A tale of two antimicrobial resistance reports

I’ll leave the summary of two antimicrobial resistance reports to my friend and hockey colleague (and he’s a professor/veterinarian) Scott Weese of the Worms & Germs Blog (he’s the semi-bald dude behind me in this 15-year-old pic; I’m the goalie; too many pucks to the head):

 Two reports came out this week, both detailing the scourge of antibiotic resistance.

In Canada, the Canadian Council of Academies released “When antibiotics fail: the expert panel on the potential socio-economic impacts of antimicrobial resistance in Canada.

Not to be outdone, the CDC released Antibiotic Resistance Threats in the United States, 2019.

They’re both comprehensive, with a combined >400 pages explaining that this is a big problem.

I’m not going try to summarize the reports. I’ll just pick out a few interesting tidbits.

From the CCA report (Canada):

According to their modelling, first-line antimicrobials (those most commonly used to treat routine infections) helped save at least 17,000 lives in 2018 while generating $6.1 billion in economic activity in Canada. “This contribution is at risk because the number of effective antimicrobials are running out.”

Antimicrobial resistance was estimated to reduce Canada’s GDP by $2 billion in 2018. That’s only going to get worse unless we get our act together. It’s estimated that by 2050, if resistance rates remain unchanged, the impact will be $13 billion per year. If rates continue to increase, that stretches to $21 billion. Remember, that’s just for Canada, a relatively small country from a population standpoint.

Healthcare costs due to resistance (e.g. drugs, increased length of stay in hospital) accounted for $1.4 billion in 2018.  But remember that people who die from resistant infections can actually cost less. If I get a serious resistant infection and die quickly, my healthcare costs are pretty low since I didn’t get prolonged care. All that to say that dollar costs alone don’t capture all the human aspects. Regardless, this cost will likely increase to $20-40 billion per year by 2050.

In terms of human health, resistant infections were estimated to contribute to 14,000 deaths in Canada in 2018, with 5,400 of those directly attributable to the resistant infection (i.e. those deaths would not have occurred if the bug was susceptible to first line drugs). That makes resistance a leading killer, and it’s only going to get worse.

I’ll stop there. The document has a lot of good information and it’s worth reading if you’re interested in the topic.  They also provided a handy 2-page “infographic” summary if you can’t quite stomach the complete 268-page report (also see image below).

From the CDC report (US):

The document’s dedication says a lot. “This report is dedicated to the 48,700 families who lose a loved one each year to antibiotic resistance or Clostridioides difficile, and the countless healthcare providers, public health experts, innovators, and others who are fighting back with everything they have.”

The forward has some great messages too:

To  stop antibiotic resistance, our nation must:

Stop referring to a coming post-antibiotic era—it’s already here. You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution.

Stop playing the blame game. Each person, industry, and country can affect the development of antibiotic resistance. We each have a role to play and should be held accountable to make meaningful progress against this threat.

Stop relying only on new antibiotics that are slow getting to market and that, sadly, these germs will one day render ineffective. We need to adopt aggressive strategies that keep the germs away and infections from occurring in the first place.

Stop believing that antibiotic resistance is a problem “over there” in someone else’s hospital, state, or country—and not in our own backyard. Antibiotic resistance has been found in every U.S. state and in every country across the globe. There is no safe place from antibiotic resistance, but everyone can take action against it. Take action where you can, from handwashing to improving antibiotic use.

Some might say it’s alarmist. However, I don’t think it’s alarmist when someone really should be raising the alarm. We need to talk about it more, not less. We need to get people (including the general public, healthcare workers, farmers, veterinarians, policymakers) on board, to realize it’s a big issue that needs to be addressed now. “Short term pain for long-term gain” certainly applies here. We can keep delaying and the numbers will keep going up, or we can invest in solutions.

