Abstract
The dynamics of antimicrobial resistance (AMR) in developing countries are poorly understood, especially in community settings, due to a sparsity of data on AMR prevalence and genetics. We used a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenic Escherichia coli (aEPEC) strains isolated from children younger than five years old in seven developing countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected high rates of AMR, with 65% of isolates displaying resistance to three or more drug classes. Whole-genome sequencing revealed a diversity of known genetic mechanisms for AMR that accounted for >95% of phenotypic resistance, with comparable rates amongst aEPEC strains associated with diarrhoea or asymptomatic carriage. Genetic determinants of AMR were associated with the geographic location of isolates, not E. coli lineage, and AMR genes were frequently co-located, potentially enabling the acquisition of multi-drug resistance in a single step. Comparison of AMR with antimicrobial usage data showed that the prevalence of resistance to fluoroquinolones and third-generation cephalosporins was correlated with usage, which was higher in South Asia than in Africa. This study provides much-needed insights into the frequency and mechanisms of AMR in intestinal E. coli in children living in community settings in developing countries.
Highlights
Certain pathotypes of Escherichia coli are important causes of diarrhoea in children, especially in the developing countries of sub-Saharan Africa and South Asia[1]
Enhancing our knowledge of antimicrobial resistance (AMR) amongst gut-dwelling E. coli is important for two reasons: (1) E. coli is a leading cause of extra-intestinal infections and strains colonising the gastrointestinal tract of patients are the major reservoir of these infections; and (2) most AMR in E. coli is encoded on mobile genetic elements that are transferable between bacteria, enabling the rapid dissemination and maintenance of resistance genes between bacteria of different species[23,24]
Antimicrobials are not recommended for the treatment of uncomplicated gastroenteritis, they are commonly administered to diarrhoeic children in developing countries to treat dysentery[25] and prolonged diarrhoea, of which atypical enteropathogenic Escherichia coli (aEPEC) is a major cause[4,5]
Summary
Certain pathotypes of Escherichia coli are important causes of diarrhoea in children, especially in the developing countries of sub-Saharan Africa and South Asia[1]. Several recent studies of pathogenic E. coli from countries in sub-Saharan Africa and South Asia have reported increases in ESBLs15,16, as well as increasing resistance to gentamicin[17,18] and ciprofloxacin[18,19,20,21,22], these data are mostly derived from E. coli responsible for extra-intestinal infections in hospital settings. Using phenotypic susceptibility data and whole-genome sequence analysis, we determined the prevalence, mechanisms of resistance and potential drivers of variation in AMR profiles These isolates, collected from healthy children living in a community setting and children with diarrhoea at seven sites in sub-Saharan Africa and South Asia, provided a unique opportunity to investigate the prevalence of AMR in intestinal bacteria that were not selected on the basis of AMR profile
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