Protecting the Microbiota

Rooney, Christopher; Ahmed, Shadia; Wilcox, Mark H.

doi:10.1093/infdis/jiab143

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…[12,13] In our study, the distribution of Gram-negative bacteria by years was examined, but advanced methods and metataxonomic analyzes could not examine the gut microbiota profile. Due to the increasing associations between an impaired microbiota and susceptibility to infectious disease, research has been directed toward new approaches that protect the microbiota while eliminating pathogens, in particular [14] and new possibilities and treatment modalities have been produced in which wholesale replacement of the microbiota can be used as a highly effective treatment.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

İrvem

2023

Comprehensive Med

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Objective: Antibiotics resistance in bacteria is an important public health problem recently. Resistance rates vary from country to country, from region to region, and even from hospital to hospital. Recently, tigecycline and colistin have been widely used due to increasing multi-resistance in Gram-negative bacteria. The aim of the study was to investigate the changes in colistin and tigecycline intrinsic-resistant bacteria ratio and the effects of these drugs on the hospital flora throughout the hospital due to the widespread use of these drugs. Materials and Methods:In our microbiology laboratory, clinical samples were processed according to the general microbiology procedure. Bacterial identification and antibiogram susceptibility tests were performed with VITEK®2 Compact, MALDI-TOF mass spectrometry (bioMérieux, France). Results were evaluated according to CLSI and EUCAST criteria. The data were scanned retrospectively between the years 2012 and 2019. Chi-square test was used in statistical analysis. Significance was evaluated at the p<0.05 level.Results: While the number of Escherichia coli isolates decreased over the years, an increase was detected in Klebsiella spp. tigecycline intrinsic-resistant bacteria, Proteus spp., Providencia spp., and Pseudomonas spp. When evaluated with the general number of bacteria isolated over the years, Pseudomonas spp., a three-fold increase was found in 2018 and 2019 and in colistin intrinsic-resistant bacteria, Morganella spp., Proteus spp., Providencia spp., Yersinia spp., Burkholderia spp., and Eliseabethkingea spp. No statistically significant increase was detected. A significant increase was detected in Serratia spp. Conclusion:Changes were detected in intrinsic-resistant bacteria and in antibiotic distribution. The antibiotic drugs used affect the entire flora, including the microbiota. The importance of patient care and antibiotic management should be emphasized, targeted therapies treatments should be made that the microbiota will not change, or fecal transplantation methods, which are new methods to replace microbiota, should be investigated.

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Section: Discussionmentioning

confidence: 99%

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

İrvem

2023

Comprehensive Med

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“…Cholestyramine is one of several adjunctive therapies in development that could prevent off-target resistance emergence in the gut during antibiotic treatment [26][27][28][29]. These treatments rely on antibiotic antagonists, which bind to or inactivate antibiotics locally in the intestines.…”

Section: Discussionmentioning

confidence: 99%

Oral cholestyramine prevents enrichment of diverse daptomycin-resistance mutations in intestinal Enterococcus faecium

Morley

Sim

Penkevich

et al. 2022

Preprint

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Background and ObjectivesPreviously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant Enterococcus faecium in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: 1) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging de novo in the gut? 2) how does the timing of cholestyramine administration impact its ability to suppress resistance?MethodologyMice with GI E. faecium were treated with daptomycin with or without cholestyramine, and E. faecium was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance.ResultsCholestyramine prevented the enrichment of diverse resistance mutations that emerged de novo in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the clsA gene. Additionally, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant E. faecium compared to not using cholestyramine at all.Conclusions and ImplicationsCholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal E. faecium populations during daptomycin treatment, and it is a promising tool for managing transmission of daptomycin-resistant E. faecium.

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“…Cholestyramine is one of several adjunctive therapies in development that could prevent off-target resistance emergence in the gut during antibiotic treatment [ 26–29 ]. These treatments rely on antibiotic antagonists, which bind to or inactivate antibiotics locally in the intestines.…”

Section: Discussionmentioning

confidence: 99%

An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy

Morley

Sim

Penkevich

et al. 2022

Evolution, Medicine, and Public Health

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Background and Objectives Previously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant Enterococcus faecium in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: 1) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging de novo in the gut? 2) how does the timing of cholestyramine administration impact its ability to suppress resistance? Methodology Mice with GI E. faecium were treated with daptomycin with or without cholestyramine, and E. faecium was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance. Results Cholestyramine prevented the enrichment of diverse resistance mutations that emerged de novo in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the clsA gene. Additionally, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant E. faecium compared to not using cholestyramine at all. Conclusions and Implications Cholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal E. faecium populations during daptomycin treatment, and it is a promising tool for managing transmission of daptomycin-resistant E. faecium. Lay Summary Antibiotics can select for drug-resistant bacteria in the gut. Here, we demonstrate a strategy for preventing this selection in a mouse model. We show that an orally-administered drug can capture antibiotic in the gut, thus preventing selection for resistance. This strategy allows for antibiotic treatment while reducing transmission of resistance.

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Protecting the Microbiota

Abstract: We examine 3 different approaches to protecting the gut microbiome: highly targeted antibiotics, antibiotic destruction, and antibiotic binding. Each approach shows promise to prevent the off-target effects of antibiotics on the gut microbiome.

Cited by 6 publications

References 37 publications

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

Oral cholestyramine prevents enrichment of diverse daptomycin-resistance mutations in intestinal Enterococcus faecium

An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy

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