Pediatric C difficile Infection Linked to Common Prescription Drugs

Pediatric community-associated Clostridium difficile (C. difficile) infections are linked to medications regularly prescribed to children as well as exposure to outpatient clinic and family members with infections, according to a new report.

Researchers from the Uniformed Services University in Bethesda, Maryland, identified more than 1300 children with C. difficile between 2001 and 2013 to characterize the medication and other exposures linked to pediatric C. difficile infections. These patients were discovered using billing records from the US military health system database and the C. difficile infection diagnostic code from the International Classification of Diseases, Ninth Revision, Clinical Modification. The infected patients were between 1 and 18 years of age and were matched with almost 4000 healthy controls—3 healthy controls each.

The researchers then used the infected patients’ pharmacy records to pinpoint any medication exposures in the 12 weeks preceding their infection. The researchers included 10 classes of oral antibiotics in that category—including clindamycin, fluoroquinolones, sulfonamides, macrolides, penicillins, amoxicillin/clavulanate, tetracyclines, and first-, second-, and third-generation cephalosporins—2 gastric-acid suppression medications (proton pump inhibitors and H₂ receptor antagonists), and corticosteroids. The investigators also reviewed the patients’ healthcare exposure, and determined whether or not they had a sibling younger than 1 year of age or a family member with a C. difficile infection.

The majority of the children with C. difficile were prescribed at least 1 antibiotic in the 12 weeks leading up to their diagnosis (60%), the study authors reported. Of those children, 40% had been prescribed multiple classes of antibiotics: 31% with exposure to 2 classes, 9% of children with exposure to 3 or more classes of antibiotics. Fluoroquinolones, clindamycin, and third-generation cephalosporins were most commonly linked to pediatric C. difficile onset, the investigators found. The median time from antibiotic prescription to C. difficile diagnosis was 33 days.

The rate of developing C. difficile after antibiotic exposure was similar following exposure to proton pump inhibitors.

Visits to outpatient healthcare clinics also were linked to C. difficile infection, the researchers found, citing a 35% increase in the odds of infection development for each additional visit.

Contact with infected family members was associated with development of pediatric C. difficile infection, the study authors wrote. But, they said, exposure to a sibling under the age of 1 year was not linked to infection development.

Additionally, the researchers determined that pediatric C. difficile increased throughout the 12-year period of the study. The average annual increase reached 47.9%.

“Our study supports the occurrence of CDI among a population of children who were never hospitalized previously and provides a broad characterization of the medication and epidemiologic exposures associated with pediatric community associated C. difficile infection cases,” the study authors wrote.

“Improved stewardship of antibiotics is clearly important, but decreasing antibiotic exposure alone will not eliminate community associated C. difficile infection cases in children,” the authors concluded, adding that “judicious use of acid suppression medications highlight the need for efforts to better quantify C. difficile transmission and limit its spread both in ambulatory healthcare settings and in households.”

The study, titled “Risk Factors for Community-Associated Clostridium difficile Infection in Children,” was published in The Journal of Pediatrics.