The numbers are scary but specific numbers don’t really matter in many ways. “Lots” is all we should have to know to get motivated. However, decision-makers like numbers, so these numbers hopefully will be useful to show the impact and potential benefits of investing in this problem, and motivate them to put money into antimicrobial stewardship. Saving lives should be enough, but that often doesn’t cut it. Antibiotic resistance doesn’t have a good marketing campaign. Everyone knows why people were wearing pink last month and why there are some pretty dodgy moustaches this month. Those are important issues, for sure. However, considering the overall impact, antibiotic stewardship needs to get more people behind it if we’re going to effect change.

You’re such a cute bunny; yes you are; and you can carry dangerous bacteria

Antimicrobial resistance (AMR) in zoonotic (e.g. Salmonella spp.), pathogenic, and opportunistic (e.g. E. coli) bacteria in animals represents a potential reservoir of antimicrobial resistant bacteria and resistance genes to bacteria infecting humans and other animals. This study evaluated the prevalence of E. coli and Salmonella enterica, and the presence of associated AMR in commercial meat, companion, research, and shelter rabbits in Canada. Associations between antimicrobial usage and prevalence of AMR in bacterial isolates were also examined in commercial meat rabbits.

Culture and susceptibility testing was conducted on pooled fecal samples from weanling and adult commercial meat rabbits taken during both summer and winter months (n = 100, 27 farms), and from pooled laboratory (n = 14, 8 laboratory facilities), companion (n = 53), and shelter (n = 15, 4 shelters) rabbit fecal samples.

At the facility level, E. coli was identified in samples from each commercial rabbit farm, laboratory facility, and 3 of 4 shelters, and in 6 of 53 companion rabbit fecal samples. Seventy-nine of 314 (25.2%; CI: 20.7-30.2%) E. coli isolates demonstrated resistance to >1 antimicrobial agent. At least one E. coli isolate resistant to at least one antimicrobial agent was present in samples from 55.6% of commercial farms, and from 25% of each laboratory and shelter facilities, with resistance to tetracycline being most common; no resistance was identified in companion animal samples. Salmonella enterica subsp. was identified exclusively in pooled fecal samples from commercial rabbit farms; Salmonella enterica serovar London from one farm and Salmonella enterica serovar Kentucky from another. The S. Kentucky isolate was resistant to amoxicillin/clavulanic acid, ampicillin, cefoxitin, ceftiofur, ceftriaxone, streptomycin, and tetracycline, whereas the S. London isolate was pansusceptible. Routine use of antimicrobials on commercial meat rabbit farms was not significantly associated with the presence of antimicrobial resistant E. coli or S. enterica on farms; trends towards resistance were present when resistance to specific antimicrobial classes was examined. E. coli was widely prevalent in many Canadian domestic rabbit populations, while S. enterica was rare. The prevalence of AMR in isolated bacteria was variable and most common in isolates from commercial meat rabbits (96% of the AMR isolates were from commercial meat rabbit fecal samples).

Our results highlight that domestic rabbits, and particularly meat rabbits, may be carriers of phenotypically antimicrobial-resistant bacteria and AMR genes, possibly contributing to transmission of these bacteria and their genes to bacteria in humans through food or direct contact, as well as to other co-housed animal species.

Prevalence of antimicrobial resistance in fecal Escherchia coli and Salmonella Enterica in Canadian commercial meat, companion, laboratory, and shelter rabbits (Oryctolagus cuniculus) ad its association with routine antimicrobial use in commercial meat rabbits

Preventative Veterinary Medicine, vol 147, 1 November 2017, Pages 53-57, Jennifer Kylie, Scott A. McEwen, Patrick Boerlin, Richard J. Reid-Smith, J. Scott Weese, Patricia V. Turner, https://doi.org/10.1016/j.prevetmed.2017.09.004


Surf cops: Investigating microbes of surfers and the sea to understand resistance

Peter Andrey Smith of the New York Times writes that on a recent trip, Cliff Kapono hit some of the more popular surf breaks in Ireland, England and Morocco. He’s proudly Native Hawaiian and no stranger to the hunt for the perfect wave. But this time he was chasing something even more unusual: microbial swabs from fellow surfers.

