[PHNUTR-L] Proton Pump Inhibitors Linked Anew to C. Difficile-Associated Disease

[Kathrynne Holden, MS, RD]

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Proton Pump Inhibitors Linked Anew to C. Difficile-Associated Disease
 
http://www.medpagetoday.com/Gastroenterology/InflammatoryBowelDisease/dh/4181 
	
   	
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.
Action Points

     * 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 
fulminant colitis.

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 
prescription.

"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 
accompanying commentary.

"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. 
difficile-associated disease.

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 
severe disease.

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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