Invasive Infections Caused by Yersinia Enterocolitica in Infants

Yersinia species are important enteric pathogens. At present 11 species are recognized within the Yersinia genus, but only 3 species (Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica) are universally recognized as human pathogens.1 These organisms collectively cause a variety of intestinal and extraintestinal diseases ranging from gastroenteritis to zoonotic infections such as plague.1-3 Y. enterocolitica is the most frequently isolated species from human specimens and is responsible for almost all nonzoonotic human infections.2-7 Enteritis and enterocolitis are the most common presenting features in young children with the peak incidence occurring during the winter months and clusters around Thanksgiving and New Year's Day.3, 4, 8 Gastrointestinal infections are often associated with exposure to uncooked pork products such as intestines or to contaminated food, water or milk. Bacteremia is probably the most common manifestation of invasive disease caused by Y. enterocolitica. Yersinia sepsis is usually associated with underlying host risk factors. Many of the reported pediatric cases of Yersinia bacteremia have occurred in children with iron overload syndromes.9 The increased risk of invasive Yersinia infections in these patients is believed to be related to greater requirement of this microbe for iron.2, 9 In adults Yersinia bacteremia is usually associated with underlying conditions including liver disease, hemochromatosis, iron overload, malignancy, diabetes mellitus and AIDS.2, 3 We report two infants with invasive infection due to Y. enterocolitica, one with septic arthritis of the hip and the other with bacteremia and concomitant aseptic (presumed enteroviral) meningitis. Both infants were healthy, with no apparent risk factors that predisposed them to invasive infection caused by this organism. Both infections responded promptly to treatment with a broad spectrum cephalosporin. Case reports.Patient 1. RF, a 4-month-old black female, was admitted to Le Bonheur Children's Medical Center (LB-CMC) on December 5, 1994, with a history of fever and diarrhea for 2 days. One stool had been described as bloody. She lived in a rural area with her mother and three siblings. A diagnosis of ventricular-septal defect and atrial-septal defect had been made in the neonatal period, but she had received no cardiac or other medications. There was no animal exposure or history of blood transfusion. The family used well water. Physical examination revealed a febrile infant with a temperature of 39.5°C who was alert but irritable. The fontanel was soft. General physical examination was remarkable only for a systolic murmur consistent with a ventricularseptal defect. The peripheral white blood cell count was 18 100/mm3 with 33% polymorphonuclear neutrophils, 21% band forms and 27% lymphocytes. Hemoglobin was 8.8 mg/dl. Cerebrospinal fluid (CSF) revealed a white blood cell count of 122/mm3 with 18% polymorphonuclear neutrophils, 1% band forms, 24% lymphocytes and 57% monocytes and 2 red blood cells. The CSF glucose was 68 mg/dl (serum glucose 108 mg/dl) and CSF protein was 47 mg/dl. A Gram-stained smear of the CSF was negative for bacteria, and the bacterial culture was sterile. Blood culture grew Y. enterocolitica susceptible in vitro to cefotaxime, trimethoprim-sulfamethoxazole and aminoglycosides but resistant to ampicillin. Stool culture was negative for Yersinia or other enteric pathogens. Stool viral culture grew an enterovirus. No CSF viral culture was performed. The patient was treated with intravenous ceftriaxone and improved rapidly. A repeat blood culture was sterile and the patient was discharged home after completing 10 days of parenteral antibiotic therapy with the diagnoses of Yersinia bacteremia and probable enteroviral meningitis. The mother later recalled that the family had eaten chitterlings at Thanksgiving and that the infant had contact with family members who had prepared the meal. Case 2. CM, a 1-year-old white male infant, was admitted to Le Bonheur Children's Medical Center (LBCMC) on December 13, 1994, with a history of a febrile illness for ∼1 month. He had an initial episode of diarrhea and was treated with an oral antibiotic for 1 week. The diarrhea improved but he remained febrile; he was then admitted to a hospital and treated with intravenous antibiotics for an additional 10 days. At that time he refused to bear weight on his left leg. A technetium bone scan was reportedly negative, but he continued to have low grade fever and refused to bear weight on the left leg. He was then referred to LBCMC for additional evaluation. Initial physical examination at LBCMC revealed a febrile infant with a temperature of 38.5°C. The left hip was held in a flexed and abducted position, and there was pain with movement and decreased range of motion of that hip. Laboratory findings included a peripheral white blood cell count of 17 000/mm3 with 29% polymorphonuclear neutrophils and 56% lymphocytes. A technetium scan revealed increased uptake in the left hip joint and the adjacent lateral femoral epiphysis and metaphysis, suggesting septic arthritis