Proton Pump Inhibitors and ESBL

We have written frequently about the many HAI and MDRO that have been linked to PPI use including VAP, CAP, HAP in non-ICU settings, SBP in patients with cirrhosis, and, of course, C. difficile. In the US, PPIs are the third most prescribed medication, they are addictive since withdrawal symptoms can develop and are now available over-the-counter.

Researchers at Amphia Hospital, an 850-bed teaching facility in the Netherlands, completed two prevalence studies (November 2014 and 2015) on all adult patients who had stayed for no more than 2 days. The cross-section study just published in CID (free full text) linked rectal carriage of ESBL-producing Enterobacteriaceae to pre-admission use of PPI and H2-antagonists among other factors.

Rectal cultures were available from 570 patients and 259 (45%) had a history of PPI use, while very few used H2-blockers or antacids. I have included the univariable and multivariable analyses below. More than concurrent antibiotic use or prior hospital admission, PPIs were associated with four times the risk of ESBL rectal carriage. (OR 3.89, 95% CI 1.65-9.19).  This is a very nicely completed study and provides more evidence supporting the inclusion of PPIs targets in our "antimicrobial" stewardship programs.

CDI? Think PPI

Following up on last years MMWR that reported that "nearly 75% of all Clostridium difficile infections (CDI) related to U.S. health care have their onset outside of hospitals", CDC researchers have released a new study in JAMA Internal Medicine looking specifically at the epidemiology of community-associated CDI. The study used data from the Emerging Infections Program, which began to actively collect CDI data in 10 states starting in 2009. This report uses data from 984 patients collected over 29 months with true community-onset CDI, as they excluded community-onset, healthcare facility associated infections.

Somewhat surprisingly, 36% of patients had not received antibiotics and 18% had no outpatient health care exposure. Not surprisingly, 31% of those who had not been exposed to antibiotics had been exposed to PPIs.  I highlighted the risk of CDI from PPIs in my ICPIC talk last month when I discussed this meta-analysis by Kwok and colleagues. In this CDC study, those patients lacking significant outpatient healthcare exposure were also more likely to be exposed to infants and household members with active outpatient healthcare exposure suggesting a potential route of transmission. I agree with the authors primary conclusion that a reduction of outpatient PPI use may be necessary to reduce the risk of CDI. As Mike' pointed out four years ago, PPIs are also associated with HAP, VAP, and SBP, so there are many reasons to be concerned about PPIs.

There is an excellent accompanying editorial by some guy named Kent Sepkowitz, who discusses the "PPI-zation" of the US and the difficulties facing any public health initiative targeting PPIs. For one, PPIs are the third most utilized drug in the US and they are addictive since discontinuation is associated with withdrawal symptoms.  For another, unlike antibiotics, PPIs are widely available over the counter and supported by huge advertising campaigns. Looks like PPIs are here to stay...

PPIs: The Dark Side

Two new studies add two more infections to the list of those that are associated with the use of proton pump inhibitors (PPIs). Previous papers have shown that ventilator-associated pneumonia, community-acquired pneumnonia, and Clostridium difficile associated disease are associated with PPI use. The large cohort study in today's JAMA found that PPIs were associated with a significant increase in the rate of hospital-acquired pneumonia in non-ICU, non-ventilated patients. And this month's American Journal of Gastroenterology contains a study showing that PPIs are associated with a higher rate of spontaneous bacterial peritonitis in patients with cirrhosis. Given the mounting evidence of risk for infection, coupled with the high frequency of use in hospitalized patients (the JAMA paper found that 52% of inpatients were prescribed PPIs), hospitals should probably begin to restrict the use of these agents.