present 8
  • Signs of dehydration may be evident
  • Raised erythematous lesions on legs and trunk may be observed in patients with erythema nodosum 9
  • 1 or more joints may be warm, swollen, and tender in patients with reactive arthritis
  • Rarely, signs of disseminated infection/sepsis (eg, tachycardia, tachypnea, hypotension, abscesses involving skin or other organs) are present; usually in elderly or immunocompromised patients 10

Causes and Risk Factors of Yersinia enterocolitica infection

Causes

  • Eating or handling contaminated food, most commonly raw or undercooked pork products 1
  • Infection may also be transmitted by:
    • Consuming unpasteurized milk and cheese, contaminated drinking water, or other contaminated products (eg, tofu) 11
    • Contact with infected animals or animal carcasses 2
      • Pigs are the major reservoir for infection; also found in rodents, rabbits, sheep, cattle, horses, and dogs
    • Blood transfusion (rare cause of septicemia) 2

Risk factors and/or associations

Age
  • In the United States, highest incidence in children 12
    • 47% of cases occur in children younger than 5 years and 32% of cases involve infants younger than 1 year 12
    • Black and Asian children younger than 5 years have the highest incidence of infection 2
Genetics
  • Postinfectious reactive arthritis following acute yersiniosis is most common in patients with HLA-B27 2
Ethnicity/race
  • In the United States, highest incidence is reported in black (0.9 cases per 100,000) and Asian populations (0.7 cases per 100,000) 12
    • Incidence in white populations is 0.2 cases per 100,000 12
Other risk factors/associations
  • Eating undercooked or raw pork products
  • Exposure to farm animals (primarily pigs)
  • Iron overload (eg, hereditary hemochromatosis) 2
  • Infection is more common in Northern Europe (especially Scandinavia), Japan, and Canada 13
  • Infection is more common in temperate climates in the cooler months of the year 2
    • In the United States, among black populations infection is more common in winter; no seasonal variation is seen in other races 12

Diagnostic Procedures

Primary diagnostic tools

  • Suspect based on clinical presentation and epidemiologic risk factors for yersiniosis
  • Diagnosis is made by isolation of Yersinia enterocolitica from culture 8 11
    • Stool culture is primary means of diagnosis and should be obtained in patients with diarrhea that is persistent or severe, accompanied by severe abdominal pain, fever, or hemorrhagic stool, or that occurs in patients who are immunocompromised 11
    • In the setting of exudative pharyngitis, obtain a throat swab
    • If surgery is performed for suspected appendicitis, culture peritoneal fluid or tissue from mesenteric lymph nodes
    • Obtain blood cultures in patients with evidence of sepsis
  • Serologic tests have been used to diagnosis yersiniosis in Europe and Japan but are not routinely used in the United States 10 11
  • Culture independent methods are recommended at least as adjuncts to traditional isolation methods for adults, particularly when culture methods fail to isolate causative organism 14
    • Polymerase chain reaction testing on stool specimens can accurately and rapidly detect bacterial DNA 9 15
    • Polymerase chain reaction offers improved sensitivity compared with traditional isolation measures (eg, culture) 14
    • Current list of FDA licensed gastrointestinal pathogen singleplex and multiplex nucleic acid based detection tests is available 16

Laboratory

Differential Diagnosis

Most common

  • 1Appendicitis
    • Inflammation of the appendix characterized by abdominal pain localized to the right lower quadrant, fever, vomiting, and sometimes mild diarrhea 18
      • Classic pattern is abdominal pain that begins in periumbilical region and localizes to the right lower quadrant, with generalized or localized peritonism
    • May be difficult to exclude as presentation is often indistinguishable in older children and young adults 19
    • Ultrasonography and CT scan may help to establish or exclude the diagnosis
  • Other bacterial pathogens causing invasive diarrhea (Related: )Nontyphoidal salmonella infection
    • Major causes are salmonella (nontyphoid), Shiga toxin–producing and shigella (Related: Campylobacter infections)Campylobacter jejuni,Escherichia coli,20
    • All may be associated with watery diarrhea, fever, abdominal pain, and blood or mucus in stool; clinical features do not help differentiate specific pathogen
    • May be suspected on basis of epidemiologic risk factors
    • Diagnosis is confirmed by isolation of causative organism on stool culture
  • Inflammatory bowel disease (Related: ) 1Crohn disease
    • Ulcerative colitis2122
    • May be suspected in patients with symptoms persisting for several weeks
    • Diagnose based on endoscopy and biopsy findings

