Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

Willems, Roel P J; Dijk, Karin van; Ket, Hans; Vandenbroucke-Grauls, Christina M. J. E.

doi:10.1001/jamainternmed.2020.0009

Cited by 66 publications

(58 citation statements)

References 64 publications

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“…We noted that more cases received proton pump inhibitor (PPI) therapy prior to initial sampling than controls (Table 2), consistent with prior studies showing that PPI use is a risk factor for VRE colonization (25,26). Despite this difference in treatment, we found no meaningful difference in the community structure of cases and controls on admission (Fig.…”

Section: Figsupporting

confidence: 87%

Gut Microbiota Predict Enterococcus Expansion but Not Vancomycin-Resistant Enterococcus Acquisition

Chanderraj

Brown

Hinkle

et al. 2020

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Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infections and continues to spread despite widespread implementation of pathogen-targeted control guidelines. Commensal gut microbiota provide colonization resistance to VRE, but the role of gut microbiota in VRE acquisition in at-risk patients is unknown. To address this gap in our understanding, we performed a case-control study of gut microbiota in hospitalized patients who did (cases) and did not (controls) acquire VRE. We matched case subjects to control subjects by known risk factors and “time at risk,” defined as the time elapsed between admission until positive VRE screen. We characterized gut bacterial communities using 16S rRNA gene amplicon sequencing of rectal swab specimens. We analyzed 236 samples from 59 matched case-control pairs. At baseline, case and control subjects did not differ in gut microbiota when measured by community diversity (P = 0.33) or composition (P = 0.30). After hospitalization, gut communities of cases and controls differed only in the abundance of the Enterococcus-containing operational taxonomic unit (OTU), with the gut microbiota of case subjects having more of this OTU than time-matched control subjects (P = 0.01). Otherwise, case and control communities after the time at risk did not differ in diversity (P = 0.33) or community structure (P = 0.12). Among patients who became VRE colonized, those having the Blautia-containing OTU on admission had lower Enterococcus relative abundance once colonized (P = 0.004). Our results demonstrate that the 16S profile of the gut microbiome does not predict VRE acquisition in hospitalized patients, likely due to rapid and profound microbiota change. The gut microbiome does not predict VRE acquisition, but it may be associated with Enterococcus expansion, suggesting that these should be considered two distinct processes. IMPORTANCE The Centers for Disease Control and Prevention estimates that VRE causes an estimated 54,000 infections and 539 million dollars in attributable health care costs annually. Despite improvements in hand washing, environmental cleaning, and antibiotic use, VRE is still prevalent in many hospitals. There is a pressing need to better understand the processes by which patients acquire VRE. Multiple lines of evidence suggest that intestinal microbiota may help some patients resist VRE acquisition. In this large case-control study, we compared the 16S profile of intestinal microbiota on admission in patients that did and did not subsequently acquire VRE. The 16S profile did not predict subsequent VRE acquisition, in part due to rapid and dramatic change in the gut microbiome following hospitalization. However, Blautia spp. present on admission predicted decreased Enterococcus abundance after VRE acquisition, and Lactobacillus spp. present on admission predicted Enterococcus dominance after VRE acquisition. Thus, VRE acquisition and domination may be distinct processes.

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Section: Figsupporting

confidence: 87%

Gut Microbiota Predict Enterococcus Expansion but Not Vancomycin-Resistant Enterococcus Acquisition

Chanderraj

Brown

Hinkle

et al. 2020

mSphere

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“…In addition, in our globalized world, there is a substantial risk for the acquisition of ESBL-producing and/or CRE strains during travel to endemic areas, especially if one comes into contact with a hospital environment in these countries [ 21 , 26 , 27 ]. Clinical infections are often preceded by gut colonization by these MDR pathogens: the risk factors associated with the long-term fecal carriage of ESBL- and carbapenemase-producing Klebsiella and E. coli have been investigated previously in many clinical trials (associated with, e.g., travel history, proton pump inhibitor use) [ 21 , 24 , 33 ]. However, only very few studies have analyzed the relationship between the intestinal microbiota composition and carrier status [ 26 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Colonization Dynamics of Multidrug-Resistant Klebsiella pneumoniae Are Dictated by Microbiota-Cluster Group Behavior over Individual Antibiotic Susceptibility: A Metataxonomic Analysis

