Use of Colistin and Other Critical Antimicrobials on Pig and Chicken Farms in Southern Vietnam and Its Association with Resistance in Commensal Escherichia coli Bacteria

Abstract

Antimicrobial resistance (AMR) is a global health problem, and emerging semi-intensive farming systems in Southeast Asia are major contributors to the AMR burden. We accessed 12 pig and chicken farms at key stages of production in Tien Giang Province, Vietnam, to measure antimicrobial usage and to investigate the prevalence of AMR to five critical antimicrobials (β-lactams, third-generation cephalosporins, quinolones, aminoglycosides, and polymyxins) and their corresponding molecular mechanisms among 180 Escherichia coli isolates. Overall, 94.7 mg (interquartile range [IQR], 65.3 to 151.1) and 563.6 mg (IQR, 398.9 to 943.6) of antimicrobials was used to produce 1 kg (live weight) of chicken and pig, respectively. A median of 3 (out of 8) critical antimicrobials were used on pig farms. E. coli isolates exhibited a high prevalence of resistance to ampicillin (97.8% and 94.4% for chickens and pigs, respectively), ciprofloxacin (73.3% and 21.1%), gentamicin (42.2% and 35.6%), and colistin (22.2% and 24.4%). The prevalence of a recently discovered colistin resistance gene, mcr-1, was 19 to 22% and had strong agreement with phenotypic colistin resistance. We conducted plasmid conjugation experiments with 37 mcr-1 gene-positive E. coli isolates and successfully observed transfer of the gene in 54.0% of isolates through a plasmid of approximately 63 kb, consistent with one recently identified in China. We found no significant correlation between total use of antimicrobials at the farm level and AMR. These data provide additional insight into the role of mcr-1 in colistin resistance on farms and outline the dynamics of phenotypic and genotypic AMR in semi-intensive farming systems in Vietnam.IMPORTANCE Our study provides accurate baseline information on levels of antimicrobial use, as well as on the dynamics of phenotypic and genotypic resistance for antimicrobials of critical importance among E. coli over the different stages of production in emerging pig and poultry production systems in Vietnam. E. coli isolates showed a high prevalence of resistance (>20%) to critically important antimicrobials, such as colistin, ciprofloxacin, and gentamicin. The underlying genetic mechanisms identified for colistin (the mcr-1 gene) and quinolone (gyrA gene mutations) are likely to play a major role in AMR to those compounds. Conjugation experiments led to the identification of a 63-kb plasmid, similar to one recently identified in China, as the potential carrier of the mcr-1 gene. These results should encourage greater restrictions of such antimicrobials in Southeast Asian farming systems.

Antimicrobial Usage and Antimicrobial Resistance in Animal Production in Southeast Asia: A Review

“…Six publications [15,16,17,18,19,20] reported AMU in terrestrial animal production (pigs and chickens), and two in aquaculture production [21,22]. Except for one publication that investigated antimicrobial use to raise chickens in integrated fish–chicken farms [21] in Thailand, and another one that investigated fish and shrimp farms in both Thailand and Vietnam [22], the remaining publications investigated AMU exclusively in Vietnamese farms.…”

“…All studies report types and classes of antimicrobials used on farms over a specified period of time. In three publications (two of which relate to the same study farms), quantitative data are also presented [16,18,23]. In two of these studies [16,18] consumption is presented in terms of grams of antimicrobial compound to produce one kilogram of chicken or pig produced, whereas in the other [23], consumption for chickens was expressed as “treatment incidence” [24].…”

Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia

“…The gene is also present in Enterobacteriaceae from food animals in Vietnam (155,156), with up to 22% of E. coli isolates from 6 each of pig and chicken farms testing positive in a study conducted between 2013 and 2014 (155). Other countries of Southeast Asia.…”

Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives

“…In pigs, the mcr-1 gene was isolated mainly from colistin resistant E. coli strains with variable prevalence between countries; China (20.6%), Vietnam (22%), Belgium (13.2%), Brazil (2%), Spain (0.68%), Germany (0.51%), and France (0.50%) (Falgenhauer et al, 2016; Fernandes et al, 2016; Liu et al, 2016; Malhotra-Kumar et al, 2016a; Nguyen et al, 2016; Perrin-Guyomard et al, 2016; Quesada et al, 2016). Most recently, in the USA pig production, the mcr-1 gene was identified for the first time in a colistin resistant E. coli strain isolated from a pig from South Carolina (Meinersmann et al, 2016).…”

“…Almost all studies conducted on pigs worldwide to screen mcr-1 gene presence in enterobacterial species reported that colistin resistant strains harboring this gene also showed resistance to one or several classes of antibiotics conventionally used in swine such as: Aminoglycoside, Sulfonamide, Trimethoprim, Tetracycline, Quinolone, Lincosamide, β-lactam, and third generation cephalosporin (Anjum et al, 2016; Falgenhauer et al, 2016; Malhotra-Kumar et al, 2016b; Nguyen et al, 2016). This multi-resistance of mcr-1 positive E. coli strains in pigs was associated with the presence of a sul3 -containing class 1 integron, In 640 , in the plasmid’s mediated mcr-1 gene.…”