Overuse of PPIs may raise risk of C. diff infections, fractures

Widespread overuse of proton-pump inhibitors appears to increase patients' risk of Clostridium difficile infections and fractures, several recent studies concluded.

One study, which analyzed data on more than 100,000 patients discharged from a tertiary care hospital over five years, found that the risk of nosocomial C. difficile infection increased among patients taking daily proton-pump inhibitors (PPIs) compared with those not taking the drugs (0.3% to 0.6%, respectively) and was highest among patients who took PPIs more than once a day (1.4%). Another retrospective study found that PPI use during C. difficile treatment was associated with a 42% increase in risk of recurrence of infection. Both studies appear in the May 10 Archives of Internal Medicine.

Three other studies in the same issue of Archives bring up other potential risks associated with overuse of PPIs. One study, based on Women's Health Initiative data, looked at the impact of PPI use on fractures in postmenopausal women and concluded that PPIs were associated with an increased risk of spine, lower arm and total fractures (but not hip fracture). In addition, a meta-analysis demonstrated that higher doses of PPIs (equivalent to an 80-mg bolus followed by 8 mg/h for 72 hours or similar dose) were not more effective than lower doses in decreasing the rates of rebleeding, surgical intervention or mortality among patients with bleeding peptic ulcers.

A fifth study found that a guideline on appropriate PPI use decreased inpatient and discharge PPI therapy, but only among patients who were not taking the medication at admission. The overall rate of use was driven up by the high rate of outpatient PPI use at admission.

Overuse of PPIs can be tied to the prevalence of dyspepsia and the propensity of physicians to prescribe a pill rather than consider other possible treatments, said an accompanying editorial. However, for many patients the risks of PPIs may outweigh the benefits, the editorial continued, adding that PPIs are also thought to increase the risk of hospital- and community-acquired pneumonia.

While PPIs relieve symptoms of dyspepsia, they should not be routinely prescribed, especially in the absence of ulcer disease, esophagitis or severe gastroesophageal reflux disease, the editorialist said. Clinicians should offer alternative treatments for functional dyspepsia, prescribe short courses of treatment, and consider discontinuing therapy in asymptomatic patients. In addition, patients who know the risks may want to consider non-drug options such as waiting for symptoms to resolve over time and making behavioral changes.