Exposure to Acid Suppression Therapy Linked to C. difficile Infection in Children



PHILADELPHIA, PA—Children treated with gastric acid suppression therapy—particularly, proton pump inhibitors (PPIs)—had significantly higher healthcare- and community-associated Clostridium difficile infection, investigators reported at IDWeek 2014.

These findings are “likely due to the fact that gastric acidity is a major defense mechanism against ingested pathogens,” noted Stephen Eppes, MD, of Christiana Care Health System, Newark, DE, and colleagues.

The study, to the investigators' knowledge the largest to date of risk factors for pediatric C. difficile infection, recommends that for each patient, practitioners should always weigh risks versus benefits before prescribing gastric acid suppression. Over the past decade, prescription of gastric acid suppression therapy in children has increased, as has incidence of C. difficile infection. In adults, this therapy has been linked to community-acquired pneumonia and gastroenteritis as well as C. difficile infection.

Between 2005 and 2010, the investigators conducted a retrospective case-control study at Nemours/Alfred I. duPont Hospital for Children, a 200-bed academic pediatric hospital and associated outpatient clinics. Cases were defined as children ages 1–18 years with a first positive test for C. difficile toxin A/B on liquid stool. Each case was matched to 2 controls without C. difficile.

Selected comorbidities and exposure to gastric acid-suppression therapy, including histamine 2 receptor antagonists and PPIs, as well as antibiotics in the 3 months preceding the infection or encounter date were determined by chart review.

A total of 138 children with C. difficile infection was identified, 61% community-associated and the remainder healthcare-related or indeterminate, and 276 controls. Use of any acid suppression therapy was more common in cases, 34%, compared with 20% of the controls (P<0.01).

“When adjusted for demographic variables and comorbidities, gastric acid-suppression therapy remained significantly associated with C. difficile infection,” they reported, with an adjusted odds ratio (aOR) of 1.76 (95% confidence interval [CI] 1.01–3.10; P=0.05). In their adjusted model, antibiotic use (aOR 1.73; 95% CI 1.10–2.70) and immunosuppressed state (aOR 2.5; 95% CI 1.2–5.2) were also associated with C. difficile infection.

They found an even stronger association between C. difficile infection and gastric acid suppression among community-based cases, aOR 2.92 (95% CI 1.2–7.0) and antibiotic exposure, aOR 3.96 (95% CI 2.1–7.6). In addition, when analyzed as continuous variables, younger age increased the odds of C. difficile infection. Since “younger children have 50% less hydrochloric acid production than adults,” they hypothesized, “colonization probably contributed to this observation.”

“Larger pediatric studies are necessary to determine the role of PPIs specifically in causing C. difficile infection in children,” Dr. Eppes concluded.

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