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Two studies link acid suppression therapy with increased risk of C. difficile infection

Friday, June 04 2010 | Comments

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What's This? Increased levels of gastric acid suppression therapy are associated with an increased risk of Clostridium difficile infection, according to results of a recent analysis conducted among patients treated at the Beth Israel Deaconess Medical Center in Boston.

In addition, results of a second study in which data from the Veterans Affairs New England Healthcare System were used extend these findings by demonstrating a link between proton pump inhibitor (PPI) use during treatment for C. difficile infection and an increased risk of C. difficile recurrence.

In the first study, researchers conducted a secondary analysis of data that was collected prospectively on 101,796 discharges during a 5-year period. The investigators evaluated the link between the level of acid suppression therapy (no therapy, histamine-2 receptor agonist [H2RA] therapy, daily PPI therapy, or more frequent PPI therapy) and the subsequent incidence of nosocomial C. difficile infection.

In unadjusted analyses, the risk of nosocomial C. difficile infection increased as the level of acid suppression therapy increased, from 0.3% (95% CI, 0.21%-0.31%) with no such therapy to 0.6% (95% CI, 0.49%-0.79%) with H2RA therapy, 0.9% (95% CI 0.80%-0.98%) with daily PPI therapy, and 1.4% (1.15%-1.71%) with more frequent PPI therapy.

Similarly, in an analysis that adjusted for age, antibiotics, comorbid conditions, and a propensity score that evaluated the likelihood of receiving acid suppression therapy, the odds ratio for C. difficile infection was (vs no acid-suppression therapy) 1.53 (95% CI, 1.12-2.10) with H2RA therapy, 1.74 (95% CI, 1.39-2.18) with daily PPI therapy, and 2.36 (95% CI, 1.79-3.11) with more frequent PPI therapy.

The study authors suggested that the association observed in the current study is both statistically and clinically meaningful. According to these results, they explained, >=1 additional case of nosocomial C. difficile infection would occur with every 533 patients treated with daily PPI therapy (relative to no acid-suppression therapy).

"Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large," they noted. (Howell MD, et al. Arch Intern Med 2010;170:784-790.)

The second analysis was a retrospective cohort study of 1,166 patients with an incident C. difficile infection who were treated with metronidazole or vancomycin hydrochloride sometime between Oct. 1, 2003, and Sept. 30, 2008. Of these patients, 45.2% received oral PPIs within 14 days of the C. difficile diagnosis.

Recurrent C. difficile infection, defined as positive toxin findings from 15 to 90 days after the incident infection, was more common among those who were exposed to PPIs (25.2%) than among those who were not exposed (18.5%).

In an analysis that adjusted for age, choice of initial antibiotic, additional antibiotic exposure, duration of hospital stay, and comorbidities and medication use at baseline, the risk of recurrent C. difficile infection was 42% higher among those exposed to PPIs as compared with the unexposed patients (hazard ratio, 1.42 [95% CI, 1.10-1.83]; P=.008).

The risk of recurrent infection among PPI-exposed patients was highest among patients aged older than 80 years and among those who received additional antibiotics (other than those targeting C. difficile) during follow-up. (Linsky A, et al. Arch Intern Med 2010;170:772-778.)

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