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The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients
INTRODUCTION: Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include β-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. METHODS: We examined the impact o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998685/ https://www.ncbi.nlm.nih.gov/pubmed/36909730 http://dx.doi.org/10.3389/fcimb.2023.1102501 |
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author | MacDonald, Tamara Dunn, Katherine A. MacDonald, Jane Langille, Morgan G.I. Van Limbergen, Johan E. Bielawski, Joseph P. Kulkarni, Ketan |
author_facet | MacDonald, Tamara Dunn, Katherine A. MacDonald, Jane Langille, Morgan G.I. Van Limbergen, Johan E. Bielawski, Joseph P. Kulkarni, Ketan |
author_sort | MacDonald, Tamara |
collection | PubMed |
description | INTRODUCTION: Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include β-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. METHODS: We examined the impact of repeated courses and duration of antibiotic use on the resistome of 39 pediatric leukemia and lymphoma patients. Shotgun metagenome sequences from 127 stool samples of pediatric oncology patients were examined for abundance of antibiotic resistance genes (ARGs) in each sample. Abundances were grouped by repeated courses (no antibiotics, 1-2 courses, 3+ courses) and duration (no use, short duration, long and/or mixed durationg) of β-lactams, vancomycin and “any antibiotic” use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. RESULTS: We found that Bacteroidetes taxa and β-lactam resistance genes decreased, while opportunistic Firmicutes and Proteobacteria taxa, along with multidrug resistance genes, increased with repeated courses and/or duration of antibiotics. Efflux pump related genes predominated (92%) among the increased multidrug genes. While we found β-lactam ARGs present in the resistome, the taxa that appear to contain them were kept in check by antibiotic treatment. Multidrug ARGs, mostly efflux pumps or regulators of efflux pump genes, were associated with opportunistic pathogens, and both increased in the resistome with repeated antibiotic use and/or increased duration. CONCLUSIONS: Given the strong association between opportunistic pathogens and multidrug-related efflux pumps, we suggest that drug efflux capacity might allow the opportunistic pathogens to persist or increase despite repeated courses and/or duration of antibiotics. While drug efflux is the most direct explanation, other mechanisms that enhance the ability of opportunistic pathogens to handle environmental stress, or other aspects of the treatment environment, could also contribute to their ability to flourish within the gut during treatment. Persistence of opportunistic pathogens in an already dysbiotic and weakened gastrointestinal tract could increase the likelihood of life-threatening blood borne infections. Of the 39 patients, 59% experienced at least one gastrointestinal or blood infection and 60% of bacteremia’s were bacteria found in stool samples. Antimicrobial stewardship and appropriate use and duration of antibiotics could help reduce morbidity and mortality in this vulnerable population. |
format | Online Article Text |
id | pubmed-9998685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99986852023-03-11 The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients MacDonald, Tamara Dunn, Katherine A. MacDonald, Jane Langille, Morgan G.I. Van Limbergen, Johan E. Bielawski, Joseph P. Kulkarni, Ketan Front Cell Infect Microbiol Cellular and Infection Microbiology INTRODUCTION: Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include β-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. METHODS: We examined the impact of repeated courses and duration of antibiotic use on the resistome of 39 pediatric leukemia and lymphoma patients. Shotgun metagenome sequences from 127 stool samples of pediatric oncology patients were examined for abundance of antibiotic resistance genes (ARGs) in each sample. Abundances were grouped by repeated courses (no antibiotics, 1-2 courses, 3+ courses) and duration (no use, short duration, long and/or mixed durationg) of β-lactams, vancomycin and “any antibiotic” use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. RESULTS: We found that Bacteroidetes taxa and β-lactam resistance genes decreased, while opportunistic Firmicutes and Proteobacteria taxa, along with multidrug resistance genes, increased with repeated courses and/or duration of antibiotics. Efflux pump related genes predominated (92%) among the increased multidrug genes. While we found β-lactam ARGs present in the resistome, the taxa that appear to contain them were kept in check by antibiotic treatment. Multidrug ARGs, mostly efflux pumps or regulators of efflux pump genes, were associated with opportunistic pathogens, and both increased in the resistome with repeated antibiotic use and/or increased duration. CONCLUSIONS: Given the strong association between opportunistic pathogens and multidrug-related efflux pumps, we suggest that drug efflux capacity might allow the opportunistic pathogens to persist or increase despite repeated courses and/or duration of antibiotics. While drug efflux is the most direct explanation, other mechanisms that enhance the ability of opportunistic pathogens to handle environmental stress, or other aspects of the treatment environment, could also contribute to their ability to flourish within the gut during treatment. Persistence of opportunistic pathogens in an already dysbiotic and weakened gastrointestinal tract could increase the likelihood of life-threatening blood borne infections. Of the 39 patients, 59% experienced at least one gastrointestinal or blood infection and 60% of bacteremia’s were bacteria found in stool samples. Antimicrobial stewardship and appropriate use and duration of antibiotics could help reduce morbidity and mortality in this vulnerable population. Frontiers Media S.A. 2023-02-24 /pmc/articles/PMC9998685/ /pubmed/36909730 http://dx.doi.org/10.3389/fcimb.2023.1102501 Text en Copyright © 2023 MacDonald, Dunn, MacDonald, Langille, Van Limbergen, Bielawski and Kulkarni https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology MacDonald, Tamara Dunn, Katherine A. MacDonald, Jane Langille, Morgan G.I. Van Limbergen, Johan E. Bielawski, Joseph P. Kulkarni, Ketan The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title | The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title_full | The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title_fullStr | The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title_full_unstemmed | The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title_short | The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
title_sort | gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998685/ https://www.ncbi.nlm.nih.gov/pubmed/36909730 http://dx.doi.org/10.3389/fcimb.2023.1102501 |
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