Mr. Kapono, a 29-year-old biochemist earning his doctorate at the University of California, San Diego, heads up the Surfer Biome Project, a unique effort to determine whether routine exposure to the ocean alters the microbial communities of the body, and whether those alterations might have consequences for surfers — and for the rest of us.

Mr. Kapono has collected more than 500 samples by rubbing cotton-tipped swabs over the heads, mouths, navels and other parts of surfers’ bodies, as well as their boards. Volunteers also donate a fecal sample.

He uses mass spectrometry to create high-resolution maps of the chemical metabolites found in each sample. “We have the ability to see the molecular world, whether it’s bacteria or a fungus or the chemical molecules,” he said.

Then, working in collaboration with U.C.S.D.’s Center for Microbiome Innovation — a quick jaunt across the quad from his lab — Mr. Kapono and his colleagues sequence and map the microbes found on this unusually amphibious demographic.

He and his colleagues are looking for signs of antibiotic-resistant organisms. Part of their aim is to determine whether, and to what extent, the ocean spreads the genes for resistance.

Many antibiotics used today derive from chemicals produced by microbes to defend themselves or to attack other microorganisms. No surprise, then, that strains of competing bacteria have also evolved the genetic means to shrug off these chemicals.

While drug resistance comes about because of antibiotic overuse, the genes responsible for creating resistance are widely disseminated in nature and have been evolving in microbes for eons. Startlingly, that means genes giving rise to drug resistance can be found in places untouched by modern antibiotics.

Several years ago, researchers identified antibiotic-resistant genes in a sample of ancient permafrost from Nunavut, in the Canadian Arctic. William Hanage, an epidemiologist at the Harvard School of Public Health, was among those showing that these genes conferred a resistance to amikacin, a semi-synthetic drug that did not exist before the 1970s.

“There was a gene that encoded resistance to it in something that was alive 6,000 years ago,” he said in an interview.

Another group led by Hazel Barton, a microbiologist at the University of Akron, discovered microorganisms harboring antibiotic-resistance genes in the Lechuguilla Cave in New Mexico. These bacteria, called Paenibacillus sp. LC231, have been isolated from Earth’s surface for four million years, yet testing showed they were capable of fending off 26 of 40 modern antibiotics.

It’s all cool research, but all I could think of was Celebrity, a skit by The Kids in the Hall.

Hang 10, you’re booked.

UK regulator types on antimicrobial resistance in food

In 1969, the Swann report recommended strict oversight and restrictions on the use of antibiotics used in human medicine as growth promoters in agriculture. That was in the UK, and 37 years later, the UK Food Standards Agency has published a systematic review of the available evidence on antimicrobial resistance (AMR) in food. The review looked at research on the presence of AMR in bacteria in a number of different foods sold at retail.

fda-antibiotics-agricultureThe research has confirmed the need for extra surveillance of AMR in food at retail level, to support the wider programme of work currently underway across government to help reduce levels of AMR.

The study was produced by the Royal Veterinary College, on behalf of the Food Standards Agency, and looked at the areas where consumers are more likely to be exposed to AMR in bacteria from the food chain. Researchers examined published evidence between 1999 and 2016 for pork and poultry meat, dairy products, seafood and fresh produce sold in shops.

FSA action includes:

Working to encourage the adoption of clear transparent reporting standards that help consumers have access to and understand information about the responsible use of antibiotics in the food chain. 

Continued focus on improving the scientific evidence base relating to antimicrobial resistance in the food chain through supporting relevant research and improving surveillance. 

Setting up an independent group to advise us on responsible use of antibiotics in agriculture to support the above work.


Antimicrobial resistance (AMR) is a major public health issue worldwide. It is a complex issue driven by a variety of interconnected factors enabling microorganisms to withstand antimicrobial treatments to which they were once susceptible. The overuse and/or misuse of antibiotics has been linked to increasing the emergence and spread of microorganisms which are resistant to them, rendering treatment ineffective and posing a risk to public health.

People can become exposed to AMR bacteria through a number of routes such as human-to-human spread, animals, through the environment and food chain. There is currently uncertainty around the contribution food makes to the problem of AMR and the types of AMR bacteria found in foods on retail sale in the UK. There is a need to consider the literature in this area to gain a better understanding of the potential risk to consumers through contaminated foods and also to identify the key evidence gaps.

