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

Pedro Miguela-Villoldo; Miguel A Moreno; David Rodríguez-Lázaro; Alejandro Gallardo; Marta Hernández; Tania Serrano; José L Sáez; Cristina de Frutos; Montserrat Agüero; Alberto Quesada; Lucas Domínguez; María Ugarte-Ruiz

doi:10.1186/s40813-022-00255-0

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

Porcine Health Manag. 2022 Mar 17;8(1):12. doi: 10.1186/s40813-022-00255-0.

Authors

Pedro Miguela-Villoldo^{1

2}, Miguel A Moreno^{3

4}, David Rodríguez-Lázaro⁵, Alejandro Gallardo⁶, Marta Hernández⁷, Tania Serrano⁸, José L Sáez⁹, Cristina de Frutos¹⁰, Montserrat Agüero¹⁰, Alberto Quesada^{6

11}, Lucas Domínguez^{3

4}, María Ugarte-Ruiz³

Affiliations

¹ VISAVET Health Surveillance Centre, Universidad Complutense de Madrid, Avenida Puerta de Hierro, s/n, 28040, Madrid, Spain. pedromig@ucm.es.
² Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avenida Puerta de Hierro, s/n, 28040, Madrid, Spain. pedromig@ucm.es.
³ VISAVET Health Surveillance Centre, Universidad Complutense de Madrid, Avenida Puerta de Hierro, s/n, 28040, Madrid, Spain.
⁴ Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avenida Puerta de Hierro, s/n, 28040, Madrid, Spain.
⁵ Área de Microbiología, Departamento de Biotecnología y Ciencia de los Alimentos, Universidad de Burgos, Burgos, Spain.
⁶ Departamento de Bioquímica, Biología Molecular y Genética, Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad s/n, 10003, Cáceres, Spain.
⁷ Laboratorio de Biología Molecular y Microbiología, Instituto Tecnológico Agrario de Castilla y León, Valladolid, Spain.
⁸ Tecnologías y Servicios Agrarios S.A, Madrid, Spain.
⁹ Subdirección General de Sanidad e Higiene Animal y Trazabilidad, Ministerio de Agricultura y Pesca, Alimentación y Medio Ambiente, Madrid, Spain.
¹⁰ Laboratorio Central de Veterinaria, Algete, Madrid, Spain.
¹¹ INBIO G+C, Universidad de Extremadura, Avenida de la Universidad s/n, 10003, Cáceres, Spain.

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 × 10⁴ mcr-1 copies/mg of faeces), but decreased significantly from 2017 to 2019 (median 2.7 × 10⁴, 1.2 × 10³, 4.6 × 10² mcr-1 copies/mg of faeces for 2017, 2018 and 2019, respectively), and stabilizing in 2021 (1.6 × 10² mcr-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.

Keywords: Antimicrobial resistance; Colistin; Real-time PCR; Resistance genes; Swine.

Abstract

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