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CDI infections common in children following antibiotic treatment
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Most community-associated Clostridium difficile infections among children occur after recent use of antibiotics prescribed for other conditions, according to recent study findings published in Pediatrics.
“Improved antibiotic prescribing is critical to protect the health of our nation’s children,” CDC Director Thomas Frieden, MD, MPH, said in a press release. “When antibiotics are prescribed incorrectly, our children are needlessly put at risk for health problems including CDI and dangerous antibiotic-resistant infections.”
Thomas Frieden
Joyanna M. Wendt, MD, MPH, of the National Center for Emerging and Zoonotic Infectious Diseases at CDC, and colleagues evaluated 944 cases of CDI among 885 children between Jan. 1, 2010, to Dec. 31, 2011, to determine incidence, clinical presentation, and outcomes across different age groups.
In children aged 1 to 3 years, incidence decreased from 66.3 per 100,000 children to 113.8 per 100,000 children during the study period, but disease incidence increased for children aged 13 to 17 years, from 8.8 to 25.6 per 100,000 children. Seventy-one percent of the cases were community-associated, followed by 17% community-onset, health care facility-associated infections and 12% health care facility-onset infections.
Thirty-three percent of the cases had documented antibiotic use during the 14 days before C. difficile-positive stool collection. Out of 84% of cases, 73% had documented antibiotic use within 12 weeks before diarrhea onset. Eighty-seven percent of cases had an outpatient health care exposure within 12 weeks before diarrhea onset.
“We found that the highest burden of pediatric CDI is in the community,” the researchers wrote. “Children from 12 to 23 months of age are at the highest risk of infection; and clinical presentation, disease severity, and outcomes are similar across all ages, supporting a pathogenic role of C. difficile among symptomatic young children. Exposure to antibiotics was very common, indicating the need for prevention efforts that focus on antibiotic stewardship in pediatric outpatients health care settings. Future studies will be important to identify potential sources of C. difficile acquisition among children in the community.”
The President’s Fiscal Year 2015 budget addresses the issue and requests funding for the CDC to “improve outpatient antibiotic prescribing practices and protect patients from infections, such as those caused by CDI.” The initiative would decrease outpatient prescribing by up to 20% and health care-associated CDI by 50% in 5 years. More than $2 billion in health care costs, 20,000 lives, and 150,000 hospitalization could be prevented with the 50% reduction, according to a CDC press release.
“As both a doctor and a mom, I know how difficult it is to see your child suffer with something like an ear infection,” Lauri Hicks, DO, director of CDC’s Get Smart: Know When Antibiotics Work program, said in a press release. “Antibiotics aren’t always the answer. I urge parents to work with their child’s doctor to find the best treatment for illness, which may just be providing symptom relief.”
Disclosure: The study was funded in part by the CDC. One researcher reports financial ties with Acetelion, Cubust, Merck, Novartis, Rebiotix, Roche, Summit, Sanofi Pasteur, and Viropharma.
Perspective
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Andi Shane, MD, MPH, MSc
Researchers from the CDC, University of Rochester Medical Center, Tennessee Department of Health, Minnesota Department of Health, University of California at San Francisco, Colorado Department of Health, Connecticut Emerging Infections Program, Emory University School of Medicine, Maryland Department of Health, New Mexico Department of Health, Oregon Department of Health, Stritch School of Medicine in Chicago and the Edward Hines Veteran’s Affairs Hospital in Hines, Illinois utilized active population-based and laboratory-based surveillance in their catchment areas to describe the epidemiology of Clostridium difficile in children three years of age and younger. Almost three quarters of cases were classified as community-acquired with the highest incidence of cases among white infants between 12 to 23 months of age. Recurrent disease occurred in 100 (11%) and 76 (8%) of the cohort had severe disease.
Underlying gastrointestinal conditions, including inflammatory bowel disease, were noted in older children as were inpatient collections and hospitalizations within seven days among those older children with outpatient stool collections. In concordance with other population based-studies of persons with CDI, almost three-quarters of cases were symptomatic with diarrhea and the same proportion had a history of receipt of an antibiotic in the 12 weeks preceding stool specimen collection. In contrast to adult studies, fluroquinolones and gastric acid suppressorss were not identified as having associations with infection, probably because this class of antimicrobials and these gastrointestinal agents are not routinely used in children. Despite the almost twofold higher incidence of infection among 13 to 23 month olds than 2 to 3 year olds and the fourfold higher incidence compared to 4 to 17 year olds, the burden of disease appeared equivalent among all age groups. The authors suggest that the higher incidence of disease in 13 to 23 month olds may be attributed to the correspondingly higher rates of antimicrobial receipt in this younger age group. Of note, 28% of C. difficile positive stools were obtained from children who reportedly had formed stools.
The attribution of C. difficile as the etiology of diarrhea when enzyme immunoassay or nucleic acid amplification tests detect toxin is challenging for clinicians. While toxin detection represents activity of C.difficile, the detection of toxin may be the “canary in the mine” that the host is experiencing gut dysbiosis. This may be a consequence of preceding antimicrobial use, a concomitant infection, or underlying gastrointestinal pathology. While this large population-based assessment supports similar burdens of disease across various pediatric age groups, the implication of CDI as the etiology of gastrointestinal symptoms may not consider the fact that toxin detection is the result of a number of factors that predispose the host to C. difficile activity. Furthermore, the isolation of toxin from formed stools suggests that asymptomatic shedding is observed. The optimal treatment for CDI is the withdrawal of the implicated antimicrobial(s) resulting in the restoration of gut flora. The addition of oral metronidazole or vancomycin, or other agents is designed to suppress the toxin producing activity of C. difficile while aiding in the restoration of the individual’s flora. Additional modalities including probiotic supplementation may assist with the replacement of active toxin producing C. difficle with beneficial microbes.
These results provide much needed population based data that aids in the understanding of pediatric C. difficile epidemiology. The prevention of dysbiosis through judicious use of antimicrobials, control of underlying gastrointestinal conditions, and optimizing nutrition, will likely reduce the notable burden of pediatric disease.
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