Research Approach

The aim of this study was to assess the prevalence of antimicrobial resistant bacteria in retail pork, poultry meat, dairy products, seafood and fresh produce that could pose a risk to UK consumers. For this purpose a systematic review was undertaken following the PRISMA guidelines (Liberati et al., 2009) through which current existing evidence present in scientific databases and grey literature is collected and assessed. A protocol, which describes the methodology used, has been made accessible through the International Prospective Register of Systematic Reviews (PROSPERO). The protocol is available at http://www.york.ac.uk/crd/. Please search PROSPERO using registration number CRD42016033082.

ab-res-prudent-may-14Research questions were developed taking into consideration current evidence for relevant resistant foodborne pathogens and commensal bacteria observed in animals, food and humans in European countries published by the European Food Safety Authority (EFSA) (EFSA, 2015), feedback provided by experts and findings from scoping searches of the literature (i.e. PubMed).

Key recommendations: 

There is a need to standardise the selection of antimicrobials for antimicrobial susceptibility testing panels, harmonising criteria for assessment of resistance per bacteria/drug combination for surveillance purposes, using a standardised definition for multidrug resistance (MDR) and the adoption of random sampling and adequate study design for epidemiological studies.

Identification of a core set of relevant antimicrobials when developing and implementing prospective testing for surveillance systems for determination of AMR in the food chain.

Surveillance priorities could be set using a risk-based approach, taking into account the importance of antimicrobials used for treatment in both humans and animals, and continued surveillance of the incidence and emerging resistance (including MDR) in commensal bacteria (Enterococcus spp. and E. coli) should be encouraged.

Data on AMR bacteria from British and imported pork meat in the UK are limited and dated. Further research and surveillance efforts are needed to ascertain AMR levels in both foodborne and commensal bacteria in pork meat in the UK.

There is evidence of increasing levels of resistance to antimicrobials in foodborne bacteria (i.e., Campylobacter spp.) from poultry meat in the UK. Research and surveillance efforts should be continued to monitor AMR trends in both foodborne and commensal bacteria in British and imported chicken and poultry meats in the UK.

There is a lack of information on AMR bacteria in foods of animal origin other than meat at retail level. In recent years, there have been growing numbers of outbreaks associated with milk and dairy products (cheese, butter, yogurt), seafood (fish and shellfish) and fresh produce (fruit, vegetables and salads) at national and international levels but there is scarce, scattered evidence of resistance and MDR occurrence in foodborne and commensal bacteria in these food products and its implications for public health. These gaps should be addressed also using a risk-based approach following evidence of resistance in food items as well as the extent of expected consumer exposure using consumption and import volumes.

Data on antimicrobial usage in food-producing animals in the UK are important to explain the occurrence and dynamics of AMR, resistance genes and MDR phenotypes in a defined geographical area. More complete information should therefore be collected on the type of production system from which food samples originate to assess the impact of animal husbandry practices as risk factors for resistance.

There is a need for more studies to quantify the contribution of both domestic and imported foods to AMR occurrence. Information on country of origin for imported products should be collected.

Priorities should be set according to the importance of a food item in terms of exposure of consumers. Consumption data will be essential for assessing the risk of exposure of British consumers.

Finally, further research and surveillance are needed to establish and quantify the risk of transmission of AMR against critically important antimicrobials in organisms from foods of animal and non-animal origin) to humans.

A systematic review of AMR bacteria in pork, poultry, dairy products, seafood and fresh produce at UK retail level

August 2015-October 2016

Food Standards Agency


Yes, your cat is trying to kill you: Antibiotic-resistant Salmonella found in Australian cat

Microbiology is not a Marvel comic strip: Not every bacteria is a superbug.

data-spotResistance is not futile.

But it is normal.

A drug-resistant salmonella strain that could infect humans and livestock has been found in Australia for the first time.

The salmonella superbug was discovered in an infected cat after it was taken from a shelter to a Sydney vet last year with a suspected gut infection, ABC News reported.

