Altered Pathogen Spectrum of Spontaneous Bacterial Peritonitis in Patients Treated With Proton Pump Inhibitors

Background: Proton pump inhibitor (PPI) treatment leads to significant changes in the gut microbiota composition. We hypothesized that these alterations may transfer into distinct changes in the causative agents of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. Aims: To investigate the impact of PPI treatment on the pathogen spectrum of SBP. Methods: A total of 227 cirrhosis patients with culture-positive SBP from two German tertiary care centers were included and the pathogen spectrum of SBP was analysed with respect to PPI treatment. Results: In the PPI-group, gram-positive bacteria were significantly more common compared to the non-PPI-group (62.1% vs. 34.0%, p < 0.001). This involved increased abundances of Enterococcus spp. (22.0% vs. 8.0%), Streptococcus spp. (14.7% vs. 6.0%) and Staphylococcus aureus (15.8% vs. 8.0%). Importantly, more than half of the Enterococcus isolates were susceptible only to antibiotics with extended gram-positive activity. Conversely, gram-negative bacteria were significantly more frequent in the non-PPI-group compared to the PPI-group (64.0% vs. 40.7%, p = 0.003), primarily due to a higher prevalence of E. coli (40.0% vs. 20.3%). In uni- and multivariable logistic regression analyses, PPI use was an independent predictor of gram-positive SBP (OR 2.719, 95% CI 1.343-5.506, p = 0.005), adjusted for nosocomial infection (OR 2.609, 95% CI 1.464-4.650, p = 0.001) and Child-Pugh score (OR 0.684, 0.552-0.848, p < 0.001). Conclusions: PPI treatment is associated with increased abundances of gram-positive pathogens, including Enterococcus spp., in culture-positive SBP. This result can help guide empiric antibiotic therapy of SBP.