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PPI Use Upped Risk for Community-Acquired Pneumonia


Proposed mechanisms for the association include PPI-induced acute pH dysregulation and alteration of the gut microbiome.

Outpatient use of proton pump inhibitors (PPIs) can significantly increase the risk for community-acquired pneumonia, according to the results of a meta-analysis published recently in PLoS One.

Considering this increased risk, researchers led by Allison A. Lambert, of the division of pulmonary and critical care at Johns Hopkins University, said that providers should consider alternative regimens in cases where the benefits of PPIs may be uncertain.

According to the study, PPIs are among the most commonly prescribed medication in the United States, but studies have shown that as few as 35% of patients prescribed this class of medication have an appropriate indication documented. In addition to some of the known PPI side effects, the authors  hypothesized that community-acquired pneumonia may also be a consequence of the drugs’ use.

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Fifteen of the 26 studies included in the analysis reported a statistically significant increased risk for community-acquired pneumonia with the use of PPIs, but 11 reported no significant association. Overall, the meta-analysis estimated a 1.5-fold increased risk for community-acquired pneumonia with outpatient PPI use (RR=1.49; 95% CI, 1.16-1.92).

“When limiting our analysis to studies that measured PPI exposure separately from other gastric acid suppressant drugs, we found that the association between PPI exposure and community-acquired pneumonia remained similar to our primary analysis and heterogeneity remained high,” the researchers wrote.

The highest risk for pneumonia was found among those patients taking a PPI for less than one month (OR=2.10; 95% CI, 1.39-3.16) compared with those taking no therapy. The risk for pneumonia decreased and lost significance as the duration of therapy increased.

“Our findings are consistent with the theory that proton-pump inhibitor therapy may lead to community-acquired pneumonia both through acute pH dysregulation and alteration of the gut microbiome,” the researchers wrote. “Community-acquired pneumonia risk was greatest during the first month of therapy, which is the time period during which the aero-digestive microbiome may be in greatest flux.”

Finally, patients aged 65 years or older had significantly increased risk for community-acquired pneumonia with outpatient PPI use compared to those not taking therapy (OR=1.33; 95% CI, 1.13-1.58).

The researchers also explored whether there was an association between risk of hospitalization for community-acquired pneumonia and PPI use and found a 1.61-fold increased risk among outpatient PPI  users.

“Given the widespread usage of proton pump inhibitor therapy, often without an appropriate indication, the excess risk of community-acquired pneumonia among proton pump inhibitor users could translate into a substantial burden on the healthcare system. Moreover, the increased risk of hospitalization for community-acquired pneumonia underscores the potential clinical and financial impact of this adverse effect,” the researchers wrote. “Careful consideration of the risks, benefits and alternative treatment options should occur with all proton pump inhibitor prescriptions.”


Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One. 2015 Jun 4;10(6):e0128004. doi: 10.1371/journal.pone.0128004.


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