|Pediatric Risk Factors for Severe Clostridium Difficile Infection: Are Children Just Small Adults?|
|Reviewed by: Kari A. Simonsen, MD, University of Nebraska Medical Center|
The current study by Kim et al. seeks to better define the epidemiology of Clostridium difficile (CDI) in children from 2 US sites. They conducted a nested case-control study to identify risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 large children’s hospitals.
Recent changes in the epidemiology of CDI among adults have been well-described, however, the situation amongst pediatric-aged patients is not as clear. Much of the epidemiological shift has been attributed to the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain. Whether there exist similar epidemiological shifts in pediatric patients has not been as well characterized, although there have been studies describing increased incidence of CDI among hospitalized and community-dwelling children.
In the risk factor study the patients with severe CDI were considered cases and those with non-severe CDI were considered controls. In the outcomes study patients with severe CDI comprised the exposed population and the non-severe patients were considered unexposed.
The study definition of CDI was presence of diarrhea (≥3 liquid stools in 24 hrs) and positive stool C. difficile toxins A/B ELISA results with subsequent study laboratory confirmation using alternative modalities. Severe disease was defined by at least one clinical complication or presence of at least 2 or more of the following supplemental laboratory criteria: white blood cell count >15 x103 µL or <5 x103 µL, albumin <2.5g/dL, elevated creatinine, visible or microscopically detected blood in stool, or fever (≥38.5C).
Patients were enrolled from 2 sites (The Children’s Hospital of Philadelphia and Rainbow Babies and Children’s Hospital). 82 were eligible for study inclusion, of which 58.5% (n=48) were classified as having severe CDI. Increasing age and exposure to multiple (3) antibiotic classes in the 30 days before infection were found to be associated with risk of severe CDI. The median age in the severe group was 5.93 years compared to 1.83 years in the non-severe group. If infants <1yr were excluded from the analysis, only receiving 3 classes of antibiotics remained statistically significant for association with severe disease. All patients with malignancy within the data set (n=10) met criteria for severe CDI. Rates of relapse or treatment failure did not differ significantly between the severe and non-severe groups, and the overall relapse rate was 24.4%. The epidemic NAP1 strain was isolated from 9 patients (11%) but was not associated with severity, relapse or treatment failure.
Treatment chosen by the patient providers was recorded, and the majority were treated with a single antimicrobial (72%) of which metronidazole was the most common (88%), followed by combination metronidazole and oral vancomycin (12%), and vancomycin alone (4%). Only 5 patients with severe CDI were treated initially with oral vancomycin (although the study period predates the current treatment guidelines published by IDSA/SHEA), and ultimately pediatric patients had fewer complications that adults with 12% experiencing complications across the entire cohort.
The study was limited by the lack of an accepted definition for pediatric severe CDI, potential for lack of generalizability as patients were recruited from 2 large tertiary centers in the US and might not be reflective of community hospital or ambulatory settings. Inclusion of patients in the analysis <1yr is also potentially confounding as asymptomatic carriage is common in this age group, and may be difficult to discern particularly from nonsevere CDI using the case definition. Also, the study size was modest, and it may have been underpowered to detect small differences between the severe and nonsevere groups for the risk factors queried.
The study does add credence to the assertion that recent exposure to multiple antibiotic classes, underlying malignancy, and older age place children at increased risk for severe CDI; and also raises some potentially intriguing differences in children vs adults including the possibility that the NAP1 strain is not associated with disease severity, that metronidazole first line therapy may be appropriate for severe CDI, and that children are generally at lower risk for complications from CDI even with severe illness.
Kim J, Shaklee JF, Smathers S, Prasad P, Asti L, Zoltanski J, Dul M, Nerandzic M, Coffin SE, Toltzis P, Zaoutis T. Risk Factors and Outcomes Associated with Severe Clostridium difficile Infection in Children. Pediatr Infect Dis J. 2012; 31(2):134-8.
Available at: http://journals.lww.com/pidj/Abstract/2012/02000/Risk_Factors_and_Outcomes_Associated_With_Severe.7.aspx