Treatment

Goals

  • Provide supportive care for self-limited illness
  • Promote antibiotic stewardship with judicious use of antibiotics only when indicated

Disposition

Admission criteria

  • Admit patients with severe dehydration or sepsis 4
  • Monitor for signs of disseminated infection and consider admission in patients at risk for sepsis, including elderly patients and those who are immunocompromised or who have iron overload

Treatment Options

Supportive care

  • Supportive therapy includes oral rehydration with a glucose-electrolyte solution; IV rehydration is indicated if patient is severely dehydrated 23
  • Antimotility agents (eg, loperamide)
    • May improve symptoms in adults and individuals with traveler’s diarrhea 14 24
    • Contraindicated in infants and children, elderly patients, and patients with fever, severe pain, or dysenteric stools 17 24
  • Probiotic use is controversial 25 26
    • May shorten duration and diminish stool frequency; optimum dose/regimen is not currently available 27
    • Routine use is not advocated for most adult and child populations 14 28
  • Use ondansetron for patients with significant nausea and vomiting 25
    • One dose in children administered in the emergency setting can prevent need for parenteral rehydration and hospitalization 29
    • Multiple dose therapy in children lacks proven efficacy and may lead to increase in diarrheal episodes 29
    • Most infections are self-limiting; antibiotic therapy is usually only necessary in moderate to severe cases and does not reduce risk of postinfectious complications 13

Drug therapy

  • Fluoroquinolones
    • Ciprofloxacin
      • Checking for local resistance patterns is recommended 30
      • For severe enterocolitis and immunosuppressed patients with enterocolitis
        • Ciprofloxacin Hydrochloride Oral tablet; Adults: 500 mg PO twice daily for 5 days. 30
      • For bacteremic patients
        • Ciprofloxacin Hydrochloride Oral tablet; Adults: 400 mg IV twice daily for up to 3 weeks in bacteremic patients. 30
  • Sulfonamides
    • Trimethoprim sulfamethoxazole
      • For severe enterocolitis and immunosuppressed patients with enterocolitis
        • Sulfamethoxazole, Trimethoprim; Adults, Adolescents, and Children: 8 mg/kg/day of trimethoprim component PO in 2 divided doses daily for 5 days. 30
  • Cephalosporins
    • Ceftriaxone (for bacteremic patients)
      • For severely ill patients, use in combination with gentamicin until susceptibility data are known
      • Ceftriaxone Sodium Solution for injection; Infants, Children, and Adolescents: 100 mg/kg/day IV/IM divided every 12 to 24 hours (Max: 2 to 4 g/day) recommended by AAP for severe infections; FDA-approved labeling recommends 50 to 75 mg/kg/day IV/IM divided every 12 hours (Max: 2 g/day) for serious infections.
      • Ceftriaxone Sodium Solution for injection; Adults: 1 to 2 g IV/IM every 12 to 24 hours (Max: 4 g/day) depending on severity of illness and causative organism. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy; generally treat 7 to 10 days depending upon patient response, site of infection, and pathogen(s). Deescalate when possible.
  • Aminoglycosides (for bacteremic patients)
    • Gentamicin
      • To be given in addition to ceftriaxone
      • Gentamicin Sulfate Solution for injection; Adults, Adolescents, and Children: 5 mg/kg IV once daily or up to 3 weeks in bacteremic patients. 30
  • 5-HT₃ receptor antagonist
    • Ondansetron
      • Ondansetron Hydrochloride Oral solution; Infants and Children 6 months and older weighing 8 to 15 kg: 2 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
      • Ondansetron Hydrochloride Oral solution; Children weighing 15 to 30 kg: 4 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
      • Ondansetron Hydrochloride Oral solution; Children and Adolescents weighing more than 30 kg: 6 to 8 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
      • Ondansetron Oral disintegrating tablet; Adults: 4 to 8 mg PO as a single dose.

