Abstract
BackgroundExtended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. Colonisation prevalence data in Cambodia are lacking. The aim of this study was to determine gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated socio-demographic risk factors; and to characterise relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS).ResultsFaeces and questionnaire data were obtained from individuals < 16 years in north-western Cambodia, 2012. WGS of cultured ESC-R-EC/KP was performed (Illumina). Maximum likelihood phylogenies were used to characterise relatedness of isolates; ESC-R-associated resistance genes and their genetic contexts were identified from de novo assemblies using BLASTn and automated/manual annotation. 82/148 (55%) of children/adolescents were ESC-R-EC/KP colonised; 12/148 (8%) were co-colonised with both species. Independent risk factors for colonisation were hospitalisation (OR: 3.12, 95% CI [1.52–6.38]) and intestinal parasites (OR: 3.11 [1.29–7.51]); school attendance conferred decreased risk (OR: 0.44 [0.21–0.92]. ESC-R strains were diverse; the commonest ESC-R mechanisms were blaCTX-M 1 and 9 sub-family variants. Structures flanking these genes were highly variable, and for blaCTX-M-15, − 55 and − 27 frequently involved IS26. Chromosomal blaCTX-M integration was common in E. coli.ConclusionsGastrointestinal ESC-R-EC/KP colonisation is widespread in Cambodian children/adolescents; hospital admission and intestinal parasites are independent risk factors. The genetic contexts of blaCTX-M are highly mosaic, consistent with rapid horizontal exchange. Chromosomal integration of blaCTX-M may result in stable propagation in these community-associated pathogens.
Highlights
Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia
The gastrointestinal colonisation prevalence of ESCresistant (ESC-R) E. coli and K. pneumoniae in Cambodia has previously only been investigated in hospitalised neonates [13], where on initial admission 21% were colonised with extended-spectrum cephalosporins (ESCs)-R E. coli (ESC-R-EC) and 33% with ESC-R K. pneumoniae (ESC-R-KP), increasing to 34 and 42% respectively on repeat admissions
Culture and basic demographics In total, 196 faecal samples were obtained from a consecutive subset of children/adolescents enrolled in an intestinal parasite prevalence study. 48 samples were excluded from this study because of: (i) lack of specific consent for wider use of the faecal samples beyond the faecal parasite survey (n = 36); (ii) no epidemiological data records (n = 1); (iii) no (n = 3) or poor (n = 5) growth on culture; or (iv) replicate samples for the same patient (n = 3), leaving 148 samples/individuals for analysis
Summary
Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. The aim of this study was to determine gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated socio-demographic risk factors; and to characterise relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS). Escherichia coli and Klebsiella pneumoniae are two bacterial pathogens of the Enterobacteriaceae family that can cause a wide spectrum of clinical disease, ranging from cystitis and intra-abdominal abscesses to sepsis Both species asymptomatically colonise the gastrointestinal tract, a reservoir that assists in the acquisition and spread of antimicrobial resistance (AMR) [1, 2]. Our study aimed to expand on this work by: (i) estimating the prevalence of gastrointestinal colonisation with ESC-R-EC and ESC-R-KP in Cambodian children and adolescents, and the molecular mechanisms responsible; (ii) investigating socio-demographic risk factors for ESC-R colonisation; (iii) determining genetic relatedness of ESC-R strains
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