The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients

被引:2
作者
MacDonald, Tamara [1 ,2 ]
Dunn, Katherine A. [3 ,4 ,5 ]
MacDonald, Jane [3 ,6 ]
Langille, Morgan G. I. [7 ]
Van Limbergen, Johan E. [8 ,9 ]
Bielawski, Joseph P. [4 ,5 ,10 ]
Kulkarni, Ketan [3 ]
机构
[1] IWK Hlth, Dept Pharm, Halifax, NS, Canada
[2] Dalhousie Univ, Fac Hlth Profess, Halifax, NS, Canada
[3] Izaak Walton Killam IWK Hlth, Dept Pediat, Div Hematol Oncol, Halifax, NS, Canada
[4] Dalhousie Univ, Dept Biol, Halifax, NS, Canada
[5] Dalhousie Univ, Inst Comparat Genom, Halifax, NS, Canada
[6] Univ Waterloo, Dept Sci, Waterloo, ON, Canada
[7] Dalhousie Univ, Fac Med, Dept Pharmacol, Halifax, NS, Canada
[8] Univ Amsterdam, Emma Childrens Hosp, Dept Pediat Gastroenterol & Nutr, Med Ctr, Amsterdam, Netherlands
[9] Univ Amsterdam, Med Ctr, Tytgat Inst Liver & Intestinal Res, Amsterdam Gastroenterol Endocrinol & Metab, Amsterdam, Netherlands
[10] Dalhousie Univ, Dept Math & Stat, Halifax, NS, Canada
来源
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2023年 / 13卷
关键词
antibiotic resistance genes; resistome; leukemia; lymphoma; pediatric; microbiome; ACUTE LYMPHOBLASTIC-LEUKEMIA; EFFLUX PUMPS; ANTIMICROBIAL RESISTANCE; MULTIDRUG-RESISTANCE; GUT MICROBIOTA; CHEMOTHERAPY; VIRULENCE; CHILDREN; MICROFLORA; MECHANISMS;
D O I
10.3389/fcimb.2023.1102501
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IntroductionMost children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include beta-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. MethodsWe 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 beta-lactams, vancomycin and "any antibiotic" use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. ResultsWe found that Bacteroidetes taxa and beta-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 beta-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. ConclusionsGiven 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.
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