antibiotics – Swine in Minnesota

A new multidrug resistant Salmonella enterica serotype found in Midwestern swine

Text reproduced from the Center for Infectious Disease Research and Policy (CIDRAP)

A new study by Dr. Julio Alvarez‘s team from the STEMMA laboratory, published in Clinical infectious Diseases suggests that a Salmonella strain circulating in pigs in the US Midwest is part of an emerging clade from Europe that is resistant to multiple antibiotics and may pose a public health risk.

The strain, Salmonella 4,[5],12:i:-, causes many foodborne disease outbreaks mostly tied to pigs and pork products and is expanding in the United States, according to the report by researchers from Minnesota and the United Kingdom.

The team used whole-genome sequencing to assess the relatedness of 659 S 4,[5],12:i:- isolates and 325 S Typhimurium isolates from various sources and locations in the United States and Europe. They also searched for resistance genes and other virulence factors and, for 50 livestock isolates and 22 human isolates, determined the antimicrobial resistance phenotypes.

The researchers found that the S 4,[5],12:i:- isolates fell into two main clades, regardless of their host or place of origin. Eighty-four percent of the US isolates recovered from 2014 through 2016, including nearly all those from pigs in the Midwest, were part of an emerging clade. This clade carried multiple genetic markers for antimicrobial resistance, including resistance to ampicillin, streptomycin, sulphonamides, and tetracyclines.

In addition, phenotypic (actual) resistance to enrofloxacin and ceftiofur was found in 11 of the 50 tested livestock isolates and 9 of the 22 human isolates. This was accompanied by plasmid-mediated resistance genes.

The authors conclude that S 4,[5],12:i:- strains circulating in Midwestern swine herds “are likely part of an emerging multidrug resistant clade first reported in Europe, and can carry plasmid-mediated resistance genes that may be transmitted horizontally to other bacteria and thus could represent a public-health concern.”

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Abstract

Background
Salmonella 4,[5],12:i:-, a worldwide emerging pathogen that causes many foodborne outbreaks mostly attributed to pig and pig products, is expanding in the U.S

Methods
Whole genome sequencing was applied to conduct multiple comparisons of 659 S. 4,[5],12:i:- and 325 S. Typhimurium from different sources and locations (i.e. U.S. and Europe) to assess their genetic heterogeneity, with a focus on strains recovered from swine in the U.S. Midwest. In addition, presence of resistance genes and other virulence factors was detected and the antimicrobial resistance phenotype of 50 and 22 isolates of livestock and human origin, respectively, was determined.

Results
The S. 4,5,12:i:- strains formed two main clades regardless of their source and geographical origin. Most (84%) of the U.S. isolates recovered in 2014–2016, including those (50/51) recovered from swine in the U.S. Midwest, were part of an emerging clade. In this clade, multiple genotypic resistance determinants were predominant, including resistance against ampicillin, streptomycin, sulphonamides and tetracyclines (ASSuT). Phenotypic resistance to enrofloxacin (11/50) and ceftiofur (9/50) was found in conjunction with the presence of plasmid-mediated resistance genes (qnrB19/qnrB2/qnrS1 and bla_CMY-2/bla_SHV-12,respectively). Also, higher similarity was found between S. 4,[5],12:i:- from the emerging clade and S. Typhimurium from Europe than with S. Typhimurium from the U.S.

Conclusions
Salmonella 4,[5],12:i:- currently circulating in swine in the U.S. Midwest are likely part of an emerging multidrug resistant clade first reported in Europe, and can carry plasmid-mediated resistance genes that may be transmitted horizontally to other bacteria and thus could represent a public-health concern.

Metabolites, antibiotimicrobials, and gut microbiome

In this article published by the National Hog Farmer, nutritionists and microbiome analysts from the University of Minnesota discuss what consequences antimicrobials can have on the gut microbiome.

What does microbiome mean?

Microbiome refers to all of the microbes present in an area. For example, gut microbiome is the entire population of microorganisms (most of the time bacteria) present in the intestinal tract.

The purpose of this research program is to study the effects antimicrobials can have on the bacterial populations present in the gut and how those changes influence the metabolites present in the pig.

What is a metabolite?

Metabolites are usually small molecules and are created by enzymatic reactions happening through the natural life of a cell or organism.

One of the effects of administering tylosin to pigs was the increased growth of bacteria producing short-chain fatty acids in the intestinal flora. The use of this antimicrobial also led to the development of Lactobacillus in the gut.

