In this rodent model, we studied the effect of PPIs on intra-abdominal sepsis after gastric spillage. From our results, we saw a higher rate of bacterial contamination and abscess formation in the study group. While our data for abscess was not statistically significant, there appeared to be a trend towards higher rate of infection. Of the cultures that were positive, there was a higher rate of Gram-negative (enteric) infection in the PPI-treated group versus the control group. This data supports the conclusion of several studies on rodents and humans that found an association between acid suppression and bacterial overgrowth/infection [
6‐
9]. In a landmark study by Franklin et al., it was found that the previously held notion of a “sterile” foregut was challenged by the finding of polymicrobial gastric flora. This study was the first to show an increase in colony-forming units (CFUs) and an increase in enteric pathogens as the gastric pH increases [
10]. Our study observed similar findings with loss of comensural organisms such as
Lactobacillus, and increased growth of enterics such as
E. coli and
Proteus species. More recently, the chronic use of PPI has been associated with community-acquired
Clostridium difficile colitis [
11] and a meta-analysis found an association with acid suppression and enteric infection [
12]. Similarly, in two retrospective human studies, the crude odds ratio for development of spontaneous bacterial peritonitis among PPI users versus nonusers ranged from 1.22 to 7.0 [
8,
13]. A human study by Narula et al. found that transgastric instrumentation contaminates the peritoneal cavity and those patients on PPIs have a higher bacterial load compared with nonusers [
7]. In this small series of 50 patients, there was no observable adverse clinical outcome as a result of a higher bacterial load; however these patients were all treated with preoperative antibiotics. Our study demonstrates similar clinical findings to those of Narula, although with the added benefit of the animal model, we were able to demonstrate a higher rate of peritoneal infection with a trend towards significance (
p = 0.08) in the study group. Despite these findings, there was no observable difference between the groups with regards to subjective or objective criteria such as behavior, activity level, absolute neutrophil count or C-reactive proteins levels. Our rat model raises the question as to whether the alterations in gastric pH as a result of PPIs and subsequent changes in gut flora are of clinical significance necessitating changes in clinical practice.
The limitations of our study was that we worked with a set “volume” of gastric aspirate that was chosen as a percentage of total body weight of the rat model, i.e., 2 cc/250 g rat = 320 cc/60 kg human. It is difficult to assess whether an increase in bacterial load or “volume” would have led to a different outcome, or whether one can extrapolate human outcomes from a rodent model. In addition, our experiment design could have more closely approximated the clinical scenario of NOTES by using open or closed gastrotomy with peritoneal contamination instead of directly injecting gastric contents into the peritoneum, which may have caused an increase rate of abscess formation.
The results of this study are suggestive of an increased risk of intraperitoneal infection with proton-pump inhibitors, but it remains unclear if simple measures such as appropriate antibiotic coverage, aggressive sterile technique, and better clearance of secretions will reduce this risk. More investigations are warranted to address this issue before alterations in clinical practice can be recommended.