Association between recent use of proton pump inhibitors and nontyphoid salmonellosis: a nested case-control study

Nontyphoid salmonellosis (NTS) is one of the most common foodborne diseases worldwide, affecting millions of persons each year [1, 2]. Usually acquired by consumption of contaminated food, especially eggs and poultry products, NTS may cause gastroenteritis, bacteremia, and focal infections [3]. Predisposing host factors include gastric hypoacidity [1], diabetes [3, 4], autoimmune diseases [1, 4], cancer [5], hepatic cirrhosis [3], gallstones [1], previous gastrointestinal surgery [6], AIDS [7, 8], and prior use of antimicrobial agents [3, 7, 8]. Proton pump inhibitors (PPIs) have also been associated with NTS [9–11]. This association is thought to be due to disruption of the natural gut microbial ecology [12] caused by inhibition of gastric acid secretion, mucosal permeability [13], and neutrophil bactericidal activity [14]. Most studies have shown an association between PPI use and susceptibility to NTS but failed to consider the confounding effects of host factors that enhance susceptibility to NTS [9–11]. A recent study, which controlled for individual confounding factors by using the patients as their own control over a 12-month period, found no association between PPIs use and NTS, suggesting that predisposing factors other than PPIs may contribute to the increased rate of NTS [15]. Because of the conflicting results in the literature, problems of selection bias [16], and differences in the intervals of time between the use of a PPI and onset of NTS we believed that a large, community-based study was needed to adjust for the effect of predisposing host factors and to determine the critical interval between use of a PPI and the onset of NTS. To accomplish this we conducted a nested case-control study, matching for demographic and predisposing host factors for NTS. The Taiwan National Health Insurance Research Database (NHIRD) 2000–2010 was used to identify a large number of case patients and controls during an 11-year period.