Relating changes in metabolites to the gut microbiome allows for a more complete understanding and investigation of the impact that antibiotics have in enhancing growth. Without completely understanding the mechanism of increased growth, antibiotic alternatives could be used inappropriately without much added benefit.

Link to the full paper

What does antimicrobial-resistant bacteria really mean?

Antimicrobial resistance is an expression that everyone in swine production has heard at least once but what does it really mean? How are you as a producer or veterinarian affected?

Villalta NHF antimicrobial resistance 2017.gif

In this column for the National Hog Farmer, Dr. Carles Vilalta explains that beyond the definition of a bacterium that is not affected by an antimicrobial, there are two different approaches to think about resistance:

One is determined by the Minimal Inhibitory Concentration or MIC, which records the minimum medicine concentration required to stop the growth of the bacteria.
The other focuses on the presence of genes enabling the bacterium to counteract the effect of the antimicrobial.

These genes are usually present in a sub-population of bacteria called mutants. The video below created by Harvard Medical School shows how these mutants can develop, adapt, and survive the highest antimicrobial concentrations. (video length < 2min)

Ionophore intoxication in swine

In this month column of the National Hog Farmer, Dr. Albert Rovira from the University of Minnesota is reviewing the cases of intoxication due to ionophores, these antibiotics given through the feed to control bacterial and coccidial infections in swine.Clinical signs are non-specific. Indeed, pigs become weak and stop eating but do not have a fever. In more severe cases, neurological signs can be noted. However, histological lesions are striking with a dramatic change of the muscle structure as is shown in Figure 1 below.

ionophore-intoxication

There are three main causes of ionophore intoxication in swine:

Dosage error in the diet: the optimal concentration is very small, between 15 and 30 parts per milliom.
Mixing ionophore and tiamulin: Tiamulin prevents the ionophore from being excreted by the body, leading to toxic blood levels.
Inclusion of ionophores designed for another species. Usually, the levels are incorporated at a concentration higher than the toxic level.

In conclusion although cases of ionophore intoxication are rare in swine, it may become more prevalent starting in 2017, with the approval of the only swine ionophore as a growth promotant.

Link to the full article

What is the antimicrobial susceptibility of US Brachyspira species?

To answer this question, Drs. Mirajkar, Davies, and Gebhart from the University of Minnesota, collected a total of 124 field isolates originating from all over the country. In this study, four different Brachyspira species were evaluated for their susceptibility against the main antimicrobial medicines used in swine production. Overall the US isolates had the tendency to be less resistant to antimicrobials than were isolates from other countries. However, low susceptibility to lincomycin and to tylosin were noted in the domestic strains. Lastly, the authors raised the question of the lack of Clinical and Laboratory Standards Institute-approved clinical breakpoints for Brachyspira species which, by categorizing an isolate as sensitive, intermediate, or resistant, would be a tremendous help in determining the best treatment and control strategies at the farm level .

Mirajkar antimicrobial susceptibility brachyspira

Abstract: Outbreaks of swine dysentery, caused by Brachyspira hyodysenteriae and the recently discovered “Brachyspira hampsonii,” have reoccurred in North American swine herds since the late 2000s. Additionally, multiple Brachyspira species have been increasingly isolated by North American diagnostic laboratories. In Europe, the reliance on antimicrobial therapy for control of swine dysentery has been followed by reports of antimicrobial resistance over time. The objectives of our study were to determine the antimicrobial susceptibility trends of four Brachyspira species originating from U.S. swine herds and to investigate their associations with the bacterial species, genotypes, and epidemiological origins of the isolates. We evaluated the susceptibility of B. hyodysenteriae, B. hampsonii, Brachyspira pilosicoli, and Brachyspira murdochii to tiamulin, valnemulin, doxycycline, lincomycin, and tylosin by broth microdilution and that to carbadox by agar dilution. In general, Brachyspira species showed high susceptibility to tiamulin, valnemulin, and carbadox, heterogeneous susceptibility to doxycycline, and low susceptibility to lincomycin and tylosin. A trend of decreasing antimicrobial susceptibility by species was observed (B. hampsonii > B. hyodysenteriae > B. murdochii > B. pilosicoli). In general, Brachyspira isolates from the United States were more susceptible to these antimicrobials than were isolates from other countries. Decreased antimicrobial susceptibility was associated with the genotype, stage of production, and production system from which the isolate originated, which highlights the roles of biosecurity and husbandry in disease prevention and control. Finally, this study also highlights the urgent need for Clinical and Laboratory Standards Institute-approved clinical breakpoints for Brachyspira species, to facilitate informed therapeutic and control strategies.