[PHNUTR-L] Proton Pump Inhibitors Linked Anew to C.
Kathrynne Holden, MS, RD
fivestar at nutritionucanlivewith.com
Thu Sep 28 07:54:00 PDT 2006
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Proton Pump Inhibitors Linked Anew to C. Difficile-Associated Disease
By Crystal Phend, Staff Writer, MedPage Today
MONTREAL, Sept. 27 -- There is new evidence that proton pump inhibitors
are important contributors to the likelihood of Clostridium
difficile-associated disease. H2-receptor antagonists were exonerated.
* Explain to interested patients that this study adds evidence to
the contention that proton pump inhibitors are important contributors to
the likelihood of Clostridium difficile-associated disease.
* Inform interested patients that this study does not settle the
controversial issue and that a prospective, blinded, controlled
interventional study may be needed to do so.
Proton pump inhibitor exposure increased the odds of C.
difficile-associated disease 3.5-fold, reported Sandra Dial, M.D.,
M.Sc., of the Royal Victoria Hospital in Montréal, and colleagues, in
the Sept. 26 issue of the Canadian Medical Association Journal. They did
not find a significant increase in risk from H2-receptor antagonist
therapy (OR 1.4, 95% CI 0.8 to 2.5).
Antibiotic exposure remained a significant factor in the development of
C. difficile-associated disease, she and colleagues reported.
Although some studies have found proton pump inhibitors to be second
only to antibiotic therapy as a risk factor for C. difficile-associated
disease, other researchers have dismissed the link.
The case-control study by Dr. Dial and colleagues tracked prescriptions
for oral vancomycin with British patients to define community-acquired
C. difficile-associated disease, which ranges from mild diarrhea to
Prior antibiotic exposure yielded an odds ratio of 8.2 (95% CI 6.1 to
11.0) as expected, but 45% of the C. difficile-associated disease cases
were not exposed to antibiotics within 90 days before vancomycin
"Even when sophisticated molecular typing and studies of pathogenesis
have been applied to clonal outbreaks, controversy has ensued over the
relative contribution of antibiotic resistance, environmental and hand
hygiene, and isolation of cases," said microbiologist Richard
Cunningham, Ph.D., of Derriford Hospital in Plymouth, England, in an
"Add to this increasingly polarized debate the issue of proton pump
inhibitors. In some studies, use of these drugs has been found to be
second only to antibiotic therapy as a risk factor for C.
difficile-associated disease, whereas other researchers have dismissed
use of proton pump inhibitors as merely reflecting confounding variables
such as age and prolonged hospital stay."
The current study included 317 patients in the United Kingdom's General
Practice Research Database who had not been admitted to a hospital in
the year before their first oral vancomycin prescription, recorded in
the database from 1994 to 2004. Patients who had a clinical diagnosis or
toxin-positive laboratory result recorded 30 days to a year before the
prescription date were excluded as possible relapses. The mean age was
65.0 years and female gender predominated.
Each case was matched to up to 10 control subjects selected from the
database who attended the same general practice, were matched by age,
had not been admitted to the hospital in the year prior, had not
received a prescription for oral vancomycin therapy and were neither
toxin positive nor had had a clinical diagnosis of C.
Proton pump inhibitor use was present in 19.2% of cases and 5.0% of the
3,167 controls. H2-receptor antagonist therapy was used by 7.3% of cases
and 3.5% of controls.
All odds ratios were adjusted for gender, concurrent prescriptions for
non-steroidal anti-inflammatory drugs or aspirin, and for comorbid
conditions including inflammatory bowel disease, diverticular disease,
peptic ulcer disease, gastresophageal reflux disease, Helicobacter
pylori-associated disease, cancer, and methicillin-resistant
Staphylococcus aureus infection.
Other factors that were significantly more common in cases than controls
included history of renal failure, inflammatory bowel disease and cancer
and previous diagnosis of methicillin-resistant S. aureus infection.
The researchers noted that defining C. difficile-associated disease by
vancomycin prescription may have biased the results. Metronidazole is
suggested as the first-line agent for the treatment of C.
difficile-associated disease and is significantly less expensive than
vancomycin, so the study may have unintentionally looked at only more
Also, if vancomycin was prescribed as a second-line agent to failed
antibiotic therapies, this could have increased the estimated effect of
exposure to previous antibiotic agents. Indeed, compared to other
studies using different definitions of C. difficile-associated disease,
there was a higher proportion of patients who had previously been
exposed to antibiotics among cases: 55% versus 34% defined by a positive
toxin assay result and 38% defined by physician diagnosis.
Yet defining C. difficile-associated disease by vancomycin prescription
is "reasonable, because [it] is the only indication for this antibiotic
by this route," commented Dr, Cunningham.
However, he cautioned that this study does not definitively answer
whether proton pump inhibitors are causally linked to C.
difficile-associated disease. "Opinions are so polarized on this issue
that only a prospective, blinded, controlled interventional study is
likely to resolve it," he wrote.
The study was funded by the Canadian Institutes of Health Research and
the Canadian Foundation for Innovation.
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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