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Antimicrobial Agents and Chemotherapy, October 2009, p. 4133-4137, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00252-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection{triangledown}

Michelle M. Nerandzic,1 Michael J. Pultz,1 and Curtis J. Donskey1,2*

Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio,1 Geriatric Research, Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio2

Received 21 February 2009/ Returned for modification 6 April 2009/ Accepted 28 July 2009

Proton pump inhibitors (PPIs) have been associated with Clostridium difficile infection (CDI) in several recent studies. However, other studies have not shown this association, and the mechanism by which PPIs might promote CDI has not been elucidated. We hypothesized two possible mechanisms of causation: first, by raising pH, PPIs may prevent gastric contents from killing C. difficile spores; second, gastric contents of PPI-treated patients may promote germination and outgrowth of C. difficile spores. Survival rates of spores from six different strains of C. difficile in acidic gastric contents were assessed using quantitative cultures on selective media. Germination and outgrowth of spores were assessed by heat shock at 80°C, phase-contrast microscopy, and ethanol shock after incubation for 24 h in the gastric contents of patients and in the gastric, small intestinal, and cecal contents of mice. C. difficile spores survived and remained dormant in nonbilious gastric contents with acidic pH. Germination did not occur in unmodified gastric contents of patients but did occur with the addition of taurocholic acid and amino acids. In mice, germination did not occur in gastric contents but did occur in small intestinal and cecal contents. In summary, C. difficile spores survived in acidic gastric contents and did not undergo germination and outgrowth in gastric contents, probably due to lack of essential germinants, such as taurocholic acid. Our results suggest that the effects of PPIs in the stomach do not contribute to the pathogenesis of CDI.

* Corresponding author. Mailing address: Geriatric Research, Education and Clinical Center 1110 (W), Cleveland VA Medical Center, 10701 East Blvd., Cleveland, OH 44106. Phone: (216) 791-3800, ext. 5103. Fax: (216) 229-8509. E-mail: curtisd123{at}yahoo.com

{triangledown} Published ahead of print on 10 August 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4133-4137, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00252-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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