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Proton Pump Inhibitors and the Risk for Clostridium difficile Infection

Giuseppe Famularo, MD, PhD; Laura Gasbarrone, MD; Claudio De Simone, MD
JAMA. 2009;302(1):31-32. doi:10.1001/jama.2009.901
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To the Editor: There is an increasing incidence of community-acquired Clostridium difficile infection (CDI) among patients regarded as low risk because they were not exposed to antimicrobial therapy.1 In his Clinical Crossroads article discussing CDI, Dr Kelly2 did not mention the potential role of the excess use of proton pump inhibitors (PPIs) in hospitals and in the community.

The inhibition of gastric acid secretion by PPIs could be an important mechanism in the increasing incidence of CDI because it is thought to suppress a fundamental physiologic defense mechanism against ingested bacteria and spores. The vegetative form of C difficile has been shown to survive in gastric contents with a raised pH,3 which could explain why patients using PPIs may be prone to colonization with C difficile. This is supported by the experimental finding that the risk of acquiring active CDI and the severity of the resulting colitis are similar when animals are exposed to either PPIs or antibiotics.4 However, it is unclear whether giving PPIs to patients who are also taking antibiotics could further increase the susceptibility to CDI; more well-designed epidemiologic studies are needed to assess this hypothesis.

Up to 70% of patients using PPIs have no appropriate indication for gastric acid suppression, and being treated with antimicrobials is not an appropriate indication for PPIs.5 Until it is known whether avoidance of PPIs can protect against C difficile, we recommend being much more conservative in their use, especially in combination with broad-spectrum antibiotics.

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Dial S, Kezouh A, Dascal A, Barkun A, Suissa S. Pattern of antibiotic use and risk of hospital admission because of Clostridium difficile infection.  CMAJ. 2008;179(8):767-772
PubMedCrossRef
Kelly CP. A 76-year-old man with recurrent Clostridium difficile–associated diarrhea: review of C difficile infection.  JAMA. 2009;301(9):954-962
PubMedCrossRef
Jump RL, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C difficile–associated diarrhea?  Antimicrob Agents Chemother. 2007;51(8):2883-2887
PubMedCrossRef
Kaur S, Vaishnavi C, Prasad KK, Ray P, Kochhar R. Comparative role of antibiotic and proton pump inhibitor in experimental Clostridium difficile infection in mice.  Microbiol Immunol. 2007;51(12):1209-1214
PubMed
van Vliet EP, Otten HJ, Rudolphus A,  et al.  Inappropriate prescription of proton pump inhibitors on two pulmonary medicine wards.  Eur J Gastroenterol Hepatol. 2008;20(7):608-612
PubMedCrossRef

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Dial S, Kezouh A, Dascal A, Barkun A, Suissa S. Pattern of antibiotic use and risk of hospital admission because of Clostridium difficile infection.  CMAJ. 2008;179(8):767-772
PubMedCrossRef
Kelly CP. A 76-year-old man with recurrent Clostridium difficile–associated diarrhea: review of C difficile infection.  JAMA. 2009;301(9):954-962
PubMedCrossRef
Jump RL, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C difficile–associated diarrhea?  Antimicrob Agents Chemother. 2007;51(8):2883-2887
PubMedCrossRef
Kaur S, Vaishnavi C, Prasad KK, Ray P, Kochhar R. Comparative role of antibiotic and proton pump inhibitor in experimental Clostridium difficile infection in mice.  Microbiol Immunol. 2007;51(12):1209-1214
PubMed
van Vliet EP, Otten HJ, Rudolphus A,  et al.  Inappropriate prescription of proton pump inhibitors on two pulmonary medicine wards.  Eur J Gastroenterol Hepatol. 2008;20(7):608-612
PubMedCrossRef
July 1, 2009
Ciarán P. Kelly, MD
JAMA. 2009;302(1):31-32.
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