INTRODUCTION — Yersinia species are gram-negative coccobacilli, which are facultative anaerobes [1]. Three species of Yersinia produce human illness: Yersinia pestis (the causative agent of human plague), Yersinia enterocolitica (the causative agent of yersiniosis), and Yersinia pseudotuberculosis. Y. enterocolitica and Y. pseudotuberculosis most commonly cause enterocolitis; Y. enterocolitica is the more common of the two species to cause disease.
The treatment of Y. enterocolitica and Y. pseudotuberculosis infection will be reviewed here. The epidemiology, microbiology, pathogenesis, clinical manifestations, and diagnosis of these infections and issues related to plague are discussed separately. (See "Epidemiology, microbiology, and pathogenesis of Yersinia infections" and "Clinical manifestations and diagnosis of Yersinia infections" and "Epidemiology, microbiology and pathogenesis of plague (Yersinia pestis infection)" and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)
TREATMENT — Optimal treatment strategies for Yersinia spp infections are unclear. Although treatment appears not to impact mild intestinal disease, fecal shedding decreases following antimicrobial treatment [2]. This by itself does not justify treatment, as person-to-person transmission is rare. However, antimicrobial treatment may be lifesaving in invasive infections.
There has been one controlled trial of antimicrobial therapy for Y. enterocolitica infection and one for Y. pseudotuberculosis gastroenteritis [3,4]. Neither demonstrated a clinical benefit from treatment, though, in both treated groups, the pathogen was rapidly cleared from feces. In addition to these studies, treatment recommendations are based on susceptibility data and clinical case series.
In vitro studies — Yersinia susceptibilities vary with the serotype, and therapeutic decisions should be guided by the susceptibility pattern of the clinical isolate [1]. The Y. enterocolitica serotype most commonly associated with illness (O:3) usually produces chromosomally-mediated beta-lactamases and thus is resistant to penicillin, ampicillin, and most first generation cephalosporins [1,5]. Yersinia is also usually resistant to macrolides.
Clinically significant strains are usually susceptible to other beta-lactam agents, aminoglycosides, tetracyclines, chloramphenicol, trimethoprim-sulfamethoxazole, and fluoroquinolones [6]. In one series, strains were uniformly susceptible to piperacillin, imipenem, ceftazidime, cefepime, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole [7].
Fluoroquinolone resistance — Quinolone resistance, including resistance to nalidixic acid and reduced susceptibility to ciprofloxacin, has been documented in Spain, due to mutations in DNA gyrase and an efflux pump, which may limit the effectiveness of these agents [8,9]. As Y. enterocolitica rarely spreads from person to person, this resistance is more likely due to the use of antimicrobials in agriculture than in human medicine.
Enterocolitis — There are no controlled trials that indicate that antimicrobial treatment of acute, uncomplicated yersiniosis is beneficial. In a retrospective case series of Y. enterocolitica gastroenteritis from Norway (67 case-patients and 132 controls), treatment was not associated with a decreased duration of illness (18 versus 21 days) [2]. There also was no clinical benefit demonstrated in a small prospective, placebo-controlled trial of trimethoprim-sulfamethoxazole (10 mg/kg TMP and 50 mg/kg SMX per day in two divided doses) in 34 Canadian children [3]. The initiation of therapy was significantly delayed in both studies (>20 days after disease onset in Norway and 12 days in Canada), as the onset of yersiniosis is often insidious. It is unclear if earlier treatment would prove more beneficial. However, rapid microbiologic clearance of the organism was observed following treatment in both of these studies.
There was no clinical benefit from ampicillin treatment in a prospective placebo-controlled trial in 136 pediatric patients with Y. pseudotuberculosis infections in Japan [4]. Although there was no difference in clinical response between treatment and control groups, following five days of treatment, clearance of the organism was significantly greater in the ampicillin group (continued organism excretion 0 versus 90 percent, respectively). There is also no evidence that early antimicrobial therapy reduces the frequency or severity of chronic sequelae for either Y. enterocolitica or Y. pseudotuberculosis [10,11].
Most cases of Yersinia enterocolitis do not merit treatment and no clinical benefit of treatment has been documented. Bearing in mind the lack of clinical efficacy data, should treatment of an individual case be judged clinically necessary because of clinical severity or underlying condition of the patient (eg, immunocompromised patients), we suggest a fluoroquinolone such as ciprofloxacin (500 mg twice daily) or trimethoprim-sulfamethoxazole for the pediatric patient (TMP 8 mg/kg per day and SMX 40 mg/kg per day in two divided doses).
We suggest doxycycline or trimethoprim-sulfamethoxazole as alternatives to fluoroquinolones for complicated gastrointestinal infections or focal extraintestinal infections [12].
Septicemia — Antibiotics are indicated for the treatment of complicated illness such as septicemia [12]. Mortality associated with Yersinia bacteremia has decreased from 30 percent in the 1970s to less than 10 percent in the late 1980s, presumably as a result of improved therapy [13].
