Do PPIs Increase the Risk of Community-Acquired Pneumonia? Findings from an Updated Meta-Analysis

Do PPIs Increase the Risk of Community-Acquired Pneumonia? Findings from an Updated Meta-Analysis
Riley Larson, PharmD, M Health Fairview Bethesda | Walgreens

Background: Emerging evidence has explored the potential harms of utilization of proton pump inhibitors (PPIs). PPIs are commonly prescribed to treat dyspepsia, peptic ulcers, and gastroesophageal reflux disease (GERD). Numerous small-scale studies have examined a potential increased risk of community-acquired pneumonia (CAP). However, this correlation has not been assessed on a large-scale–warranting the assessment via a meta-analysis.

Objective: The objective of this meta-analysis was to systematically assess the correlation between PPI utilization and CAP in adults.

Study Design: Studies between January 1, 2004 and February 1, 2021, examining the incidence of CAP with PPI use, were pulled from the literature. Inclusion criteria included clinical studies with a clear presentation of the incidence of CAP in both placebo and treatment arms. Studies examining H. pylori, those not written in English, or those with insufficient data for estimation of odds ratios (OR) and 95% confidence interval (CI) were excluded from the meta-analysis. Seven case-control, four cohort, and two observational studies were included in this meta-analysis, encompassing over 700,000 PPI users and 1.3 million nonusers. The primary outcome was the incidence of CAP overall. The secondary outcome specified PPI duration, examining the incidence of CAP for patients prescribed PPIs for less than 30 days.

Results: After a random effect model was applied due to significant heterogeneity between the studies, the OR of developing CAP in patients who used PPIs was 1.37 (95% CI 1.22 - 1.53) when compared to non-PPI users. Therefore, utilization of PPIs could significantly increase the occurrence of CAP compared to non-PPI users.

Four of the 13 studies (N = 6,684) specifically examined the relationship of PPI use for less than 30 days. The OR of contracting CAP in patients prescribed PPIs for less than 30 days was 1.49 (95% CI 1.34 - 1.66) compared to non-PPI users. This demonstrates that even PPI use for less than 30 days can significantly increase the incidence of CAP compared with non-PPI use.

Conclusion: Utilization of PPIs could increase the likelihood of CAP when compared to not using PPIs. Given this meta-analysis included studies with lower quality study designs, more research is warranted to confirm the relationship between PPI use and CAP. However, given the availability of the literature, these results may help with risk-benefit conversations with patients when evaluating if prescribing PPIs is appropriate.


  1. Xun X, Yin Q, Fu Y, He X, Dong Z. Proton pump inhibitors and the risk of community-acquired pneumonia: an updated meta-analysis. Ann Pharmacother. 2022;56(5):524-532. doi:10.1177/10600280211039240.