Yersinia enterocolitica

OVERVIEW: What every clinician needs to know

Pathogen name and classification

Yersinia enterocolitica – A Gram-negative coccobacillus in the family Enterobacteriaceae.

What is the best treatment?

Fluoroquinolones are the drugs of choice for Y. enterocolitica infections, based on clinical observations and in vitro antimicrobial resistance studies. Third generation cephalosporins, trimethoprim-sulfamethoxazole and aminoglycosides also appear to be clinically effective.
Penicillins (including ureidopenicillins), imipenem, and first and second generation cephalosporins should NOT be used for treatment. Clinical observations suggest that these agents are either ineffective clinically, or have minimal effectiveness. These observations correlate with findings in in vitro antimicrobial resistance studies.
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While testing of antimicrobial susceptibility is always advisable, particularly for more serious infections, there have not been major problems with development of resistance to antimicrobial agents to which the organism has traditionally been susceptible.

How do patients contract this infection, and how do I prevent spread to other patients?

Epidemiology

The microorganism is primarily acquired from food. It is widely distributed in the environment, and frequently colonizes/infects wild and domestic animals. Pigs, in particular, are commonly colonized with Y. enterocolitica, with some studies reporting isolation of the organism from up to 90% of pork tongues/tonsils after slaughter. In Europe, infection has been associated with feeding of raw pork to infants; in the United States, there is a strong association with eating undercooked “chitterlings”, or pig intestines. While pork predominates as the vehicle of transmission, outbreaks have been linked with a wide range of other food products, from chocolate milk to tofu, and bagged salad greens. In China, over a quarter of cases in children have been associated with contact with pets; it has been hypothesized that this is related to feeding of raw meat (including pork) to dogs and cats in the household.
Y. enterocolitia is a psychrotroph – it grows well at low temperatures, including refrigerator temperatures. Epidemiologically, this is reflected in the association of illness/outbreaks with foods that have been refrigerated, and the increased frequency of illness seen during colder months and in more temperate climates.
Incidence rates vary widely. In the European Union, Y. enterocolitica is the third most common bacterial foodborne pathogen, after Campylobacter and Salmonella. In Germany, incidence between 2001 and 2008 was 7.2 cases/100,000 population/year, with the rate increasing to 58/100,000 among children under five years of age. This may relate to high colonization rates among European pigs, as well as the culturally-accepted practice of feeding raw pork to infants. In the United States, the reported incidence rate in the general population is 0.9 cases/100,000 population/year. The incidence among black infants in Georgia between 1996 and 1999 was 207 cases/100,000 population/year, with infections peaking around Christmas; feeding of chitterlings to infants during the holiday period has been implicated as the cause of these high rates. Infection with Y. enterocolitica is extremely rare in Bangladesh, a warm, Muslim country where dietary restrictions limit pork consumption.

Infection control issues

Y. enterocolitica is almost always foodborne; nosocomial transmission has not been noted as a significant problem. However, to minimize any possible risk, hospitalized patients with active Y. enterocolitica diarrhea or cutaneous infections should be placed under contact precautions.
Transmission of Y. enterocolitica through blood products does occur. Experimentally, Y. enterocolitica is able to grow in refrigerated blood products; it is hypothesized that initial contamination results from transient bacteremia in donors with Y. enterocolitica diarrhea (or who are convalescing from Y. enterocolitia diarrhea), with the organism then multiplying during refrigerated storage.
No vaccination is available or recommended. Prevention is based on avoidance of the microorganism by avoiding high risk foods such as raw pork and undercooked chitterlings; by thorough cooking of pork products; and by not feeding raw pork to pets.

What host factors protect against this infection?

Illness is most common among children under the age of 3, and in the elderly. It is unclear whether the link with children reflects differences in age-related susceptibility, versus pork feeding practices and/or pet contact. Among the elderly, infection, particularly invasive infection, tends to be more common among persons with chronic, underlying and/or immunosuppressive diseases.
Risk of invasive disease is increased among persons with conditions that predispose to iron overload, and/or persons on therapy with deferoxamine.
Infection is more common among persons with reduced gastric acidity, presumably due to loss of the gastric acid barrier.
Among persons who are HLAB27-positive, there is a greatly increased risk of post-infectious complications, particularly reactive arthritis.

What are the clinical manifestations of infection with this organism?

