Editorial: Proton Pump Inhibitors and the Changing Face of Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) remains one of the most frequent and severe infectious complications in decompensated cirrhosis, associated with high in-hospital mortality and poor long-term outcomes [1]. Prompt diagnosis and sufficient empiric antibiotic therapy are essential, yet their success depends heavily on anticipating the likely causative pathogen spectrum [1-3]. Normally, gram-negative enteric bacteria have been considered the predominant causative pathogens, reflecting pathological bacterial translocation of intestinal microbiota [2]. Proton pump inhibitors (PPIs) are widely prescribed in patients with cirrhosis (up to 60%), often without a compelling evidence-based indication (approximately 25%) [4]. Several observational studies have reported exposure to PPI is associated with infections, decompensation and liver-related mortality in cirrhosis [5], with meta-analyses indicating a 1.8-fold increased risk of SBP [6]. Notably, Mahmud et al. also demonstrated a reduced mortality from upper gastrointestinal bleeding when PPIs were administered with a proper indication [5]. Whether discontinuation of unnecessary PPI therapy improves outcomes is an active area of clinical investigation in the multicentre, randomised, double-blind STOPPIT trial [7]. In this context, the current multicentre retrospective study by Kitchen et al. [8] provides clinically important evidence that proton pump inhibitor (PPI) therapy may influence not only SBP risk but also its microbiological spectrum toward gram-positive bacteria with a higher proportion of Enterococcus spp., Streptococcus spp., and Staphylococcus aureus. Conversely, gram-negative organisms such as Escherichia coli predominated in patients without PPI therapy. Importantly, PPI use remained an independent predictor of gram-positive SBP even after adjustment for nosocomial acquisition and liver disease severity. This is in line with a previous prospective randomised controlled clinical trial demonstrating a predominance of oral microbiota over gut-derived taxa in healthy volunteers [9] receiving PPI therapy. Gastric acid suppression may impair intestinal barrier function, promote intestinal dysbiosis, facilitate small intestinal bacterial overgrowth (SIBO), and increase the bacterial translocation rate [10], all of which are central processes in the pathogenesis of SBP. A particularly important contribution of the current study is the marked increase in enterococcal SBP among PPI-treated patients. This has major therapeutic implications, as enterococci are intrinsically resistant to third-generation cephalosporins, the standard empiric therapy for community-acquired SBP [2]. Notably, the emergence of enterococcal SBP has been described previously: Several groups, including our group, documented enterococci as increasingly relevant pathogens over a 12-year period, associated with worse outcomes [3]. For nosocomial SBP, where resistant gram-positive organisms are more common, empiric strategies should be tailored according to local epidemiology and resistance patterns [2]. Beyond antimicrobial considerations, the findings reinforce the importance of PPI stewardship in cirrhosis. Although retrospective culture-positive cohorts cannot establish causality, these findings underscore an underappreciated dimension of PPI-associated harm: not simply more infections, but different infections and a poorer outcome. Incorporating medication exposure beyond antibiotics into pathogen risk stratification may therefore improve empiric SBP management and consequently, patient outcome and support a more restrictive use of over-the-counter drugs like PPI. P. A. Reuken: conzeptualisation, writing and editing, review, supervison. S. Quickert: writing and editing, review. The authors have nothing to report. This article is linked to Kitchen et al. paper. To view this article, visit https://doi.org/10.1111/apt.70593. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.