The ‘highly transferrable’ bacteria is resistant to carbapenems- a life-saving drug used in Australian hospitals.

This rare drug resistance could pose a serious threat to public health, experts believe.

‘This is the first time that a salmonella strain with resistance to most drugs has been reported in any Australian domestic animal and it is a significant concern to public health, Dr Sam Abraham told the publication.

Mr Abraham led a study into the risks of the dangerous salmonella strain with a team of veterinary and medical researchers.

He describes the bacteria as a ‘superbug’ because it has picked up a piece of DNA that gives it ‘super powers or resistance to about nine classes of drugs that we usually use to treat humans and animals’.

The study led by Abraham has been accepted for publication in Scientific Reports.

So what? It’s not like other mortals can see it. Publication before press release. Otherwise, Cake has it covered (NSFV).

Same with the U.S. election.

Fire your PR firm: Sanderson Farms takes on misleading food labels

In a new ad campaign recently released by Sanderson Farms, Inc., the company seeks to educate the public on common misconceptions surrounding the use of antibiotics in poultry production, while exposing marketing gimmicks designed to mislead consumers and sell products at a higher price.

Schooner-TunaSorry, you lost me at educate consumers. My mom the kindergarten teacher for 40 years could tell you how to educate folks.

So maybe switch to providing information.

Lead with a positive, not a negative, and especially not bashing the media.

You don’t say why antibiotics are useful.

And you make no emotional connection with the buying public.

Yes, trash others for using shit messages, but get emotional about it.

I like the clip, below, from my unintentional biography, Mr. Mom.

“At Sanderson Farms, we have a responsibility to empower consumers to make informed decisions by debunking the myths perpetuated through the media and the unfortunate use of misleading labels,” said Joe F. Sanderson, Jr., CEO and chairman of the board for Sanderson Farms. “Some in the industry, by way of their labels and advertising efforts, have misled consumers to believe that only their chicken is raised cage free and is free of antibiotics and added hormones. The fact is that FDA regulations require all chicken made available for purchase be free of antibiotic residues and the use of added hormones has been illegal since the 1950’s.”

“As long as scientific research indicates that antibiotics are safe and healthy, we’ll continue to make the right decision when it comes to how we raise our chickens for our customers. Sanderson Farms’ number one priority continues to be providing our consumers with safe, wholesome, high-quality chicken,” Sanderson concluded.

Sanderson Farms’ position on the responsible use of antibiotics is supported by experts across the industry who agree with their position on the responsible use of antibiotics in food-producing animals. This includes a full range of specially-trained veterinary scientists and nutritionists that continuously research and study the best practices for maintaining the best health and well-being of flocks raised for food.

For more information on the facts surrounding the responsible use of antibiotics, please visit www.SandersonFarms.com


Doering speaks: Prudent use of antibiotics in animal production

Ron Doering, the first president of the Canadian Food Inspection Agency, writes for Food in Canada that while the medical community recognizes that the emergence and spread of antimicrobial resistance (AMR) in humans is a potential disaster for humanity, and that it is the overuse of antimicrobials in human medicine that is the largest contributor, there is still a broad consensus that the use of antibiotics in animals may contribute to the problem, though ron.doeringthe degree is still unclear.

The scale of the AMR crisis was dramatically demonstrated recently with the release on May 19, 2016 of a landmark re- port to the U.K. government that reckons that drug-proof bugs already kill 700,000 people a year and warns that that number is likely to rise to at least 10 million by 2050. I wrote a series of articles for this magazine in 2013 and in the spring of 2014 discussing various reports that attempted to assess the extent to which antibiotics in animals contributed to the crisis and I identified a number of regulatory changes to mitigate the problem that were necessary and long overdue.

 At spring the Canadian Animal Health Institute (CAHI), the trade association representing Canadian veterinary drug manufacturers, and Health Canada (HC) announced their intention to work together to develop a policy on prudent use of antibiotics. They promised (1) the removal of growth promotion and/or production claims of medically important antimicrobial (MIA) drugs and (2) to develop options to strengthen veterinary oversight of antimicrobial use in food animals. At the same time producer organizations were developing strategies to promote more prudent on-farm use, and veterinary groups undertook to develop new policies and procedures.