Patients withY. enterocolitica infections present most commonly with diarrhea, accompanied by a low-grade fever (reported in 60-80% of patients) and abdominal pain. A quarter to a half of patients report gross blood in their stool. Nausea and vomiting occur, but are less common, affecting a quarter of patients.
A subset of patients (ca 10-20%) present with “pseudoappendicitis”. This clinical syndrome is characterized by fever, severe abdominal pain, tenderness of the right lower quadrant, and leukocytosis. While not prominent in the symptom complex, two thirds of patients will have a history of one or two days of mild diarrhea. Pseudoappendicitis is proportionately more common among older children and young adults, as compared with the more classic symptoms of gastroenteritis seen in young children. In one study in Ireland, it was estimated (based on serologic testing) that 4% of patients undergoing appendectomies actually had acute Y. enterocolitica infections. At the time of surgery, such patients tend to have enlarged mesenteric lymph nodes (mesenteric adenitis), with a normal or slightly inflamed appendix. Y. enterocolitica may be cultured from involved lymph nodes, as well as from the distal ileum.
Y. enterocolitica infection may also present with isolated extraintestinal manifestations. This may include pharyngitis (primarily seen in adults), cellulitis, wound infections, abscess formation, and suppurative lymphadenitis. In one study, Y. enterocolitica was isolated as an unanticipated finding from 2 of 368 pediatric lymph node biopsies.
In rare instances, patients will present with bacteremia and septic shock. This may be seen in patients with transfusion-associated infections, and/or who have significant underlying diseases resulting in immunosuppression or iron overload. The fatality rate among persons with transfusion-associated sepsis is over 50%.

What common complications are associated with infection with this pathogen?

Y. enterocolitica is a very common cause of reactive/post-infectious complications, particularly reactive arthritis and erythema nodosum. Reiters syndrome, myocarditis, glomerulonephritis, and autoimmune thyroid disorders have also been linked with infection. Reactive arthritis may last from 1 to 4 months, with long-term disability reported. Involved joints are culture negative, although microbial antigens have been identified in the synovial fluid. Eighty percent of patients with reactive arthritis have the HLA-B27 histocompatibility antigen; this association is not seen with erythema nodosum and other reactive complications. Interestingly, reports of reactive complications appear to be much more common in Scandinavia than in other areas; it is unclear whether this is related to host factors or pathogen characteristics.

How should I identify the organism?

Isolation of Y. enterocolitica from stool generally requires the use of specialized procedures. Recovery is facilitated by use of Cefsulodin-Irgasan-Novobiocin (CIN) selective agar; given the ability of the microorganism to grow in the cold, use of a cold enrichment step is also helpful. When Y. enterocolitica is suspected as a cause of diarrhea, the microbiology laboratory should be notified, so that appropriate isolation techniques can be used. Isolation from other sites does not require specialized media, as the organism grows well on blood and nutrient agar.
If possible, isolates should be serotyped and/or biotyped. Human illness is most commonly associated with Y. enterocolitica strains in serogroups O:3, O:5,27, O:8, and O:9; and biogroups 1B, 2, 3, and 4. Isolation of a strain outside of these serogroups/biogroups should raise questions about its potential pathogenicity.
Because of the need for specialized techniques for isolation from stool, recent efforts have been directed toward development of molecular approaches for identification of the microorganism. At an experimental level, such techniques are in common use. There are now commercial systems coming on line that can identify multiple enteric pathogens, including Y. enterocolitica, using genetic/molecular approaches; widespread adoption of such systems for screening of stool samples is likely to increase the rate at which Y. enterocolitica infections are diagnosed.
There is a long tradition, particularly in Europe, of using serologic testing to diagnose infection. While of clear value, interpretation of data is complicated by the cross-reactivity of Yersinia antigens with Brucella, Morganella, and some Salmonella and rickettsial species.

How does this organism cause disease?

Y. enterocolitica is an intracellular pathogen. It invades and survives within macrophages and may persist and grow within lymph nodes and other lymphoid tissue (in animals and in humans) for extended periods of time. Adherence, invasion, and survival in lymphoid tissue depend on a range of virulence factors encoded by the Y. enterocolitica chromosome or the 65-70 kb virulence plasmid (pYV): key factors needed for virulence include invasin, AIL (the attachment-invasion locus), and YadA (Yersinia adhesin A), as well as LPS. Y enterocolitica also produces a heat stable enterotoxin, YST, which may play a key role in causation of diarrheal disease.
As we are coming to recognize with other bacterial pathogens, changes in environmental and/or host conditions (including changes in temperature) can result in changes in gene expression profiles, with corresponding shifts in virulence.
Auto-immune/post-infectious complications appear to be mediated by cross-reactivity between Yersinia and host antigens. Identification of the specific antigens involved in this cross-reactivity remains an area of active investigation.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Evidence for antimicrobial effectiveness in treatment of Y. enterocolitica infections is based solely on observations reported as part of case series. As this evidence correlates with in vitro antimicrobial resistance testing, use of these case series-based recommendations appears reasonable. Final recommendations on therapy will require randomized controlled trials (which are currently not available).

Relevant literature

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