Gastric Acid-Suppressive Agents and Risk of Community-Acquired C. difficile
Gastric Acid-Suppressive Agents and Risk of Community-Acquired C. difficile
Abstract & Commentary
By Malcolm Robinson MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker's bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.
Synopsis: Acid suppression, particularly with proton pump inhibitors (PPIs) is correlated with an increased risk of community-acquired Clostridium difficile colitis.
Source: Dial S, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989-2995.
Clostridium difficile-associated disease (CDAD) is known to be an important and highly destructive pathogenic process in the hospital setting. CDAD also is now recognized as a significant illness in the community as well. For example, a British study found CDAD to be the third most common cause of diarrhea in the general population. In France, 1.5% of antibiotic recipients were prospectively found to develop CDAD. The authors correctly note that gastric acid provides a critical barrier against potential intestinal pathogens, and suppression of acid would be anticipated to be a risk factor for infection with such pathogens. This study involved assessment of patients with at least 2 years of follow-up in a database including 3 million patients and 400 family physicians in the United Kingdom. Antibiotic prescriptions, acid suppressive agents, nonsteroidal anti-inflammatory drugs, and CDAD cases were identified in this group of patients along with potentially important coexisting illnesses.
Of 1672 cases of Clostridium difficile, 1233 (74%) had not been hospitalized in the year prior to diagnosis (thus considered to be community-acquired). Data shown by these authors demonstrated a dramatic increase in CDAD over the past 10 years—graphically correlated with increased PPI prescriptions. Actually, instances of antibiotic administration gradually decreased during this interval. Mean age of CDAD cases was 71 years. For PPIs the relative risk of CDAD was 3.0 (95% CI, 2.5-3.7) and relative risk was 2.5 (95% CI, 1.8-3.4) for H2RA exposure. Additional positive risk factors were inflammatory bowel disease, renal failure, methicillin-resistant Staphylococcus aureus, and cancer. Four earlier case control studies had found a relationship between acid suppression and development of CDAD in the hospital setting. Although prior antibiotic use was the most important risk factor for CDAD in the present community-based study, only 37% of the cases had a history of antibiotic use during the prior 90 days. Thus, most of the cases seemingly occurred in the absence of any antibiotic exposure. The correlation of NSAID use with CDAD remained unexplained by the authors of this paper.
Commentary
PPIs are among the most widely prescribed of all prescription medications, and omeprazole has now been very successfully marketed over the counter. PPIs, like the H2RAs before them, are considered to be extremely safe and well tolerated. However, there is now increasing evidence that antisecretory agents may not be as innocuous as previously believed. In addition to the growing data suggesting the relationship of acid suppression (especially with PPIs) to infections with intestinal pathogens like CDAD, there have also been reports of interference with absorption of vitamins B-12 and C. PPIs have also been implicated as a possible risk factor for pneumonia, and there are continued scattered reports of serious drug interactions with PPIs individually and as a class. It seems likely that NSAIDs may be implicated in the causation of CDAD by their known injurious effects on the intestinal mucosa. The present paper didn't break down NSAIDs into COX-1 and COX-2 varieties, but the relative roles of these NSAID subtypes could be of interest. Physicians should continue to be alert for additional problems that may be associated with acid suppression, an issue of particular significance since these drugs are increasingly recognized as inappropriately prescribed in a great many settings.
Acid suppression, particularly with proton pump inhibitors (PPIs) is correlated with an increased risk of community-acquired Clostridium difficile colitis.Subscribe Now for Access
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