Gastric Acid–Suppressive Agents Linked to Clostridium difficile Diarrhea
Proton-pump inhibitors (PPIs) and H2-receptor agonists (H2RAs) are associated with increased risk for community-acquired Clostridium difficile–associated disease (CDAD), according to the results of 2 population-based, case-control studies reported in the December 21 issue of JAMA.
“Recent reports suggest an increasing occurrence and severity of C. difficile–associated disease,” write Sandra Dial, MD, MSc, from McGill University in Montreal, Quebec, and colleagues. “Gastric acidity constitutes a major defense mechanism against ingested pathogens, and loss of the normal stomach acidity has been associated with colonization of the normally sterile upper gastrointestinal tract.”
Using the U.K. General Practice Research Database (GPRD), the investigators conducted 2 population-based, case-control studies. In the first study, each of 1,672 cases of C. difficile recorded between 1994 and 2004 was matched to 10 controls, based on calendar time and the general practice. In the second study, those cases not hospitalized in the previous year and therefore defined as community acquired were matched on practice and age with controls also not hospitalized in the prior year. Primary endpoints were the incidence of C. difficile and risk associated with use of gastric acid–suppressive agents.
The incidence of C. difficile diagnosed by general practitioners (GPs) increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. With current use of PPIs, the adjusted rate ratio (RR) of CDAD was 2.9 (95% confidence interval [CI], 2.4 – 3.4). With H2RAs, the RR was 2.0 (95% CI, 1.6 – 2.7), and with nonsteroidal anti-inflammatory drugs, RR was 1.3 (95% CI, 1.2 – 1.5).
“The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C. difficile,” the authors write. “The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further.”
Study limitations include the possibility of unknown risk factors that may have biased or confounded the analysis and lack of data concerning chemotherapy.
This study should remind us that almost all drugs can cause unintended consequences. We should prescribe any drug cavalierly. I always ask what the benefits are – and what risks the patient will have.
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2 Responses to PPIs add risk for C Diff
medsleuth
December 21st, 2005 at 10:47 am
As one who has suffered the ravages of C. diff. and who posts frequently about C. diff. in the news, I appreciate your comments and the wise reminder about prescription medications.
NRathod
September 19th, 2007 at 8:52 pm
C. Diff is a amazing bug, its very adaptive and the new strains really take advance of high use of PPIs and the fecal-oral route