Global Distribution of Extended Spectrum Cephalosporin and Carbapenem Resistance and Associated Resistance Markers in Escherichia coli of Swine Origin – A Systematic Review and Meta-Analysis

Abstract

Third generation cephalosporins and carbapenems are considered critically important antimicrobials in human medicine. Food animals such as swine can act as reservoirs of antimicrobial resistance (AMR) genes/bacteria resistant to these antimicrobial classes, and potential dissemination of AMR genes or resistant bacteria from pigs to humans is an ongoing public health threat. The objectives of this systematic review and meta-analysis were to: (1) estimate global proportion and animal-level prevalence of swine E. coli phenotypically resistant to third generation cephalosporins (3GCs) and carbapenems at a country level; and (2) measure abundances and global distribution of the genetic mechanisms that confer resistance to these antimicrobial classes in these E. coli isolates. Articles from four databases (CAB Abstracts, PubMed/MEDLINE, PubAg, and Web of Science) were screened to extract relevant data. Overall, proportion of E. coli resistant to 3GCs was lower in Australia, Europe, and North America compared to Asian countries. Globally, <5% of all E. coli were carbapenem-resistant. Fecal carriage rates (animal-level prevalence) were consistently manifold higher as compared to pooled proportion of resistance in E. coli isolates. blaCTX–M were the most common 3GC resistance genes globally, with the exception of North America where blaCMY were the predominant 3GC resistance genes. There was not a single dominant blaCTX–M gene subtype globally and several blaCTX–M subtypes were dominant depending on the continent. A wide variety of carbapenem-resistance genes (blaNDM–, VIM–, IMP–, OXA–48, andKPC–) were identified to be circulating in pig populations globally, albeit at very-low frequencies. However, great statistical heterogeneity and a critical lack of metadata hinders the true estimation of prevalence of phenotypic and genotypic resistance to these antimicrobials. Comparatively frequent occurrence of 3GC resistance and emergence of carbapenem resistance in certain countries underline the urgent need for improved AMR surveillance in swine production systems in these countries.

Genomic epidemiology of third-generation cephalosporin-resistant Escherichia coli from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms

“…In this study, 3GC-R E. coli positivity seen in pigs was typical of what is seen globally ( 11 ). Additionally, we noted that the 3GC-R isolates from pig farms were more likely to carry genes associated with florfenicol and amoxicillin/clavulanate resistance than those from cattle farms.…”

“…Further investigation of this difference is warranted. The prevalence can be compared with similar studies in other countries, though, as has been discussed in a recent systematic review ( 11 ), differences in sampling strategy and selection make comparisons difficult. Key differences include the use of an initial selective enrichment step (not used here) designed to lower the limit of detection, increasing the observed prevalence of resistance by increasing test sensitivity, and the selective antibiotic used [here, we used cefotaxime, which was the most common selective agent in the systematic review of 3GC-R E. coli studies from pig samples globally ( 11 )].…”

Whole Genome Sequencing (WGS) Analysis of Virulence and AMR Genes in Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli from Animal and Environmental Samples in Four Italian Swine Farms

“…Specifically, the qnrS1 gene, confers low level resistance against fluoroquinolones, making more difficult to treat bacterial pathogens carrying this gene [ 21 , 22 ]. The co-resistance to these antibiotic classes can occur in swine ESBL-positive fecal samples [ 23 , 24 ] and it might be linked to the overuse of fluoroquinolones and macrolides to treat animals in Italy [ 25 , 26 ].…”

Development of an In Vivo Extended-Spectrum Cephalosporin-Resistant Escherichia coli Model in Post-Weaned Pigs and Its Use in Assessment of Dietary Interventions

“…Extended-spectrum cephalosporin-resistant E. coli was first detected in food-producing animals in 1996 and despite tightened regulations of ESC usage, has since been detected globally in swine [ 3 , 6 , 7 , 8 ]. This resistance is predominantly attributed to variants of the bla CTX-M and bla CMY genes [ 5 ].…”