So, after all the promises, undertakings and commitments, how are we doing? I’m delighted to report: pretty well.

In March 2015 the Harper government announced the Federal Action Plan on Antimicrobial Resistance and Use, committing to move expeditiously on several regulatory reforms. I’m told that notices in Canada Gazette I are imminent and that these will bring in regulatory amendments that will remove growth promotion claims for all MIAs. Moreover, all MIAs used in feed and water would come under prescription drug status, bringing them under the oversight of veterinarians. CAHI estimates that this would bring 140 drugs under veterinary oversight.

I’m pleased to report as well that the federal government is finally taking steps to address the longstanding problem of animal owners taking advantage of HC’s own use importation provisions (OUI) to import for personal use active pharmaceutical ingredients (API) that are not approved for sale in Canada.

There are several problems with this regulatory gap, including the inability to know which antimicrobials are used in Canada, in what quantities and for what purposes. The new regulations will forbid animal owners to import MIA in finished form from other countries.

Major producer groups continue to take concrete steps to address the AMR issue.  The Canadian Pork Council continues to operate its model quality assurance scheme (CQA), which applies to all its members and represents over 90 per cent of hogs slaughtered in Canada.  The Chicken Farmers of Canada has embarked on a comprehensive process to develop and apply strict new rules to ensure prudent use.

ab.res.prudent.may.14The Canadian Council of Veterinary Registrars and the Canadian Veterinary Medical Association have been slow in responding to the challenge of AMR, but they have now developed a comprehensive plan and a detailed set of recommendations that will be the main topic for their annual meeting this summer. Veterinary medicine is a provincially regulated profession so getting all jurisdictions to co-operate to create a truly national system is not easy, but they seem to have made good progress in the last two years.

The food industry is always happy to respond to market demands for new food attributes, especially when it can charge a premium for them, and even when most of these claimed attributes (like, say, organic) will have no positive effect on safety, taste, quality or sustainability. Proof of prudent use of antibiotics is not one of these. While there is more work to be done, Canadian regulators, producers, processors and retailers have made remarkable strides to respond to the legitimate concern posed by AMR.

Bacteria have always been promiscuous: Different resistant E coli strains can cross-protect

Two strains of bacteria resistant to different antibiotics can protect each other in an environment where both drugs are present, according to the first experimental study of microbial cross-protection published last week in Proceedings of the National Academy of Sciences (PNAS).

bob-carol-ted-aliceResearchers from the Massachusetts Institute of Technology (MIT) Department of Physics explored the potential of mutualism—an interaction that benefits two different species—on two strains of Escherichia coli, one of which was resistant to ampicillin and the other resistant to chloramphenicol.

Though the type of mutualism known as cross-protection, in which species depend on each other for survival in a challenging environment, has been observed in larger animals, it has not previously been observed experimentally in bacterial populations, the authors noted.

Cross-protection in drug-resistant E coli depended on a host of factors, including characteristics of each resistant strain, presence and amount of antibiotics, dilution and oscillation of bacterial population abundance, and invasion by other bacteria.

The role of enzyme deactivation

Strains of E coli express antibiotic resistance by producing defensive enzymes that destroy the drug. Resistant strains can often protect drug-susceptible pathogens through enzyme deactivation if they are able to quickly remove the antimicrobials from the environment, the authors said.

During a 10-day experiment, researchers exposed an ampicillin-resistant and a chloramphenicol-resistant E coli strain to mixed concentrations of the antibiotics that should have killed each strain alone. Ampicillin-resistant E coli cannot survive alone in a chloramphenicol concentration above 2.2 micrograms per milliliter (mcg/mL), and a chloramphenicol-resistant strain will be destroyed when exposed to 2 mcg/mL of ampicillin.

