Guideline implementation is effective at reducing proton pump inhibitor use in hematology-oncology units: A multidisciplinary intervention for reducing Clostridioides difficile risk.
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ABSTRACT:
SUBMITTER: Ziegler MJ
PROVIDER: S-EPMC6893867 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Guideline implementation is effective at reducing proton pump inhibitor use in hematology-oncology units: A multidisciplinary intervention for reducing <i>Clostridioides difficile</i> risk.
Ziegler Matthew J MJ Freyer Craig C Landsburg Daniel D Pegues David D Bilker Warren W Hirsh Rebecca R Kucharczuk Colleen C Gilmar Cheryl C Gorman Theresa T Palmer Melissa M Harker Christina C Lightheart Erin E Han Jennifer H JH
Infection control and hospital epidemiology 20190830 11
We implemented a guideline for appropriate acid suppressant use in hematology-oncology patients. This intervention resulted in a sustained reduction in proton pump inhibitor (PPI) use without an increase in rates of gastrointestinal bleeding. Practice guidelines are effective in reducing PPI use, which is associated with risk of Clostridioides difficile infection. ...[more]
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Project description:Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to Clostridioides difficile infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI treatment were gavaged with 40 mg of omeprazole per kg of body weight during a 7-day pretreatment phase, the day of C. difficile challenge, and the following 9 days. We found that mice treated with omeprazole were not colonized by C. difficile When omeprazole treatment was combined with a single clindamycin treatment, one cage of mice remained resistant to C. difficile colonization, while the other cage was colonized. Treating mice with only clindamycin followed by challenge resulted in C. difficile colonization. 16S rRNA gene sequencing analysis revealed that omeprazole had minimal impact on the structure of the murine microbiota throughout the 16 days of omeprazole exposure. These results suggest that omeprazole treatment alone is not sufficient to disrupt microbiota resistance to C. difficile infection in mice that are normally resistant in the absence of antibiotic treatment.IMPORTANCE Antibiotics are the primary risk factor for Clostridioides difficile infections (CDIs), but other factors may also increase a person's risk. In epidemiological studies, proton pump inhibitor (PPI) use has been associated with CDI incidence and recurrence. PPIs have also been associated with alterations in the human intestinal microbiota in observational and interventional studies. We evaluated the effects of the PPI omeprazole on the structure of the murine intestinal microbiota and its ability to disrupt colonization resistance to C. difficile We found omeprazole treatment had minimal impact on the murine fecal microbiota and did not promote C. difficile colonization. Further studies are needed to determine whether other factors contribute to the association between PPIs and CDIs seen in humans or whether aspects of murine physiology may limit its utility to test these types of hypotheses.
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Project description:BackgroundAntibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.ObjectivesTo assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.MethodsPopulation-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.ResultsCompared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.ConclusionRecent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.
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Project description:BackgroundThe key epidemiological drivers of Clostridioides difficile transmission are not well understood. We estimated epidemiological parameters to characterize variation in C. difficile transmission, while accounting for the imperfect nature of surveillance tests.MethodsWe conducted a retrospective analysis of C. difficile surveillance tests for patients admitted to a bone marrow transplant (BMT) unit or a solid tumor unit (STU) in a 565-bed tertiary hospital. We constructed a transmission model for estimating key parameters, including admission prevalence, transmission rate, and duration of colonization to understand the potential variation in C. difficile dynamics between these 2 units.ResultsA combined 2425 patients had 5491 admissions into 1 of the 2 units. A total of 3559 surveillance tests were collected from 1394 patients, with 11% of the surveillance tests being positive for C. difficile. We estimate that the transmission rate in the BMT unit was nearly 3-fold higher at 0.29 acquisitions per percentage colonized per 1000 days, compared to our estimate in the STU (0.10). Our model suggests that 20% of individuals admitted into either the STU or BMT unit were colonized with C. difficile at the time of admission. In contrast, the percentage of surveillance tests that were positive within 1 day of admission to either unit for C. difficile was 13.4%, with 15.4% in the STU and 11.6% in the BMT unit.ConclusionsAlthough prevalence was similar between the units, there were important differences in the rates of transmission and clearance. Influential factors may include antimicrobial exposure or other patient-care factors.
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Project description:Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Infection of the gastrointestinal tract with this Gram-positive, obligate anaerobe can lead to potentially life-threatening conditions in the antibiotic-treated populace. New therapeutics are urgently needed to treat this infection and prevent its recurrence. Here, we screened two libraries from the National Cancer Institute, namely, the natural product set III library (117 compounds) and the approved oncology drugs set V library (114 compounds), against C. difficile. In the two libraries screened, 17 compounds from the natural product set III library and 7 compounds from the approved oncology drugs set V library were found to exhibit anticlostridial activity. The most potent FDA-approved drugs (mitomycin C and mithramycin A) and a promising natural product (aureomycin) were further screened against 20 clinical isolates of C. difficile. The anticancer drugs, mitomycin C (MIC50?=?0.25 ?g/ml) and mithramycin A (MIC50?=?0.015 ?g/ml), and the naturally derived tetracycline derivative, aureomycin (MIC50?=?0.06 ?g/ml), exhibited potent activity against C. difficile strains. Mithramycin A and aureomycin were further found to inhibit toxin production by this pathogen. Given their efficacy, these compounds can provide a quick supplement to current treatment to address the unmet needs in treating C. difficile infection and preventing its recurrence.
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