Document Detail

Examination of potential mechanisms to explain the association between proton pump inhibitors and Clostridium difficile infection.
MedLine Citation:
PMID:  19667292     Owner:  NLM     Status:  MEDLINE    
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 degrees 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.
Michelle M Nerandzic; Michael J Pultz; Curtis J Donskey
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-08-10
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  53     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-22     Completed Date:  2009-12-14     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4133-7     Citation Subset:  IM    
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
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MeSH Terms
Anti-Bacterial Agents / therapeutic use*
Cecum / microbiology
Clostridium Infections / drug therapy*,  microbiology
Clostridium difficile / drug effects*,  physiology*
Hydrogen-Ion Concentration
Intestines / microbiology
Proton Pump Inhibitors / pharmacology,  therapeutic use*
Spores, Bacterial / drug effects
Stomach / microbiology
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Proton Pump Inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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