Netherlands: Study Links Proton Pump Inhibitors to Drug-Resistant Bacteria

A recent study published in JAMA Network Open has shown that the use of proton pump inhibitors (PPIs) among adult hospitalized patients is linked to an increased risk of acquiring multidrug-resistant bacteria. PPIs are medications used to control heartburn and other gastrointestinal issues.

The study showed that hospitalized patients using proton pump inhibitors had a 50% greater risk of acquiring extended-spectrum beta-lactamase (ESBL)- or carbapenemase-producing Enterobacterales. Patients who used PPIs twice a day had a slightly higher risk.

The findings reinforce the need to promote the judicious use of PPIs to lessen the risk of acquiring drug-resistant Enterobacterales among hospitalized patients. Resistance to ESBLs and carbapenemases is recognized as an increasingly significant problem for public health. Concerns have risen that PPIs, which are widely overused (about 30%-50% are overprescribed), may increase the colonization risk with drug-resistant microorganisms. Possible confounding by lifestyle-associated factors and disease severity casts doubt on this association, and whether the risk is dose-dependent is unknown.

Against the above background, Roel P. J. Willems from Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands, and colleagues aimed to assess the association between the use of PPIs and the risk of acquiring drug-resistant Enterobacterales and to examine interactions with possible microbiome-altering agents in a nested case-control study.

The study included 2239 hospitalized adult patients identified from a database of Amsterdam University Medical Centers between 2018 to 2021. Patients in the case group had newly detected ESBL or carbapenemase-producing Enterobacterales. Patients with negative results for ESBL- and carbapenemase-producing Enterobacterales were assigned to the control group using risk-set sampling. They were then matched on a 5:1 ratio with patients in the case group by culture, date, and age. A second validation case-control study included matched pairs (1:1 ratio; 94 in each group) of prospectively enrolled patients.

The primary exposure was PPI use and clinical data at 30 days, and the secondary exposure was at 90 days before the culture date. Adjusted incidence rate ratios of ESBL- or carbapenemase-producing Enterobacterales acquisition by time risk windows and PPI dose were estimated.

Study Findings

• Among 2239 hospitalized patients (51.1% male; mean age, 60.9 years), 374 were in the case group (51.6% male; mean age, 61.1 years), and 1865 were in the matched control group (51.0% male; mean age, 60.9 years).
• The aIRR for PPI use overall was 1.48 at 30 days.
• Sensitivity analyses and the analysis of the pair-matched study with prospectively enrolled patients (aIRR, 2.96) yielded similar results; findings were consistent in subgroups and corroborated by a negative-control exposure analysis.
• The authors found no association with microbiome-disturbing agents; antibiotics and laxatives were independently associated with a more than 2-fold increase in acquisition risk (antibiotics: aIRR, 2.78; laxatives: aIRR, 2.26).

"Our findings support the PPI's role as an independent risk factor linked with acquiring ESBL- or carbapenemase-producing Enterobacterales," the researchers wrote. "Given the wide misuse of PPIs, its judicious use is warranted to prevent the associated acquisition of ESBL potentially- or carbapenemase-producing Enterobacterales."

Reference

Willems RPJ, Schut MC, Kaiser AM, et al. Association of Proton Pump Inhibitor Use With Risk of Acquiring Drug-Resistant Enterobacterales. JAMA Netw Open. 2023;6(2):e230470. doi:10.1001/jamanetworkopen.2023.0470