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Source: http://www.cidrap.umn.edu/news-pers...ressants-tied-colonization-resistant-bacteria
Acid suppressants tied to colonization with resistant bacteria
Filed Under:
Antimicrobial Stewardship; Clostridium difficile
Chris Dall | News Reporter | CIDRAP News
| Feb 27, 2020
A new analysis of observational studies involving nearly 30,000 patients suggests medications that people take for acid reflux and related stomach problems may increase the risk of colonization with multidrug-resistant organisms (MDROs).
In a systematic review and meta-analysis published this week in JAMA Internal Medicine, researchers from the Netherlands found that gastric acid suppressants—mainly proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2Ras)—were associated with a more than 70% increase in the odds of MDRO colonization of the intestinal tract.
The findings do not prove that acid-suppressing medications cause MDRO colonization, but they add to a growing concern that the widely used—and frequently overprescribed—drugs may affect the composition of intestinal bacteria in potentially harmful ways. Gastric acid suppressants are also associated with increased risk of Clostridioides difficile infection, and previous studies have found links with rectal carriage of antibiotic-resistant bacteria.
[h=3]Significant association found[/h] The review and meta-analysis looked at 26 observational studies published from 1996 through 2019 that involved 29,382 participants, 38.9% of whom were acid suppressant users. The selected studies, which included cohort, case-control, and cross-sectional studies, all investigated the association between acid suppression and risk of intestinal MDRO colonization.
Target pathogens included multidrug-resistant (MDR) Enterobacteriaceae (carrying extended-spectrum beta-lactamases (ESBLs), carbapenemases, and plasmid-mediated AmpC beta-lactamases), vancomycin-resistant enterococci (VRE), and MDR Pseudomonas or Acinetobactor species.
A primary analysis of 12 studies that were adjusted for confounding factors found that the odds ratio (OR) for intestinal colonization with MDR Enterobacteriaceae or VRE among acid suppressant users was 1.74 (95% CI, 1.40 to 2.16). A secondary analysis of all 26 studies produced similar results (OR, 1.70; 95% CI, 1.44 to 1.99). Further analysis based on the type of study design and setting produced similar results.
The analysis also found that the risk of MDRO colonization associated with PPI use (OR, 1.81; 95% CI, 1.52 to 2.16) was larger than the risk associated with H2RAs (OR, 1.33; 95% CI, 0.86 to 2.08), which was not surprising given that PPIs are more potent acid suppressants. But the researchers note that only 4 studies involved H2RA use, while 17 involved PPIs).
[h=3]Possible explanations[/h] While the authors of the paper caution that the findings are observational and patients who use acid suppressing medications may have other risk factors for MDRO colonization, they lay out three explanations for how these drugs could facilitate intestinal MDRO colonization.
One explanation is that the reduction of gastric acid, which kills all organisms that enter the stomach, may enable MDR bacteria to survive and move on to the intestinal tract. Another is that PPIs and H2RAs can alter the composition of the intestinal microbiota in ways that allow for resistant bacteria to take root.
Finally, some MDROs, in particular certain strains of ESBL-producing Escherichia coli, have been found to contain amino acid substitutions that confer resistance to gastric acid.
The authors of the paper say the findings, along with other associated adverse effects observed in other studies, are a reason for clinicians to be cautious with prescribing acid suppressants. They note that 50% to 70% of PPI use has been found to be inappropriate, with patients either not having an identifiable reason for taking them or taking them for much longer than is necessary.
"We advocate that acid suppressants should be used when necessary but that unnecessary use should be avoided," they wrote.
They also suggest that promoting rational use of acid suppressants could interact favorably with infection control and antibiotic stewardship efforts.
In an accompanying commentary, Todd Lee, MD, MPH, and Emily McDonald, MD, of McGill University in Montreal, say the findings provide another reason clinicians should avoid prescribing PPIs to patients who don't need them, and assess whether patients who are taking them long term still need to be taking them.
"For most patients receiving PPIs long term, at least an annual reassessment for an ongoing requirement or benefit is reasonable," they wrote.
