Risk Factors of Drug-Resistant Enterobacterales Infections in Patients Receiving Proton Pump Inhibitors

Abstract

Introduction:
Proton pump inhibitors (PPI) are commonly prescribed as stress ulcer prophylaxis in non-critical patients, especially those with major adverse cardiac and cerebrovascular events (MACCE). However, PPI use has been associated with a higher risk of drug-resistant Enterobacterales (DRE) infections. It is still unclear whether PPI use in patients with cerebrovascular accidents (CVA) and acute coronary syndromes (ACS) further increases their risk of DRE infections. This study aimed to explore the risk factors, including MACCE, and the incidence of DRE infections among patients receiving PPI.
Methods:
This retrospective cohort study examined all adult patients who received PPI and were admitted to Hospital Sultanah Maliha, Langkawi, Kedah, Malaysia, between March 1, 2022, and February 28, 2023. The study analyzed the relationship between MACCE and other covariates, with the risk of DRE infections using Cox regression. The first positive DRE culture identified during the study period was treated as an event for the analysis. The effects of covariates on DRE infections were reported as hazard ratios (HR).
Results:
During the study period, 2,585 hospitalized patients were prescribed PPI. Of these, 434 patients (16.8%) were diagnosed with either ACS, CVA or both. The overall incidence of DRE infections among patients prescribed with PPI was relatively low, affecting only 41 patients (1.6%). However, the risk of DRE infections was notably higher among those with concurrent CVA and ACS (10.0%) and those with CVA alone (6.4%). Patients with CVA had a 3.84-fold increased risk of DRE infections compared to those without CVA (95% CI: 1.65 to 8.96; P=0.002). Additionally, patients with frequent hospitalizations (adjusted HR = 1.46, 95% CI: 1.22 to 1.75; P<0.001) and those with a history of antibiotic use (adjusted HR = 2.29, 95% CI: 1.13 to 4.64; P=0.021) also had significantly elevated risks of contracting DRE infections.
Conclusion:
In addition to PPI use, patients with CVA who experienced frequent hospitalizations and had a history of antibiotic use were found to have a higher risk of DRE infections.