Gastric Acid–Suppressive Agents Linked to Clostridium difficile Diarrhea

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Gastric Acid–Suppressive Agents Linked to Clostridium difficile Diarrhea CME

News Author: Laurie Barclay, MD

CME Author: Désirée Lie, MD, MSEd

Disclosures

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Release Date: December 20, 2005; Valid for credit through December 20, 2006

Credits Available

Physicians - up to 0.25 AMA PRA Category 1 continuing medical education credits

for physicians ;

Family Physicians - up to 0.25 AAFP Prescribed continuing medical education

credits for physicians

Dec. 20, 2005 — 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 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.

" While the overall rate of CDAD in the GPRD is much lower than in the hospital

setting, it appears to be increasing significantly even in the face of both our

data and another report to suggest that outpatient antibiotic prescribing in the

GPRD is decreasing, " the authors conclude. " Acid-suppressive agents are among

the most frequently prescribed medications in the United Kingdom and North

America, and it is in this context that the contribution of these agents by

potentially increasing the pool of susceptible hosts to the increasing rates of

CDAD needs to be considered and more completely characterized. "

The Canadian Institutes of Health Research and the Canadian Foundation for

Innovation funded this study. One of the authors has disclosed that he or she is

a consultant for AstraZeneca and Altana Pharma.

JAMA. 2005;294:2989-2995

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Carol in IL