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. bla _CTX-M were the most common 3GC resistance genes globally, with the exception of North America where bla _CMY were the predominant 3GC resistance genes. There was not a single dominant bla _CTX-M gene subtype globally and several bla _CTX-M subtypes were dominant depending on the continent. A wide variety of carbapenem-resistance genes (bla _{NDM-, VIM-, IMP-, OXA-48}, _{and KPC-}) 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.

Keywords: ESBL; Escherichia coli; ampC; antimicrobial resistance; carbapenem; cephalosporin; pigs; systematic review.

FIGURE 1

Flowchart describing selection of articles included in this review.

FIGURE 2

Global distribution of sampling indices (number of isolates characterized for phenotypic resistance per 1,000 pigs). “No data” implies that there were no isolates of interest reported and does not mean that there were no pigs in particular countries.

FIGURE 3

Global distribution of pooled proportion estimates of third generation cephalosporin resistance in E. coli isolates collected from healthy pigs. “No data” implies that there were no isolates of interest reported and does not mean that there were no pigs in particular countries.

FIGURE 4

Global distribution of pooled proportion estimates of third generation cephalosporin resistance in E. coli isolates collected from diseased pigs. “No data” implies that there were no isolates of interest reported and does not mean that there were no pigs in particular countries.

FIGURE 5

Global distribution of fecal carriage rates (animal-level prevalence) of third generation cephalosporin resistant E. coli isolates in pigs. “No data” implies that there were no isolates of interest reported and does not mean that there were no pigs in particular countries.

FIGURE 6

Abundances of (A) bla_CTX–M, bla_CMY, and bla_SHV genes and (B) bla_CTX–M groups in ESBL/ampC or 3rd generation cephalosporin resistant E. coli isolates based on the literature review.

FIGURE 7

Relative abundances of (A) bla_CTX–M, bla_CMY, and bla_SHV genes and (B) bla_CTX–M subtypes in publicly available E. coli genomes of swine origin.

FIGURE 8

Top ten variables of importance predictive of (A) bla_CMY and of (B) bla_CTX–M genes in publicly available E. coli genomes of swine origin. Variable importance was estimated using Random Forest models. The numbers on the right side of the bars represent unadjusted odds ratio (95% confidence values). “Blue” and “red” colored bars represent positive (odds ratio > 1) and negative (odds ratio < 1) association between dependent and independent variables.