Even when bacterial populations were diluted each day by transferring 1% of the colonies to a new test tube containing antibiotics, the strains were able to protect each other against drug concentrations fourfold higher than amounts lethal to one strain alone.

“A coculture of the two strains can survive above the concentrations at which the individual strains survive alone, indicating that the two populations form an obligatory mutualism,” the authors wrote.

e_coli-eraxion-istockA key contributor to cross-protection between two resistant bacterial strains was each population’s ability to oscillate in size when diluted daily in a solution containing ampicillin and chloramphenicol. Oscillation cycles lasted for 3 days and involved massive changes in the percentage of each strain while the total size of the bacterial population remained stable.

During a 3-day oscillation cycle, the ampicillin-resistant strain grew in abundance as it deactivated the antibiotic. This activity allowed the chloramphenicol-resistant strain to grow, removing chloramphenicol from the environment, until the ampicillin-resistant strain could increase again, thus continuing a cycle in which the strains protected and overtook each other in abundance. Populations varied by up to 1,000% over the 3-day range, the authors said.

Oscillations in abundance occurred because of the daily dilution in an antibiotic-rich environment and were not related to different natural growth rates in each strain, the author said. The cross-protective effect achieved by the oscillations appeared stable, with shifts in each strain’s growth and relative proportion likely being sustainable over time.

“Because these oscillations occurred with a period (3 days) longer than the period of the daily dilution (1 day), they were not a trivial consequence of the daily growth-dilution cycle,” the authors said.

Oscillation cycles had to be precisely balanced to prevent the cross-protective interaction’s total collapse. At chloramphenicol concentrations of 7.6 mcg/mL, both bacterial populations were able to achieve stable oscillations and coexist. When exposed to chloramphenicol levels of 17.1 mcg/mL, however, the oscillations became erratic, the sustainable 3-day cycle was lost, and the interaction collapsed, the probability of which increased at chloramphenicol concentrations of 38.4 mcg/mL.

Frequently diluting small concentrations of bacteria in media containing 10 mcg/mL of ampicillin and 5.1 mcg/mL of chloramphenicol allowed the bacterial populations to form a stable cross-protective relationship.

“In a continuous culture experiment in which the antibiotics are continuously added (and cells continuously removed), there will be no oscillations in the population abundances, and instead the ratio between the two strains should approach a stable equilibrium,” the authors wrote.

The introduction of an individual E coli strain resistant to both antibiotics also caused the cross-protective behavior to collapse, the authors said.

When researchers added a small number of double-resistant E coli cells to the dilutions at the beginning of the seventh growth cycle, the double-resistant strain displaced the ampicillin-resistant E coli and co-existed with the chlorampenicol-resistant strain in a solution containing concentrations of ampicillin at 10 mcg/mL and chloramphenicol at 7.5 mcg/mL.

“A double-resistant strain can invade the mutualism and cause the oscillations to vanish, illustrating that the existence of oscillations depends on how resistance is allocated in the microbial population,” the authors said.

In the absence of a multi–drug-resistant microbial invasion, horizontal gene transfer in the cross-protective co-culture could create a double-resistant mutant strain, the authors said. In addition, “the cooperative nature of antibiotic deactivation could allow a sensitive strain to use the two mutualists for protection.”

Implications for infection and resistance

Because cross-protection often arises as a strategy to help survive a harsh environment, greater understanding is needed about both the environment and the microbial population dynamics, including the role of oscillations in strain abundance, under which mutualistic behavior allows bacterial resilience in the presence of antibiotics. The authors note that little knowledge is available about the role and cause of oscillations in stabilizing population abundance even as they occur in more easily observable organisms, such as the Canada lynx and snowshoe hare.

Many cross-protective relationships are the result of two organisms co-evolving in the same environment, though this is not the case with E coli strains. Mutualistic behavior in this case is thought to arise as a result of exposure to antibiotics, the authors said.

“Whether an interaction is cooperative or competitive can depend on the environment,” the authors wrote, adding that exposing cross-protective strains to antibiotics can fuel the development of multi-drug resistance by buying time for further evolutionary adaptation.