Nondrug and supportive care

Rehydration with fluid and electrolyte replacement 31

  • Balanced electrolyte solutions (ie, sodium of 60-75 mEq/L and glucose of 75-90 mmol/L) are preferred in 14 28
    • Infants and young children 28
    • Elderly with severe diarrhea 14
    • Individuals with voluminous, cholera-like watery diarrhea 14
  • Encourage commercially available oral rehydration solutions, which are effective in most patients
    • Oral rehydration therapy is contraindicated in 17
      • The initial management of severe dehydration
      • Children with paralytic ileus
      • Frequent and persistent vomiting (ie, more than four episodes per hour)
      • Painful oral conditions such as moderate to severe thrush (eg, oral candidiasis)
  • Amount of recommended oral rehydration therapy for mild to moderate dehydration in child
    • 50 to 100 mL/kg over 3 to 4 hours followed by additional replacement of ongoing losses (eg, 50-100 mL for each diarrheal stool or vomiting episode) 17
  • Recommend water, sports drinks, soups, and saltines in other adults with mild to moderate acute diarrhea 14
  • Nasogastric administration is an alternate effective route for enteral fluid administration in patients who do not tolerate oral fluids
    • May be most appropriate for malnourished or lethargic children but not feasible for otherwise healthy, active, older children 17
  • Administer IV fluid for patients with significant dehydration
    • Common indications for IV fluid include:
      • Continuing rapid stool loss
      • Frequent, severe vomiting
      • Insufficient intake of oral rehydration solution owing to fatigue or lethargy
      • Severe dehydration 17
    • Avoid hypotonic D5 1/4 NS replacement solution in patients with severe dehydration secondary to diarrheal disease 17
  • Encourage early refeeding with regular age appropriate diet to promote enteral recovery 24 28
    • Recommend frequent, small meals throughout the day; energy and micronutrient rich foods are ideal (eg, grains, eggs, meats, fruits, vegetables) 17
    • Avoid hyperosmolar canned fruit juices because they can aggravate diarrhea 17
    • Continue breastfeeding for nursing infants as tolerated 32
    • Avoid lactose during symptomatic diarrhea owing to risk of interval lactose intolerance with temporary lactase deficiency, particularly in infants and children 26 33
  • Standard infection control and contact precautions are required for all hospitalized patients

Comorbidities

  • Immunocompromised patients
    • Antibiotic therapy is indicated for treatment of severe or disseminated infections and infection in immunocompromised patients 11
  • Patients treated with desferrioxamine
    • Withhold desferrioxamine until illness resolves 10

Special populations

  • Children
    • Children with longer duration of diarrhea, moderate to severe dehydration, or atypical clinical presentation may require measurement of electrolytes and correction of dehydration or electrolyte abnormalities 17
    • Avoid empiric antibiotic treatment of bloody diarrhea in children younger than age 3 years until Escherichia coli 0157:H7 pathogen is excluded by stool culture, owing to increased risk of hemolytic uremic syndrome in this patient population
    • Fluoroquinolones are not approved for otherwise healthy children younger than age 18 years when alternate treatment is available

Complications and Prognosis

Complications

  • Postinfectious sequelae
    • Reactive arthritis 34
      • Reported in approximately 9% to 15% of cases 5 8
      • Manifests several days to 1 month after of onset of gastrointestinal symptoms and may persist for 1 to 4 months 8
      • Typically involves knees, ankles, toes, fingers, and wrists 8
    • Erythema nodosum
      • Reported in approximately 3% of cases (has been reported in up to 30% of cases in Scandinavia) 5 8
      • Painful erythematous lesions appear on the legs and trunk 2 to 20 days after onset of gastrointestinal symptoms and usually resolve within 1 month 8
    • Myocarditis 9
    • Glomerulonephritis 10
  • Extraintestinal complications (rare)
    • Septicemia
      • Increased risk in patients who are immunosuppressed or who have underlying conditions such as diabetes, alcoholism, malnutrition, or iron overload (eg, hereditary hemochromatosis, β-thalassemia, desferrioxamine therapy) 35
      • Rarely, transfusion-acquired 35
    • Metastatic infection following bacteremia 10
      • Abscesses in liver, kidney, spleen, or lungs
      • Pneumonia
      • Meningitis
      • Endocarditis, mycotic aneurysm
      • Osteomyelitis
      • Cutaneous infection (eg, cellulitis, bullae, pustules)

Prognosis

  • Acute gastrointestinal illness typically resolves within 1 to 3 weeks with no long-term sequelae in most patients 36
  • Hospitalization for severe disease is required in approximately 34% of patients 37
  • Mortality rate is very low; estimated annual mortality rate of 2% 37
    • Most deaths occur in patients older than 65 years 38

Screening and Prevention

Prevention

  • Patients should be given the following advice: 13
    • Avoid consuming raw and undercooked pork, unpasteurized milk or milk products, and untreated water
    • Wash hands before eating and preparing food, after contact with animals, and after handling raw meat (particularly pork)
    • Prevent cross-contamination in the kitchen
    • Dispose of animal feces in a sanitary manner
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