A number of retrospective studies have examined the incidence of CDAD in adult patients with IBD (summarized in ). While different parameters have been measured in each study, it is clear that adults with IBD have between two and three times higher incidence of CDAD than the adults without IBD. In the general pediatric population, one multi-center study (9
) found the incidence of CDAD in children to be comparable to that of non-IBD adults. Using these historical data for context, the incidence of CDAD in pediatric patients with IBD in our retrospective study (7.2 %) exceeds the incidence in children without IBD by 18- to 100-fold (9
) and adults with IBD by 1.5-fold (4
). Our center is thought to care for the vast majority of pediatric patients with IBD in our area, so it is likely that we were able to identify all or nearly all of the episodes of CDAD through our retrospective database review. Thus our data give an approximate incidence based on a large and stable population of children with IBD, and is consistent with Pascarella et al. in Italy (8
) who showed a 24.7% incidence of CDAD in children with IBD admitted to the hospital for diarrhea and abdominal pain.
While two adult studies have documented increased incidence of CDAD in patients with ulcerative colitis (UC) compared to those with Crohn’s Disease (CD) (5
) we did not see a similar association. It is not known if this represents a real difference between pediatric and adult UC or if this is an artifact of the composition of our population which is typical of the distribution of CD in children (3:1, CD:UC). Issa and coworkers (4
) also found that the incidence of CDAD in adult IBD patients (higher in patients with CD) matched the distribution of their IBD Center population. Furthermore, Pascarella and coworkers showed that specific IBD type was also not associated with CDAD incidence in pediatric patients (8
An important aspect of the changing epidemiology of CDAD is the increase in community-acquired cases (2
). This is particularly true for IBD patients. Similar to both adult and pediatric IBD patients (4
), the majority of CDAD in our pediatric patient population was community acquired. The increased number of community acquired infections among those with IBD has important surveillance implications and dictates even non-hospitalized patients are at risk for CDAD.
Symptoms of diarrhea and abdominal pain are common to both infectious colitis and to progression of IBD, and may signal a need for more aggressive IBD therapy rather than antimicrobial treatment. It is known that there is a relatively high rate of carriage of C. difficile
in IBD patients. In a prospective study, C. difficile
was detected in stool cultures from 8% of IBD patients (in remission) compared to 1 % of healthy controls, none of whom experienced clinical symptoms during a 6-month follow-up (7
). Our use of retrospective data precludes knowledge of carrier status, and it is a possibility that C. difficile
positive patients in our study who underwent multiple rounds of antimicrobial treatment prior to symptom resolution were indeed carriers whose symptoms were due rather to IBD exacerbation. Notably, Issa and coworkers (4
) also reported initial anti-microbial treatment failure in 58% of adult patients with IBD, much higher than reported in the general population (1
). The role of C. difficile
carriage in subsequent CDAD or in relapse in IBD patients is an important issue and remains to be elucidated.
The benefit of screening for C. difficile
toxin in IBD patients with apparent relapse is therefore controversial. However, in 2 recent studies of adult IBD patients during a relapse, from 5.5% – 19% of stool samples were found to be C. difficile
toxin positive, and these patients improved clinically after antimicrobial treatment (11
). Likewise, in another study, 25% of pediatric IBD patients admitted to the hospital had C. difficile
positive stool samples (8
). In the absence of a comprehensive prospective study, we would recommend C. difficile
toxin stool screening in all children with IBD experiencing an increase in disease symptoms in order to begin antimicrobial intervention in a timely fashion, with the caveat that failure may signal worsening of the underlying IBD.
Studies in adults with IBD have found either an increased risk of CDAD (4
) or a worse outcome in patients (13
) on immunomodulator treatments. In addition, PPI use has been found to be independently associated with CDAD risk (2
). While our study design did not allow us to look directly at these questions, we did examine risk in the context of recurrence and did not find any association in our pediatric population. Pascarella et al. did not find a correlation between CDAD and IBD therapy or PPI use in pediatric patients as well (8
Of note, we found that use of a common IBD anti-inflammatory medication (aminosalicylates) was associated with an improved response to treatment in patients with CDAD using these medications compared with patients not using these medications (P= 0.02). The biological basis of this finding is not known. The inflammatory effects of toxins A and/or B are required for at least part of the pathogenicity of C. difficile
and it may be that the reduction in pro-inflammatory cytokines mediated by aminosalicyates (14
) may aid in symptom resolution in certain individuals.
Limitations of our study include the use of retrospective data from a single-center tertiary care center, the absence of a control group, and the potential for type II errors due to sample size. However, our work does confirm the changing epidemiology of C. difficile infection in a pediatric IBD population, including an increased incidence of CDAD acquired in the community and greatly reduced effectiveness of both metronidazole and vancomycin.
More must be understood about the unique epidemiology of CDAD in the IBD population, including the role of mucosal/immunological factors, before treatment strategies can be improved to yield better outcomes. To further our current understanding, prospective studies must be performed that include identification of C. difficile carrier status, consistent definitions of treatment success and recurrence, and exploration of alternative therapies such as the use of probiotics, toxin binders, new antimicrobials and monoclonal antibody therapy.