Longitudinal study of the mcr-1 gene prevalence in Spanish food-producing pigs from 1998 to 2021 and its relationship with the use of polymyxins

Abstract

Background Resistance to colistin was an uncommon phenomenon traditionally linked to chromosome point mutations, but since the first description of a plasmid-mediated colistin-resistance in late 2015, transmissible resistance to colistin has become a Public Health concern. Despite colistin is considered as a human last resort antibiotic, it has been commonly used in swine industry to treat post-weaning diarrhoea in piglets. However, the progressively increase of colistin resistance during the last decade led to the Spanish Medicines and Healthcare Products Agency (AEMPS) to launch a strategic and voluntary plan aimed to reduce colistin consumption in pig production. Our longitudinal study (1998–2021) aimed to evaluate the trend of colistin resistance mediated through the mcr-1 mobile gene in Spanish food-producing pig population and compare it with published polymyxin sales data in veterinary medicine to assess their possible relationships. Results The first mcr-1 positive sample was observed in 2004, as all samples from 1998 and 2002 were mcr-1 PCR-negative. We observed a progressive increase of positive samples from 2004 to 2015, when mcr-1 detection reached its maximum peak (33/50; 66%). From 2017 (27/50; 54%) to 2021 (14/81; 17%) the trend became downward, reaching percentages significantly lower than the 2015 peak (p < 0.001). The abundance of mcr-1 gene in PCR-positive samples showed a similar trend reaching the highest levels in 2015 (median: 6.6 × 104mcr-1 copies/mg of faeces), but decreased significantly from 2017 to 2019 (median 2.7 × 104, 1.2 × 103, 4.6 × 102mcr-1 copies/mg of faeces for 2017, 2018 and 2019, respectively), and stabilizing in 2021 (1.6 × 102mcr-1 copies/mg of faeces) with similar values than 2019. Conclusions Our study showed the decreasing trend of colistin resistance associated to mcr-1 gene, after a previous increase from among 2004–2015, since the European Medicines Agency and AEMPS strategies were applied in 2016 to reduce colistin use in animals, suggesting a connection between polymyxin use and colistin resistance. Thus, these plans could have been effective in mcr-1 reduction, reaching lower levels than those detected in samples collected 17 years ago, when resistance to colistin was not yet a major concern.

Mobile colistin resistance (MCR), extended-spectrum beta-lactamase (ESBL) and multidrug resistance monitoring in Escherichia coli (commensal and pathogenic) in pig farming: need of harmonized guidelines and clinical breakpoints

“…We suggest the monitoring of pathogenic (invasive) E. coli in surveillance programs to accurately determine the persistence of colistin resistance. Our findings on the decrease in colistin-resistant mcr-bearing isolates would reinforce the conclusions of longitudinal studies on the mcr-1 abundance in food-producing pigs, and its relationship with the use of polymyxins (Wang et al, 2020;Miguela-Villoldo et al, 2022). Thus, Miguela-Villoldo et al (2022) reported the decreasing trend of colistin resistance associated with mcr-1 gene in Spain, since the EMA and AEMPS strategies were applied in 2016 to reduce colistin use in animals.…”

“…Our findings on the decrease in colistin-resistant mcr-bearing isolates would reinforce the conclusions of longitudinal studies on the mcr-1 abundance in food-producing pigs, and its relationship with the use of polymyxins (Wang et al, 2020;Miguela-Villoldo et al, 2022). Thus, Miguela-Villoldo et al (2022) reported the decreasing trend of colistin resistance associated with mcr-1 gene in Spain, since the EMA and AEMPS strategies were applied in 2016 to reduce colistin use in animals. Likewise, Wang et al, 2020 showed a substantial reduction in sales of colistin in animals (2015)(2016)(2017)(2018), after the withdrawal of colistin as growth promoter in China in 2017, which was rapidly followed by a significant reduction in the prevalence of mcr-1 in both the animal and human sectors.…”

Occurrence of mcr-1 and mcr-2 colistin resistance genes in porcine Escherichia coli isolates (2010–2020) and genomic characterization of mcr-2-positive E. coli

“…Similar results were reported from Spain. Miguela-Villoldo et al described a steady increase of mcr-1 in bacteria from cecal samples from pigs between 2004 and 2015 and a downward trend between 2017 and 10.3389/fmicb.2022.1076315 (Miguela-Villoldo et al, 2022. Another group from Spain screened 200 E. coli isolates collected in 1999 to 2018 from swine and reported a peak of colistin resistance (17.5% of the strains) in 2011-2014 (Aguirre et al, 2020).…”

Salmonella Shedding in Slaughter Pigs and the Use of Esterified Formic Acid in the Drinking Water as a Potential Abattoir-Based Mitigation Measure

“…Resistance to colistin has been usually low in Spain, even when this drug was used massively in the pig sector [44,47]. The application of the Spanish Plan against Antibiotic Resistance in 2015, and the subsequent reduction in colistin consumption by more than 95% [48], may have contributed to an overall reduction in the detection of the mcr-1 gene [49,50], explaining the absence of phenotypic resistance against colistin in these isolates. Regarding AMR to third-generation cephalosporins, this was found in 5% of the Salmonella isolates.…”