The cystic fibrosis gut as a potential source of multidrug resistant pathogens.
J Cyst Fibros
; 20(3): 413-420, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33250435
ABSTRACT
BACKGROUND:
The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers.METHODS:
Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phenotypically, and genetic determinants of resistance characterised by whole genome sequencing.RESULTS:
CF and control faecal resistomes differed significantly (P = 0.0003). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF (P = 0.014) and the composition was significantly different (P = 0.0001). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant(6)-Ib, aac(6')-Ip, and aph(3')-IIIa (P < 0.01). Culture-based analysis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria (P < 0.0001). Isolated extended spectrum beta lactamase (ESBL)-positive Escherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic analysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emergence through horizontal gene transfer.CONCLUSIONS:
The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Cística
/
Farmacorresistência Bacteriana
/
Fezes
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Microbioma Gastrointestinal
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Antibacterianos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Cyst Fibros
Ano de publicação:
2021
Tipo de documento:
Article