et al. 2021

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Gastrointestinal carriage of multidrug-resistant (MDR) bacteria is one of the main risk factors for developing serious, difficult-to-treat infections. Given that there is currently no all-round solution to eliminate colonization with MDR bacteria, it is particularly important to understand the dynamic process of colonization to aid the development of novel decolonization strategies. The aim of our present study was to perform metataxonomic analyses of gut microbiota dynamics during colonization with an extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Klebsiella pneumoniae (ECKP) strain in mice; additionally, to ascertain the effects of antibiotic administration (ampicillin, ceftazidime, and ciprofloxacin) on the establishment and elimination of ECKP intestinal colonization. We have found that the phyla Bacteroidetes and Firmicutes were most dominant in all of the treatment groups; however, Bacteroidetes was more common in the groups treated with antibiotics compared to the control group. Significant differences were observed among the different antibiotic-treated groups in beta but not alpha diversity, implying that the difference is the relative abundance of some bacterial community members. Bacteria from the Lachnospiraceae family (including Agathobacter, Anaerostipes, Lachnoclostridium 11308, Lachnospiraceae UCG-004, Lachnospiraceae NK3A20 group 11318, Lachnospiraceae NK4A136 group 11319, Roseburia, and Tyzzerella) showed an inverse relationship with the carriage rate of the ECKP strain, whereas members of Enterobacteriaceae and the ECKP strain have shown a correlational relationship. Our results suggest that the composition of the microbial community plays a primary role in the MDR-colonization rate, whereas the antibiotic susceptibility of individual MDR strains affects this process to a lesser extent. Distinct bacterial families have associated into microbial clusters, collecting taxonomically close species to produce survival benefits in the gut. These associations do not develop at random, as they may be attributed to the presence of specific metabolomic networks. A new concept should be introduced in designing future endeavors for MDR decolonization, supplemented by knowledge of the composition of the host bacterial community and the identification of bacterial clusters capable of suppressing or enhancing the invader species.

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“…PPI use is implicated in altered gut microbiota composition, bacterial colonisation patterns, including multi-drug resistant microorganisms, and increased susceptibility to enteric bacterial infections. 24,25 Although no direct evidence exists, it may be possible that Kp as a major etiological agent of liver abscess 26 , particularly in Asian countries, could be linked to the observation that PPI therapy is associated with an increased risk of cryptogenic liver abscess. 27 The role of NSAIDs as a risk factor is unclear, but NSAID use has been shown to influence the gastrointestinal microbiota towards a higher relative abundance of Enterobacteriaceae .…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population in Norway: a cross-sectional study of risk factors and bacterial genomic diversity

Raffelsberger

Hetland

Svendsen

et al. 2021

Preprint

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Background: Klebsiella pneumoniae is a leading public health threat due to its increasing prevalence of antibiotic resistance. Gastrointestinal carriage of K. pneumoniae is a risk factor for subsequent infections in hospitalised patients. We determined risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonising humans in a representative sample of a general population. Methods: 2,975 individuals (54% women) ≥40y participating in the population-based Tromso Study 7 (2015-2016) were included. Faecal samples were screened for K. pneumoniae which were characterised using whole-genome sequencing. Risk factors for carriage were analysed using data from the Norwegian Prescription Database and questionnaires, using multivariable logistic regression. Findings: Prevalence of K. pneumoniae gastrointestinal carriage was 16.3% (95% CI 15.0-17.7%) with no gender difference. Risk factors associated with carriage included age ≥60y, travel to Greece or Asia past 12 months (adjusted odds ratio 1.49, 95% CI 1.11-2.00), Crohn's disease/ulcerative colitis (2.26, 1.20-4.27), use of protein pump inhibitors (1.62, 1.18-2.22) and non-steroidal anti-inflammatory drugs past six months (1.38, 1.04-1.84), and antibiotic use last month (1.73, 1.05-2.86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Among the isolates, 5.2% and 11.6% harboured acquired resistance and virulence factors, respectively. Interpretation: Identification of risk factors for gastrointestinal carriage in a representative sample of a general population allows for identification of individuals that may have a higher risk of extraintestinal infection during hospitalisation. The diverse population structure of K. pneumoniae carriage isolates reflects the ecologically adaptive capacity of the bacterium, and the low antibacterial consumption probably contributes to the low prevalence of resistance in clinical isolates in Norway.

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Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms

Cited by 66 publications

References 64 publications

Gut Microbiota Predict Enterococcus Expansion but Not Vancomycin-Resistant Enterococcus Acquisition

Gut Microbiota Predict Enterococcus Expansion but Not Vancomycin-Resistant Enterococcus Acquisition

Colonization Dynamics of Multidrug-Resistant Klebsiella pneumoniae Are Dictated by Microbiota-Cluster Group Behavior over Individual Antibiotic Susceptibility: A Metataxonomic Analysis

Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population in Norway: a cross-sectional study of risk factors and bacterial genomic diversity

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