Suppression of Gastric Acid Production by Proton Pump Inhibitor Treatment Facilitates Colonization of the Large Intestine by Vancomycin-Resistant
            <i>Enterococcus</i>
            spp. and
            <i>Klebsiella pneumoniae</i>
            in Clindamycin-Treated Mice

Stiefel, Usha; Rao, A. Gururaj; Pultz, Michael J.; Jump, Robin L.P.; Aron, David C.; Donskey, Curtis J.

doi:10.1128/aac.00522-06

Cited by 28 publications

(31 citation statements)

References 21 publications

(19 reference statements)

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“…It has also been demonstrated that PPIs may have antibacterial activity (13). However, we found that PPI therapy, in the absence of concurrent antibiotic therapy, did not promote colonization by vancomycin-resistant enterococci and Klebsiella pneumoniae, suggesting that these agents do not have significant adverse effects on the indigenous intestinal microflora (23). Our study has limitations.…”

Section: Discussioncontrasting

confidence: 49%

Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection

Nerandzic

Pultz

Donskey

2009

Antimicrob Agents Chemother

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Proton pump inhibitors (PPIs) have been associated with Clostridium difficile infection (CDI) in several recent studies. However, other studies have not shown this association, and the mechanism by which PPIs might promote CDI has not been elucidated. We hypothesized two possible mechanisms of causation: first, by raising pH, PPIs may prevent gastric contents from killing C. difficile spores; second, gastric contents of PPI-treated patients may promote germination and outgrowth of C. difficile spores. Survival rates of spores from six different strains of C. difficile in acidic gastric contents were assessed using quantitative cultures on selective media. Germination and outgrowth of spores were assessed by heat shock at 80°C, phase-contrast microscopy, and ethanol shock after incubation for 24 h in the gastric contents of patients and in the gastric, small intestinal, and cecal contents of mice. C. difficile spores survived and remained dormant in nonbilious gastric contents with acidic pH. Germination did not occur in unmodified gastric contents of patients but did occur with the addition of taurocholic acid and amino acids. In mice, germination did not occur in gastric contents but did occur in small intestinal and cecal contents. In summary, C. difficile spores survived in acidic gastric contents and did not undergo germination and outgrowth in gastric contents, probably due to lack of essential germinants, such as taurocholic acid. Our results suggest that the effects of PPIs in the stomach do not contribute to the pathogenesis of CDI.

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Section: Discussioncontrasting

confidence: 49%

Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection

Nerandzic

Pultz

Donskey

2009

Antimicrob Agents Chemother

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“…Subcutaneous (SQ) ␤-lactam antibiotic doses were equivalent to the usual human doses administered over a 24-hour period (milligrams of antibiotic/gram of body weight) and were as follows: piperacillin-tazobactam, 10.7 mg/0.2-ml dose; ceftriaxone, 1.6 mg/0.2-ml dose. SQ pantoprazole was given at 0.4 mg/0.2 ml (27).…”

Section: Bacterial Strainsmentioning

confidence: 99%

“…We used a well-established murine model (23)(24)(25)(27)(28)(29)(30)(31)(32)(33) to test intestinal colonization resistance to VRE. Mouse groups 1 and 3 received oral gavage with 0.5 ml of normal saline (NS) alone once/day for 3 days, delivered via a stainless steel feeding tube (Perfektum; Popper and Sons), as their microbiota was recovering from the piperacillin-tazobactam.…”

Section: Bacterial Strainsmentioning

confidence: 99%

Gastrointestinal Colonization with a Cephalosporinase-Producing Bacteroides Species Preserves Colonization Resistance against Vancomycin-Resistant Enterococcus and Clostridium difficile in Cephalosporin-Treated Mice

Stiefel

Nerandzic

Pultz

et al. 2014

Antimicrob Agents Chemother

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Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. ␤-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the microbiota. Many bacteria are capable, however, of producing ␤-lactamase enzymes that inactivate ␤-lactam antibiotics. We hypothesized that prior establishment of intestinal colonization with a ␤-lactamaseproducing anaerobe might prevent these adverse effects of ␤-lactam antibiotics, by inactivating the portion of antibiotic that is excreted into the intestinal tract. Here, mice with a previously abolished microbiota received either oral normal saline or an oral cephalosporinase-producing strain of Bacteroides thetaiotaomicron for 3 days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either oral administration of vancomycin-resistant Enterococcus (VRE) or sacrifice and assessment of in vitro growth of epidemic and nonepidemic strains of Clostridium difficile in murine cecal contents. Stool concentrations of VRE and ceftriaxone were measured, cecal levels of C. difficile 24 h after incubation were quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The results demonstrated that establishment of prior colonization with a ␤-lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone during treatment with this antibiotic, allowed recovery of the normal microbiota despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and nonepidemic strains of C. difficile in mice. These findings describe a novel probiotic strategy to potentially prevent pathogen colonization in hospitalized patients.

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“…With mucosal thinning and/or microperforation of the colonic diverticulum, microorganisms in the gastrointestinal tract can easily transmigrate into the peritoneal space. The other potential risk factor for PDrelated peritonitis is acid suppressive therapy, as several recent studies have shown that a higher pH in the gastrointestinal tract induced by gastric acid suppressants provides a good environment for microbial proliferation and overgrowth [6][7][8][9] . Although these studies showed an association between acid suppression treatment and PD peritonitis, the results remain controversial [9][10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

Kwon

Koh

Chun

et al. 2014

WJG

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AIM:To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS:This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS:Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION:The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Proton pump inhibitors; Histamine 2 receptor antagonists; Gastrointestinal motility; Peritoneal dialysis; PeritonitisCore tip: Bacterial overgrowth/proliferation in an intraluminal environment with a high pH is a well-recognized mechanism for peritonitis development, especially in liver cirrhosis patients. Several studies have investigated whether this mechanism causes peritoneal dialysis (PD)-related peritonitis, although conflicting results have been obtained for the association between acid suppressive therapy and PD-related peritonitis. In addition, no study was conducted to evaluate the association between prokinetics and PD-related peritonitis. Therefore, we sought to assess the effect of gastric acid suppressants and prokinetics on PD-related peritonitis. In the present study, H2B use, but not proton pump inhibitor use, was identified as an independent risk factor for PD-related peritonitis development. RETROSPECTIVE STUDYKwon JE, Koh SJ, Chun J, Kim JW, Kim BG, Lee KL, Im JP, Kim JS, Jung HC. Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis. World J Gastroenterol 2014; 20(25): 8187-8194 Available from: URL:

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Suppression of Gastric Acid Production by Proton Pump Inhibitor Treatment Facilitates Colonization of the Large Intestine by Vancomycin-Resistant Enterococcus spp. and Klebsiella pneumoniae in Clindamycin-Treated Mice

Cited by 28 publications

References 21 publications

Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection

Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection

Gastrointestinal Colonization with a Cephalosporinase-Producing Bacteroides Species Preserves Colonization Resistance against Vancomycin-Resistant Enterococcus and Clostridium difficile in Cephalosporin-Treated Mice

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

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