See also:
Mar 29, 2017, CIDRAP News story "Heartburn drugs tied to higher risk of recurrent C diff"
Acid suppressants tied to colonization with resistant bacteria
Filed Under:
Antimicrobial Stewardship; Clostridium difficile
Chris Dall | News Reporter | CIDRAP News
| Feb 27, 2020
A new analysis of observational studies involving nearly 30,000 patients suggests medications that people take for acid reflux and related stomach problems may increase the risk of colonization with multidrug-resistant organisms (MDROs).
In a systematic review and meta-analysis published this week in JAMA Internal Medicine, researchers from the Netherlands found that gastric acid suppressants—mainly proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2Ras)—were associated with a more than 70% increase in the odds of MDRO colonization of the intestinal tract.
The findings do not prove that acid-suppressing medications cause MDRO colonization, but they add to a growing concern that the widely used—and frequently overprescribed—drugs may affect the composition of intestinal bacteria in potentially harmful ways. Gastric acid suppressants are also associated with increased risk of Clostridioides difficile infection, and previous studies have found links with rectal carriage of antibiotic-resistant bacteria.
[h=3]Significant association found[/h] The review and meta-analysis looked at 26 observational studies published from 1996 through 2019 that involved 29,382 participants, 38.9% of whom were acid suppressant users. The selected studies, which included cohort, case-control, and cross-sectional studies, all investigated the association between acid suppression and risk of intestinal MDRO colonization.
Target pathogens included multidrug-resistant (MDR) Enterobacteriaceae (carrying extended-spectrum beta-lactamases (ESBLs), carbapenemases, and plasmid-mediated AmpC beta-lactamases), vancomycin-resistant enterococci (VRE), and MDR Pseudomonas or Acinetobactor species.
A primary analysis of 12 studies that were adjusted for confounding factors found that the odds ratio (OR) for intestinal colonization with MDR Enterobacteriaceae or VRE among acid suppressant users was 1.74 (95% CI, 1.40 to 2.16). A secondary analysis of all 26 studies produced similar results (OR, 1.70; 95% CI, 1.44 to 1.99). Further analysis based on the type of study design and setting produced similar results.
The analysis also found that the risk of MDRO colonization associated with PPI use (OR, 1.81; 95% CI, 1.52 to 2.16) was larger than the risk associated with H2RAs (OR, 1.33; 95% CI, 0.86 to 2.08), which was not surprising given that PPIs are more potent acid suppressants. But the researchers note that only 4 studies involved H2RA use, while 17 involved PPIs).
[h=3]Possible explanations[/h] While the authors of the paper caution that the findings are observational and patients who use acid suppressing medications may have other risk factors for MDRO colonization, they lay out three explanations for how these drugs could facilitate intestinal MDRO colonization.
One explanation is that the reduction of gastric acid, which kills all organisms that enter the stomach, may enable MDR bacteria to survive and move on to the intestinal tract. Another is that PPIs and H2RAs can alter the composition of the intestinal microbiota in ways that allow for resistant bacteria to take root.
Finally, some MDROs, in particular certain strains of ESBL-producing Escherichia coli, have been found to contain amino acid substitutions that confer resistance to gastric acid.
The authors of the paper say the findings, along with other associated adverse effects observed in other studies, are a reason for clinicians to be cautious with prescribing acid suppressants. They note that 50% to 70% of PPI use has been found to be inappropriate, with patients either not having an identifiable reason for taking them or taking them for much longer than is necessary.
"We advocate that acid suppressants should be used when necessary but that unnecessary use should be avoided," they wrote.
They also suggest that promoting rational use of acid suppressants could interact favorably with infection control and antibiotic stewardship efforts.
In an accompanying commentary, Todd Lee, MD, MPH, and Emily McDonald, MD, of McGill University in Montreal, say the findings provide another reason clinicians should avoid prescribing PPIs to patients who don't need them, and assess whether patients who are taking them long term still need to be taking them.
"For most patients receiving PPIs long term, at least an annual reassessment for an ongoing requirement or benefit is reasonable," they wrote.
See also:
Mar 29, 2017, CIDRAP News story "Heartburn drugs tied to higher risk of recurrent C diff"