In a retrospective case series of 43 patients with Y. enterocolitica septicemia, third generation cephalosporins with or without other antibiotics were effective in 85 percent of cases; fluoroquinolones alone or in combination, cured all of 15 infections [14]. Ampicillin, amoxicillin, first-generation cephalosporins, and amoxicillin-clavulanate when used alone were not effective. The duration of therapy varied from two to six weeks, with a median of 22 days (intravenous followed by oral therapy).
In patients with septicemia or severe disease, we recommend intravenous therapy with a third generation cephalosporin such as ceftriaxone (2 g per day in adults or 100 mg/kg per day in one or two divided doses in children, to a maximum dose of 4 g per day) combined with gentamicin (5 mg/kg per day in one to three divided doses). An alternative antibiotic to replace ceftriaxone is ciprofloxacin, if susceptible.
Duration of treatment — There have been no controlled trials examining the duration of antimicrobial therapy in Yersinia spp infections. Treatment recommendations are based on clinical case series. We suggest that if enterocolitis is treated, patients should receive five days of oral antibiotics. We suggest that more severe extraintestinal infections, including septicemia, receive three weeks of therapy; the patient can be switched to oral agents, once clinically improved, to complete therapy [14,15].
PREVENTION — Measures to prevent Yersinia infection include safe food processing and preparation and hand washing after exposure to pigs or raw pork products, as well as avoiding consumption of raw pork.
Food safety — The food industry plays a critical role in preventing yersiniosis. Reducing levels of contamination of raw pork products with Yersinia by improved hygiene at slaughter is important. Pasteurizing milk and maintaining high standards of sanitation in dairy plants prevents contamination of dairy products.
The most common food vehicles implicated in Y. enterocolitica infection transmission are pork and raw pork products, particularly tripe or chitterlings. A common route of transmission is indirect, via the hands of the person handling the raw food to the formula bottle of the infant. Separating the two tasks of preparing raw meat foods and caring for an infant is an important prevention measure.
Careful washing of hands, cutting boards and utensils with soap immediately after handling raw meats, as well as general measures to prevent cross contamination in the kitchen can help prevent transmission. Persons preparing pork should avoid eating raw or undercooked pork, even as part of adjusting spices while cooking. Consumption of raw ground pork, common in some Northern European countries, is to be avoided [16].
In Finland, foodborne Y. pseudotuberculosis has most often been associated with carrots and lettuce, possibly contaminated in the field or during winter storage by wild animals carrying the pathogen [17]. Protected harvest and safe storage of winter vegetables may help reduce such infections.
Animal exposure — Handwashing and the control of environmental cross-contamination are important measures to prevent zoonotic transmission of yersiniosis. Pigs are a natural reservoir for Yersinia spp and thus, particular care after handling these animals is warranted. (See "Epidemiology, microbiology, and pathogenesis of Yersinia infections".)
Waterborne transmission — Waterborne transmission is prevented by routine municipal water treatment and disinfection.
Transfusion-transmitted — Testing units of packed red blood cells for the presence of bacterial endotoxin, and limiting the shelf-life of packed red cells may be helpful in preventing transfusion-associated sepsis [18]. (See "Transfusion-transmitted bacterial infection".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
SUMMARY AND RECOMMENDATIONS
●Three species of Yersinia produce human illness: Yersinia pestis (the causative agent of human plague), Yersinia enterocolitica, and Yersinia pseudotuberculosis. Y. enterocolitica and Y. pseudotuberculosis most commonly cause enterocolitis (yersiniosis). (See 'Introduction' above.)
●There are no controlled trials that indicate that antimicrobial treatment of acute, uncomplicated yersiniosis is beneficial. We suggest not treating enterocolitis with antibiotics unless the patient has severe disease or has an underlying comorbid illness. (Grade 2B). (See 'Enterocolitis' above.)
●If enterocolitis requires treatment, we suggest treatment with a fluoroquinolone in adults (eg, ciprofloxacin 500 mg twice daily) or trimethoprim-sulfamethoxazole in children (TMP 8 mg/kg per day and SMX 40 mg/kg per day in two divided doses). (Grade 2C). We typically treat with antibiotics for five days. (See 'Enterocolitis' above.)
●We recommend intravenous therapy for patients with septicemia or severe disease (Grade 1B). The preferred regimen is a third generation cephalosporin such as ceftriaxone (2 g per day in adults or 100 mg/kg per day in one or two divided doses in children, to a maximum dose of 4 g per day) combined with gentamicin (5 mg/kg per day in one to three divided doses). Ciprofloxacin (500 mg twice daily) can be used in place of ceftriaxone in adults if the isolate is susceptible. The typical duration of treatment is three weeks. (See 'Septicemia' above.)
●Measures to prevent Yersinia infection include safe food processing and preparation and hand washing after exposure to pigs or pork products. (See 'Prevention' above.)
