The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries

Gompel, Liese Van; Luiken, Roosmarijn E C; Sarrazin, Steven; Munk, Patrick; Knudsen, Berith Elkær; Hansen, Rasmus Borup; Bossers, Alex; Aarestrup, Frank Møller; Dewulf, Jeroen; Wagenaar, Jaap A.; Mevius, Dik; Schmitt, Heike; Heederik, Dick; Dorado-García, Alejandro; Smit, Lidwien A M

doi:10.1093/jac/dky518

Cited by 64 publications

(76 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we anticipated that AMR gene abundance would be inversely related to faecal microbiome diversity. Whilst large cross-sectional studies have been instrumental in furthering our understanding of AMR gene abundance and diversity across different livestock systems 12,21,35 , they have not provided the granularity of data and medicines usage history required to test these hypotheses. For this reason, we chose to undertake a longitudinal dissection of a single commercial pig unit, which included three group in-feed antibiotic treatment regimens and a partial depopulation event.…”

Section: Discussionmentioning

confidence: 99%

“…A previous cross-sectional study highlighted that only 10-42% of the variation in AMR gene levels could be explained by factors included in statistical models (including lifetime antimicrobial exposure), suggesting that AMR gene levels are strongly influenced by a variety of other elements 43 . Whilst these could be related to feed changes, the fact that the dry sows and young pigs were housed differently and fed different diets 44 would suggest that this effect is due to some other factors affecting the entire farm, such as housing and management 35,45,46 , environmental conditions 46 or the introduction of an infectious agent.…”

Section: Changes In Amr Gene Abundances Were Not Associated With Antimentioning

confidence: 99%

See 1 more Smart Citation

Resistance to change: AMR gene dynamics on a commercial pig farm with high antimicrobial usage

Pollock

Muwonge

Hutchings

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Group antimicrobial administration is used to control disease in livestock, but we have little insight into how this impacts antimicrobial resistance (AMR) gene dynamics. Here, a longitudinal study was carried out during a single production cycle on a commercial pig unit with high historic and current antimicrobial usage. Quantitative PCR, 16S rRNA gene metabarcoding and shotgun metagenomic sequencing were used to track faecal AMR gene abundance and diversity and microbiome alpha diversity. Shotgun metagenomic sequencing identified 144 AMR genes in total, with higher AMR gene diversity present in young pigs compared to dry sows. Irrespective of in-feed antibiotic treatment or changes in microbiome diversity, mean AMR gene copy number was consistently high, with some AMR genes present at copy numbers comparable to the bacterial 16S rRNA gene. In conclusion, AMR gene prevalence and abundance were not influenced by antibiotic use, either during the production cycle or following whole-herd medication. The high levels of certain genes indicate they are widely disseminated throughout the microbial population, potentially aiding stability. Despite the high and relatively stable levels of resistance genes against the main antimicrobials used, these compounds continue to control production limiting diseases on this unit.Antimicrobial agents are used regularly in many agricultural systems worldwide to improve the health, welfare and productivity of livestock 1,2 . This has led to concerns about the anthropogenic selection of antimicrobial-resistant bacteria in livestock systems 2-4 , particularly due to the potential transfer of antimicrobial resistance (AMR) genes from livestock to humans 5-7 and into the environment 8,9 . In the United Kingdom, 52% of all antimicrobials sold for livestock were used in the pig and poultry sectors, with tetracyclines being reported as the highest sold antibiotic class 10 . Given the substantial use of antimicrobials in pig production, the association between antimicrobial use and AMR has been an area of intensive study. Specifically, antimicrobial administration has been associated with increased AMR in sentinel bacteria such as Escherichia coli [11][12][13] , Staphylococcus aureus 14,15 , and Campylobacter 16 , Salmonella 17 and Enterococcus 18 species. Molecular studies have revealed a higher richness and diversity of AMR genes in pigs administered oxytetracycline in-feed 19 , with farm origin being associated with AMR gene abundances in faeces at slaughter using both quantitative PCR 20 and metagenomic 21 datasets. However, there are currently few longitudinal studies of AMR in livestock systems, specifically for pig production 22 , with information on antimicrobial use in these systems often derived from national figures, rather than from farm medicines records 12,21 .Here, we examine microbial population dynamics and both AMR gene abundance and diversity on a single pig farm during a six-month production cycle. Faecal samples were collected weekly from a batch of young pigs that were ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Changes In Amr Gene Abundances Were Not Associated With Antimentioning

confidence: 99%

Resistance to change: AMR gene dynamics on a commercial pig farm with high antimicrobial usage

Pollock

Muwonge

Hutchings

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In general, under field conditions, in livestock, the association between AMU and AMR is difficult to assess because additional factors such as vaccination, feed supplements, hygiene conditions and management characteristics also have an impact [11]. In a European study, farm-specific faecal antimicrobial resistomes defined in a metagenomic approach revealed a clear association between usage of tetracyclines and macrolides with the respective resistance genes, while for other widely used substances, no associations were found [12]. In a longitudinal study on one pig farm, the elimination of E. coli carrying the mobile mcr-1 gene coding for colistin resistance was achieved within a 20-month period after stopping colistin treatment [13].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic antimicrobial resistance in Escherichia coli strains isolated from swine husbandries in North Western Germany – temporal patterns in samples from laboratory practice from 2006 to 2017

