Proton Pump Inhibitor Exposure and Colonization With ESBL-Producing Enterobacterales

Background: Colonization by ESBL-producing Enterobacterales drives antimicrobial resistance transmission. Proton pump inhibitors (PPIs) alter gastric pH and gut flora, potentially increasing colonization risk with enteric bacteria. However, evidence on the association between PPI exposure and ESBL-producing Enterobacterales colonization remains mixed. Methods: The study is a systematic review and meta-analysis according to the PRISMA 2020 criteria. We searched MEDLINE, Embase, and the Cochrane Library for observational studies assessing PPI exposure and ESBL-producing Enterobacterales colonization through December 2025. ORs were calculated using a random-effects meta-analysis model with Hartung-Knapp adjustments. Sensitivity analyses assessed the effect of using broader definitions of acid suppression exposure as well as alternative statistical models. Results: Three studies met the criteria for primary pooling of PPI exposure and ESBL colonization. Pooled analysis demonstrated a directionally increased but imprecise association (OR: 1.91, 95% CI: 0.34-10.91) with substantial heterogeneity ( I 2 =77%). Sensitivity analysis, including five studies with broader acid suppression exposure, yielded a smaller but directionally consistent estimate (OR: 1.49, 95% CI: 0.75-2.97; I 2 ≈ 70%). Sensitivity analyses were exploratory and did not overcome the imprecision and heterogeneity of the evidence base. Publication bias assessment was not performed because of the small sample size. Conclusions: Currently available data are insufficient to establish an association between PPI exposure and ESBL colonization. The wide confidence intervals and substantial heterogeneity render these findings hypothesis-generating rather than conclusive. Larger, methodologically robust prospective studies are needed before clinical or public health recommendations can be made.