Clinically important interaction between statin drugs and Clostridium difficile toxin?

Research output: Contribution to journalArticle

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Abstract

Clostridium difficile associated disease (CDAD), a common type of antibiotic associated diarrhea, is increasing in frequency and affecting patients outside of traditional populations. At one time CDAD exclusively occurred in hospitalized patients or frail elderly patients receiving antibiotic therapy. It is now occurring more commonly in younger patients who are relatively healthy and may not be receiving antibiotics. Co-factors that might explain this increase incidence and changing demographic are of great public health interest. Recent investigations have identified gastric acid suppression, particularly via proton pump inhibitors, as a risk factor for the development of CDAD by mechanisms which are not entirely clear. C. difficile toxin comes as two major forms that are closely related, toxin A and toxin B and both are able to produce CDAD. These toxins have a glucosyltransferase domain that glucosylates actived Rho, a small GTP binding protein involved in multiple cellular signaling pathways. Glucosylation inactivates Rho and modifies cell cycle, cytoskeletal and inflammatory pathways. The lipid lowering drugs called statins also inhibit Rho but at an earlier step in the Rho pathway. Statins inhibit the isoprenylation of Rho and therefore inhibits membrane anchoring a key step in Rho signaling. We propose that statins potentiate C. difficile toxin effects on colonic epithelium which leads to an increased risk of CDAD. We present preliminary data from a retrospective cohort which demonstrated an increased rate of CDAD in patients receiving statins compared to non-statin controls. The weight of the evidence leads to our hypothesis that statins interact with C difficile toxin A and B causing an increase in the rate and severity of CDAD.

Original languageEnglish (US)
Pages (from-to)1045-1047
Number of pages3
JournalMedical Hypotheses
Volume73
Issue number6
DOIs
StatePublished - Dec 1 2009

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Clostridium difficile
Pharmaceutical Preparations
Anti-Bacterial Agents
Prenylation
Glucosyltransferases
Frail Elderly
rho GTP-Binding Proteins
Proton Pump Inhibitors
Gastric Acid
Diarrhea
Cell Cycle
Epithelium
Public Health
Demography
Lipids
Weights and Measures
Membranes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clinically important interaction between statin drugs and Clostridium difficile toxin? / McGuire, Timothy R; Dobesh, Paul P; Klepser, Donald G; Rupp, Mark Edmund; Olsen, Keith.

In: Medical Hypotheses, Vol. 73, No. 6, 01.12.2009, p. 1045-1047.

Research output: Contribution to journalArticle

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