Co-occurrence, co-localization, co-selection: Antimicrobial resistance in agriculture

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear.



Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions.

We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa.

Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.

Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. As governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.

Clusters of antibiotic resistance genes enrich together stay together in swine agriculture

Timothy A. Johnsona,b,f, Robert D. Stedtfelda,c, Qiong Wanga, James R. Colea, Syed A. Hashshama,c, Torey Looftf, Yong-Guan Zhud,e, James M. Tiedjea,b


mBio, Volume 7, Number 2, doi: 10.1128/mBio.02214-15


A review on antimicrobial resistance in agriculture is also available.

In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans.

Sophie Thannera, David Drissnerb,  Fiona Walshc


mBio, Volume 7, Number 2, doi: 10.1128/mBio.02227-1


Pork producers: Be ready for public and regulatory scrutiny

On Thursday morning (March 3, 2016) CBS news aired a story on fast food restaurants’ move to provide meats from production systems that implement antibiotic-free practices. Before the echo of the sound bites had faded, the communications team of the National Pork Board went to work to help correct some of the inaccuracies in the CBS presentation.

pigs.pork.producersKevin Waetke, NPB vice president of Strategic Communications, submitted a response on behalf of the NPB, stating “The National Pork Board supports a consumer’s desire for greater food transparency, but it is critical that information shared with them is accurate and not sensational in its approach. The 60,000 pig farmers we represent have been preparing the past 18 months for the very real and substantive changes that are occurring on pig farms across the country in regard to responsible antibiotic use. … Preserving the effectiveness of medically important antibiotics is critical in our commitment to ensure a safe food supply and to build consumer trust. Consumers must understand three key concepts:

Safe Food Comes from Healthy Animals — Decisions to use antibiotics are unique to each farm, regardless of farm size, and require the oversight of both farmers and veterinarians working together. Antibiotics are used when needed to address disease challenges, to keep animals healthy and to produce safe food. It is not possible to raise all pigs without antibiotics. Some pigs will get sick and need treatment. To not treat them would be inhumane, resulting in reduced animal welfare and increased concerns about food safety.

Antibiotics and Antibiotic-Resistant Bacteria in Meat — The USDA Food Safety and Inspection Service tests meat for antibiotic residues to ensure consumers with a safe product in the meat case and in restaurants. Additionally, antibiotic-resistant bacteria is tracked by the federal government. Through a collaborative effort among the CDC, FDA and USDA, the National Antimicrobial Resistance Monitoring System tracks specific resistant bacteria in humans, animals and retail meat. To date, there are not any patterns from the NARMS research that show resistant bacteria are routinely transferred from animals to humans.

Cost of Antibiotic-Free Meat — It is inaccurate for the Consumers Union to state that the ‘price of meals probably will not go up much, if at all,’ as they do not have a current grasp on the state of the industry. Although some suppliers have begun to test the market demand for pork from pigs raised without antibiotics, others have chosen to not pursue this option. Based on current market dynamics, consumers do have to pay more for pork from pigs raised without antibiotics.”

As the CBS story proves, the education mission of the NPB goes beyond that of only pork producers. The NPB and the producers themselves need to take the lead on engaging, educating and informing their neighbors, as well as their urban friends on the responsible pork production practices.

Responsible production practices involve the responsible use of antibiotics, and the issue was heavily included in formal and informal discussions during Pork Forum. These discussions need to continue long after Forum, as well as long after the new rules take effect with the flip of the calendar. These discussions are also being taken to those fast-food companies who have pledged to provide meat produced in antibiotic-free production systems. That pledge in itself may go against the very nature of responsible production practices.

Though no industry likes to be told how to do their business, especially by misinformed or under-informed organizations or consumers, it is the reality of the world. However, it never does hurt for the industry or individual producers to reevaluate or reassess what has become business-as-usual.

A solid producer-veterinarian relationship should have already been developed, but the Jan. 1 regulations will require a Veterinary-Client-Patient Relationship. Producers need to use this veterinary relationship to their benefit. If you haven’t already, have discussions with your herd veterinarian of how your operation fits into these new rules.