Microbial evaluation of proton pump inhibitors and the risk of pneumonia

Background: Recent initiation of proton pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonization of the oropharynx by gastrointestinal bacteria. Aim of this study was to assess the causal pathway by considering microbial etiology of pneumonia and indications for initiation of PPI treatment. Methods: This was a population-based case-control study with 430 cases with pneumonia and 1720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Results: Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.2, 95% CI 1.4 – 7.2). Oropharyngeal bacteria were evenly distributed among current, past and non-users of PPIs (p=0.41). Only in 5 patients (1.2%) with pneumonia (2 current users and 3 non users), gastrointestinal bacteria were identified. Excluding patients who possibly were prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. Causal Pathogens of CAP in relation to PPI use All Non Current Past n=430 (%) n=307 (%) n=103 (%) n=20 (%) Oropharyngeal bacteria* 166 (39) 119 (39) 42 (41) 5 (25) Gastrointestinal bacteria † 5 (1.2) 3 (1.0) 2 (1.9) 0 (0.0) * S. pneumoniae , H. influenzae , S. aureus , H. parainfluenzae and other streptococci. † E. coli and K. pneumoniae . Conclusions: This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment is started recently. Protopathic bias nor shifts in microbial aetiology seem to explain the association.