et al. 2020

View full text Add to dashboard Cite

Background: Since 2011, antibiotic usage has decreased continuously in livestock in Germany. Whether this is accompanied by a reduction in bacterial antimicrobial resistance has not been proven so far. In this study 3054 Escherichia coli (E. coli) isolates from pigs which had suffered from disease on 2161 farms in North Western Germany were evaluated retrospectively from 2006 to 2017 for trends in their antimicrobial resistance pattern. Data were substantially related to the "pre-reduction period" and were therefore suggested as a basis for this task. Minimal inhibitory concentrations for selected antimicrobial substances were evaluated for E. coli strains isolated from different organs of diseased swine sampled for routine diagnostic. In total, 81% of E. coli were isolated from faeces or the gastrointestinal tract, 11% from the genito-urinary tract and 8% from other organs. Susceptibility testing and classification of isolates in accordance with clinical cut-offs followed the Clinical and Laboratory Standards Institute (CLSI). If no clinical cut-offs were available for the respective combination of species, substance and organ, other published clinical cut-offs were used.Results: Differences in susceptibility patterns between isolates from the gastrointestinal and genito-urinary tract were found for most substances. Isolates from the genito-urinary tract were less frequently resistant to ampicillin, apramycin, colistin, neomycin, spectinomycin and tetracycline and more frequently resistant to enrofloxacin and florfenicol. A multifactorial logistic regression model revealed time-dependent decreases in frequency of resistant isolates for neomycin, spectinomycin and tetracycline. For colistin, the highest percentage of resistant isolates with 16.0% was found in 2015 followed by a decrease to the level of 2009-2010 in 2017. A decrease in frequencies of ampicillinresistant isolates was dependent on the age-group and time period. Irrespective of the year, less than 15% E. coli isolates were resistant to apramycin, cephalosporins, colistin, enrofloxacin, florfenicol, gentamicin and neomycin. Conclusion: An overall time-dependent decrease in the percentage of resistant E. coli isolates was found for some substances. These data from diseased animals indicate an impact of a general reduction in antibiotic usage on development of bacterial antimicrobial resistance in the field and can support the decision-making of swine practitioners for treatment options in swine.

show abstract

“…Furthermore, we anticipated that AMR gene abundance would be inversely related to faecal microbiome diversity. Whilst large cross-sectional studies have been instrumental in furthering our understanding of AMR gene abundance and diversity across different livestock systems (13, 25, 62), they have not provided the granularity of data and medicines usage history required to test these hypotheses. For this reason, we chose to undertake a prolonged period of intensive sampling on a single large commercial pig unit during three ‘real world’ group in-feed antimicrobial treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

“…A previous cross-sectional study highlighted that only 10-42% of the variation in AMR gene levels could be explained by factors included in statistical models (including lifetime antimicrobial exposure), suggesting that AMR gene levels are strongly influenced by a variety of other elements (16). Whilst these could be related to feed changes, the fact that the sows and piglets were housed differently and fed different diets (66) would suggest that this effect is due to some other factors affecting the entire farm, such as housing and management (62, 67, 68), ambient temperature (68) and/or humidity, changes in water supply or the introduction of an infectious agent.…”

Section: Discussionmentioning

confidence: 99%

Resistance to change? The impact of group medication on AMR gene dynamics during commercial pig production

Pollock

Muwonge

Hutchings

et al. 2019

Preprint

View full text Add to dashboard Cite

The anthropogenic selection of antimicrobial resistance (AMR) genes is under intense scrutiny, particularly in livestock production, where group antimicrobial administration is used to control disease. Whilst large epidemiological studies provide important data on the diversity and distribution of AMR genes, we have little insight into how group antimicrobial administration impacts AMR gene abundance and diversity within a system. Here, faecal microbiome and AMR gene dynamics were tracked for six months through a standard production cycle on a commercial pig unit. Our results demonstrate that specific AMR genes have reached an equilibrium across this farming system to the extent that the levels measured were maintained from suckling through to slaughter, despite increases in microbiome diversity in early development. These levels were not influenced by antibiotic use, either during the production cycle or following whole herd medication. Some AMR genes were found at levels higher than that of the bacterial 16S rRNA gene, indicating widespread distribution across the most common bacterial genera. The targeted AMR genes were also detected in nearby soil samples, several with decreasing abundance with increasing distance from the unit, demonstrating that the farm acts as a point source of AMR gene ‘pollution’. Metagenomic sequencing of a subset of samples identified 144 AMR genes, with higher gene diversity in the piglet samples compared to the sow samples. Critically, despite overwhelming and stable levels of resistance alleles against the main antimicrobials used on this farm, these compounds continue to control the bacterial pathogens responsible for production losses and compromised welfare.ImportanceGroup antibiotic treatment has been used for decades to control bacterial diseases that reduce the productivity and compromise the welfare of livestock. Recent increases in antibiotic resistant infections in humans has resulted in concerns that antibiotic use in livestock may contribute to the development of untreatable bacterial infections in humans. There is however little understanding as to how the genes that bacteria require to become resistant to antibiotics respond during and after group antibiotic treatment of livestock, particularly in systems where high levels of antibiotics have been used for a prolonged period of time. We show that in such a system, levels of specific antibiotic resistance genes are high irrespective of group antibiotic treatments, whilst dramatic reductions in antibiotic use also fail to reduce the levels of these genes. These findings have important implications for public policy relating to the use of antibiotic in livestock farming.

show abstract

The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries

Cited by 64 publications

References 50 publications

Resistance to change: AMR gene dynamics on a commercial pig farm with high antimicrobial usage

Resistance to change: AMR gene dynamics on a commercial pig farm with high antimicrobial usage

Phenotypic antimicrobial resistance in Escherichia coli strains isolated from swine husbandries in North Western Germany – temporal patterns in samples from laboratory practice from 2006 to 2017

Resistance to change? The impact of group medication on AMR gene dynamics during commercial pig production

Contact Info

Product

Resources

About