C difficile Infection Linked to Proton Pump Inhibitors

Larry Hand

July 24, 2013

In addition to reducing inappropriate antibiotic use and providing better infection control in outpatient settings, strategies to control Clostridium difficile infection (CDI) should include further examination of outpatient and household settings and a reduction in proton pump inhibitor (PPI) use, according to an article published in the July 22 issue of JAMA Internal Medicine.

Amit S. Chitnis, MD, MPH, from the National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues conducted a population- and laboratory-based study of CDI in 8 US states between January 1, 2009, and May 31, 2011. Although CDI traditionally has been associated with antibiotic use, advancing age, and prior hospitalization, in recent years, risk factors include younger age and community settings, the researchers write.

The researchers conducted interviews with 1101 patients and cultured stool samples from 388 of the interviewed patients.

Of 984 confirmed cases of community-associated CDI, 407 (41.4%) had a high-level healthcare exposure such as an emergency department visit, 400 (40.7%) had a low-level healthcare exposure, which included dental, physician, or other outpatient appointments, and 177 (18.0%) had no recent healthcare treatment.

The patients were a median age of 51 years, and most were women (66.6%) and white (86.3%). Nearly two thirds (64.1%) reported antibiotics use within 12 weeks of CDI, most commonly for ear, sinus, or upper respiratory tract infection. However, 273 (27.7%) patients reported recent PPI use, and PPI use was more common among patients who did not have antibiotics recently (31.2%) than it was among those who did (25.8; P = .07).

"We found that patients having community-associated CDI without antibiotic exposure had a trend toward having received PPIs more frequently than patients with antibiotic exposure," the researchers write. However, concentrating on those individuals would prevent only 11.2% of community-associated CDI.

"Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings," the researchers write, but additional strategies should include "further examination of C difficile transmission in outpatient and household settings and reduction of PPI use."

In an accompanying invited commentary, Kent A. Sepkowitz, MD, from the Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York City, writes, "[M]ost disturbingly, [PPI] is available over the counter, propped up by substantial direct-to-consumer advertising muscle.... [I]t is out there for anyone with a dollar and a stomach ache."

He concludes, "PPI use is surely associated with the development of C difficile-associated diarrhea, and less PPI use should lead to less disease."

This study was funded by the Emerging Infections Program Cooperative Agreement between study sites and the Centers for Disease Control and Prevention. The authors and the editorialist have disclosed no relevant financial relationships.

JAMA Intern Med. 2013;173:1359-1367, 1367-1368. Article abstract, Commentary extract

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