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CLOSTRIDIUM DIFFICILE RIBOTYPE 027–ASSOCIATED DISEASE IN CHILDREN WITH NOROVIRUS INFECTION

Lukkarinen, Heikki MD*; Eerola, Erkki MD; Ruohola, Aino MD*; Vainionpää, Raija PhD; Jalava, Jari PhD§; Kotila, Saara MSc; Ruuskanen, Olli MD*

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The Pediatric Infectious Disease Journal: September 2009 - Volume 28 - Issue 9 - p 847-848
doi: 10.1097/INF.0b013e31819d1cd9
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Abstract

The recent global emergence of the hypervirulent strain PCR ribotype 027 (North American pulsed-field type 1, NAP1) of Clostridium difficile is associated with increased morbidity and mortality of C. difficile–associated disease (CDAD) in adults.1C. difficile ribotype 027-induced CDAD is infrequently seen in healthy young children and development of CDAD has not been connected with simultaneous or preceding viral gastroenteritis. We report 2 cases of previously healthy children who developed C. difficile ribotype 027 diarrhea after norovirus gastroenteritis.

CASE 1

A previously healthy 3-year-old boy was admitted to the Turku University Hospital after a 6-day history of vomiting and diarrhea. All family members were experiencing similar symptoms. He had received amoxicillin treatment for acute otitis media a month before the onset of gastroenteritis. Rotavirus, adenovirus, and norovirus were examined from a stool sample by enzyme immunoassays (EIA in-house tests for rota- and adenovirus; IDEIA Norovirus, Oxoid, Denmark). Norovirus-antigen was positive. Diarrhea improved in 10 days after the onset, but he developed abdominal pain and bloody stools. Another stool sample was collected 12 days after the onset of diarrhea and growth of toxin producing (VIDAS C. difficile toxin A&B, bioMérieux SA, France) C. difficile was detected from the bacterial culture. Further genotyping by PCR revealed the presence of binary toxin gene cdtB and the typical 18 bp deletion of tcdC-gene (multiplex PCR, in-house test), representing the ribotype 027 strain of C. difficile.1C. difficile 027 strain was confirmed by ribotyping. Two weeks after the onset of diarrhea he received a 10-day course of oral metronidazole (30 mg/kg/d), which alleviated the symptoms, but did not eradicate C. difficile. Four weeks after metronidazole-treatment, the boy was asymptomatic and C. difficile was no longer cultured from his stool.

CASE 2

A previously healthy 4-year-old girl was admitted to Turku University Hospital with a 4-week history of diarrhea. She had received azithromycin treatment for acute otitis media a week before the onset of diarrhea. At the time of admission, she had a history of 3 days of fever, occasional bloody stools, and diarrhea. A stool sample, collected on the day of admission, was analyzed for rotavirus, adenovirus and norovirus by enzyme immunoassays and PCR for norovirus (in-house test). Norovirus (genogroup 2) was found by PCR analysis. In the same stool sample, C. difficile toxin A and B were positive. Bacterial culture revealed C. difficile, which was confirmed to be ribotype 027 by PCR ribotyping. An oral course of metronidazole (30 mg/kg/d) for 10 days did not reduce the symptoms. The patient was subsequently treated with vancomycin (50 mg/kg/d) for 6 days. Vancomycin treatment alleviated the symptoms, but did not eliminate the C. difficile. Four months after the onset the patient was asymptomatic, but was still carrying C. difficile ribotype 027. At the time of admission, all family members were tested for norovirus and the parents were positive, but C. difficile ribotype 027 was found only from the patient and her asymptomatic 3-year-old sister who was negative for norovirus and had no history of antibiotic use.

DISCUSSION

Previously, CDAD was thought to be a nosocomial disease associated with advanced age and use of broad-spectrum antibiotics.2 Recent global outbreaks of a hypervirulent strain of C. difficile have raised the concern of the changing epidemiology of CDAD.2,3 CDAD is still rare in children, but the increasing occurrence of community-acquired CDAD is potentially concerning in pediatric populations.4,5 Outbreaks of C. difficile infection in daycare centers have been reported unassociated with the hypervirulent strain.6 Overall the risk factors for CDAD in children are similar to adults, but in pediatric patients CDAD is often seen without antibiotic therapy.5 However, similar to adults, antibiotic exposure can disrupt normal microflora and predispose to C. difficile infection in children. Coinfection with other bacterial pathogens has also been described in pediatric patients,7,8 but an association between viral gastroenteritis and toxin producing C. difficile infection has not been reported until recently.9 Our patients were from families who had norovirus infection. In case 2, the 3-year-old sister, who was negative for norovirus, did not develop symptoms even though she had heavy growth of C. difficile ribotype 027 in her stool. We hypothesize that norovirus may affect epithelial homeostasis of intestine and exacerbate the effects of toxins produced by C. difficile ribotype 027. This hypothesis is supported by a recent case report of a 76-year-old woman with concurrent norovirus and C. difficile infection and with a similar sequence of events to the cases reported here.10

REFERENCES

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Keywords:

Clostridium difficile; norovirus; children

© 2009 Lippincott Williams & Wilkins, Inc.