and osteomyelitis. The blood culture was sterile. A Gram-stained smear of joint fluid aspirated from the left hip was negative, but the culture grew Y. enterocolitica which was susceptible in vitro to cefotaxime, trimethoprim-sulfamethoxazole, ampicillin and aminoglycosides. Incision and drainage of the left hip joint were performed the next day, and that culture also grew Y. enterocolitica. A stool culture was negative for Yersinia and other enteric pathogens. The patient was initially treated with cefuroxime and gentamicin. Two days after admission those antibiotics were discontinued and intravenous ceftriaxone was begun. The patient was treated for 2 weeks with intravenous ceftriaxone followed by 2 weeks of treatment with oral trimethoprim-sulfamethoxazole. He was asymptomatic and had normal range of motion and function of the left hip on follow-up 1 month later. No risk factors for Yersinia infection were discovered, and this infection was unrelated to that of Patient 1. Discussion. Infections caused by Y. enterocolitica have been increasingly reported in recent years.1, 8 At LBCMC, a 225-bed children's hospital that serves as a pediatric referral center for Memphis and the Mid-South area, Y. enterocolitica has been isolated from ∼10 to 20 stool specimens per year during the past 3 years. In a retrospective review Naqvi et al.7 found that the incidence of Yersinia enteritis was as frequent as enteritis caused by Campylobacter in the St. Louis area. Yersinia enteritis occurred more frequently during the winter months. Thirty-five percent of their patients were 3 months of age or younger, and Yersinia bacteremia was noted in 28% of them. In their study 12 patients had lumbar punctures performed; 2 had CSF pleocytosis with negative bacterial stains and cultures and both patients grew enteroviruses from stool specimens. Patient 1 in our report also had dual infection with Yersinia and an enterovirus; it seems likely that the aseptic meningitis was caused by the enterovirus. Yersinia septicemia in adults is associated with high mortality. Conversely in children the treatment of Yersinia bacteremia has generally been successful. In June and July of 1982 a large outbreak of Y. enterocolitica infection (172 culture-proved cases) occurred in Tennessee, Arkansas and Mississippi.10 Children appeared to be more likely than adults to contract Yersinia infection and accounted for most episodes of enteritis. However, extraintestinal infections occurred more frequently in adults during the outbreak. Of the 24 patients with extraintestinal infections caused by Y. enterocolitica, 14 had pharyngitis, 8 had bacteremia (1 of these patients also had meningitis), 2 had wound infections and 1 had a urinary tract infection. No cases of septic arthritis were identified. Pasteurized milk was implicated as the vehicle of transmission of Y. enterocolitica during that outbreak.10 A sterile, "reactive" arthritis is commonly associated with Yersinia enterocolitis infection (particularly in adults who are HLA-B27-positive), but pyogenic bone and joint infections caused by this organism are extremely uncommon, even among patients with bacteremia. Sinnott et al.11 reported a case of disseminated infection caused by Y. enterocolitica associated with vertebral osteomyelitis and empyema; the patient had no apparent predisposing factors for invasive yersiniosis. Thirumoorthi and Dajani12 reported a child with thalassemia major, liver cirrhosis and hemosiderosis who developed Y. enterocolitica osteomyelitis of the rib. Patient 2 presented with septic arthritis of the hip caused by Y. enterocolitica. To our knowledge this is the first reported case of osteoarticular infection caused by Y. enterocolitica in a child without predisposing risk factors. In a retrospective review of the therapy of invasive Y. enterocolitica infections associated with bacteremia, Gayraud et al.13 found that all human clinical isolates were susceptible to the broad spectrum cephalosporins and the aminoglycosides. The mortality rate in their review was 7.5%. The third generation cephalosporins effected clinical cure of invasive Yersinia disease in 85% of cases when used in combination with aminoglycosides. Fluoroquinolones alone or in combination cured all 15 adult patients and clinical improvement occurred rapidly. Both infants we treated responded promptly to therapy with cefuroxime or ceftriaxone. Both of our patients were younger than 1 year of age and neither had any apparent underlying host defense abnormality. The two infants presented to LBCMC ∼1 week apart in early to mid-December. The first patient was likely exposed to Yersinia by contact with a relative who had prepared pork intestines (chitterlings) for a Thanksgiving meal. The source of the Yersinia exposure for Patient 2 was not identified. Thus invasive Y. enterocolitica disease may occur in healthy infants and may include bacteremia and arthritis/osteomyelitis. Ibrahim AlMohsen, M.D. Gary Luedtke B. Keith English, M.D. Division of Infectious Diseases; Le Bonheur Children's Medical Center (IA, GL, BKE) Department of Pediatrics; University of Tennessee Memphis (IA, BKE) Department of Infectious Diseases; St.