0 comments on “Zinc, Pigs and the Meaning of Antimicrobial Stewardship”

Zinc, Pigs and the Meaning of Antimicrobial Stewardship

Bacteria are smarter than we give them credit for.
Or maybe we’re not a bright as we think we are.

Antimicrobial stewardship is sometimes (wrongly) assumed to simply be the practice of ‘using fewer antimicrobials’. It’s more complex than that, because the issue is complex. At face value, using overall reduction in antimicrobial use is a logical target, and it’s true that it is a big aspect of stewardship.

However, what is an ‘antibiotic’?

“Raised without antibiotics” and “Antibiotic-free” are good marketing terms, but what do they mean in terms of antimicrobial resistance? That’s less clear.

In pig production, control of post weaning E. coli diarrhea is a big problem. Prophylactic antibiotics are effective for this, but that’s not ideal. The main thing that’s done to replace antibiotics is to add a lot of zinc to the piglets’ diets at that age.

  • The reason….zinc kills bacteria.
  • The problem…bacteria don’t care whether we call it an antibiotic, just that it’s trying to kill them. So, they try to resist it.
  • The bigger problem….the way the resist it can be linked to the way they resist conventional antibiotics.

We (and others) have previously shown that addition of high levels of zinc to the diet of piglets selects as well for MRSA (methicillin-resistant Staphylococcus aureus) as tetracycline, the commonly used antibiotic for prevention of post-weaning diarrhea. If zinc selects for MRSA but not other resistant bugs, while tetracycline selects for a broader range of resistance, zinc use still might be of concern, but it would be a better option than tetracycline. However, that’s not the case and a recent paper in PLOS ONE (Ciesinski et al 2018) provides more information on the impact on other important resistant bacteria.

In that study, they took a typical approach of feeding groups of pigs either low levels (dietary requirements) or high levels (antibacterial levels) of zinc, and they investigated what happens with E. coli. They found significantly higher levels of multi drug resistant E. coli in association with feeding high levels of zinc: 5.8-14% in the control group compared to 29-30% in the high level zinc group. This appeared to be because the resistant strains persisted better than susceptible strains, as numbers of E. coli didn’t increase, but the proportion of resistant strains did.

Does this mean we shouldn’t be feeding high levels of zinc to piglet?

  • I don’t know. Prevention of disease is important for various reasons, including piglet welfare, reduced need to use therapeutic antibiotics (which are often more important drug classes than those used for prevention) and the need for economic production of safe food.
  • Whether antibiotics or zinc are better (or less worse) for resistance in piglets and the corresponding human risk is still unclear.
  • Another unanswered question is the impact of high levels of zinc in manure, since that ultimately makes its way into the ecosystem (just like some antibiotic residues).

However, it provides more evidence that ‘common sense isn’t evidence’ when it comes to antimicrobial resistance. We can’t assume things will have positive or negative aspects because ‘it makes sense’. We need proper research to figure out the best ways to optimize and improve antimicrobial use, minimizing resistance while maximizing the care of people and animals.
That’s antimicrobial stewardship.

JSW

0 comments on “Show Me The Data (But Also Do Something With It)”

Show Me The Data (But Also Do Something With It)

Surveillance is an important aspect of antimicrobial stewardship. Knowing where we stand, whether it’s the amount of drug used, the types of drugs that are used, the prevalence resistance or various other types of data, is important. That’s why there’s a lot of effort put into surveillance.So good

However, data need to be used to have a real impact. That can involve setting targets, identifying areas where interventions are needed, developing and testing interventions and similar things that aim to reduce or optimize antimicrobial use, not just tell us what’s happening.

Sometimes the action component gets lost, since analyzing data can be a lot easier (and less expensive, and less time consuming) than effecting change.

So, linking those areas is important, as is figuring out how to get better data (and…not-so-subtle CANresist plug here….something we need to do more of.)

  • A commentary in the Veterinary Record (Coyne et al, Dec 2017) entitled Antimicrobial use in dairy cattle; what gets measured gets improved highlights some important issues.. A research paper in the same edition of that journal (Hyde et al) reports on changes in antimicrobial use on UK dairy farms.

A few highlights:

They looked at a few different ways to assess antimicrobial use, including mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses (DDDvet) and defined course doses (DCDvet).

  • It’s a challenge to accurately capture use on farms (and other places) because of the ways antimicrobials are dispensed and used, but with a standard approach, changes over time can be assessed with a good degree of confidence. It also highlighted some of the problems we have with surveillance, including how to report data. Reporting kg of drug used is pretty crude. Defined daily doses and other metrics used in humans are hard to accurately apply in animals, with markedly different weights and limited animal-specific use data. In dairy cattle, intramammary antibiotics are commonly used, something that defies accurate capture using some reporting approaches.

There was a lot of variation, with use of farms ranging from 0.36 to 97.79 mg/PCU and 0.05 to 20.29 DDDvet.

  • That gives a snapshot of the farms that were studied, and it shows that there is at least a subset of farms that are ripe for an intervention. That’s step 1. Figuring out why their antibiotic use is so high is step 2, helping them drop it is step 3, and more surveillance to see if the rates actually drop is step 4. All are important and it’s critical to keep going after step 1.

25% of farms accounted for over 50% of antibiotic use.

  • Targeting those farms can obviously have a big impact overall.

The commentary states “This work emphasises the need for accurate baseline antimicrobial use data which is representative of the national dairy herd . Identifying such high antimicrobial use behaviours will allow the industry to better target antimicrobial use interventions to reduce use at a farm, veterinary practice and national level. Due to the wide spectrum of antimicrobial use recorded by Hyde and others, there is a need to approach antimicrobial reduction interventions at an individual farm level. For example, benchmarking can improve farmer awareness of their current antimicrobial use practices and may play a role in reducing high antimicrobial use behaviours and promoting prudent use.”

We can replace “national dairy herd” with every other species (including people), and add humans healthcare facilities and the community and this statement would still be accurate.

JSW

1 comment on “Antimicrobial Use in Food Animals: USA”

Antimicrobial Use in Food Animals: USA

Recently, we had a series of posts about the CAHSS report, including both human and animal antimicrobial use trends. Now, how about some US animal data to add to the mix?

The USDA has released their 2016 report on antimicrobial sales and use in food animals. It’s a big report that I assume most of you won’t want to read in full, so here are some highlights.

Antibiotic sales and distribution dropped by 10% from 2015-2016.

  • Pretty impressive.

Cattle and pigs battled for the biggest users, with moos edging out oinks.

Medically-important antibiotics encompasses pretty much anything used in humans, so it’s a broad group. Use of this group decreased in 14% from 2015 to 2016. Overall, 60% of antibiotics used in food animals were medically important. The majority of this (70%) was tetracyclines.

  • That’s not surprising, given how they are used in food animal species. It’s also a ton of drugs (figuratively….literally, it was many tonnes, with 5,866,588 kg used in 2016).
  • That a lot, but down 15%.
  • The good news is that tetracycline are in the lowest group of the medically important antibiotics.
  • Still, that’s a lot of antibiotics and probably a big area where further reductions could occur without negative impacts.

Cephalosporins and fluoroquinolones, two critically important drug classes, each accounted for <1% of use. Most of the cephalosporin use was in cattle.

  • Good news (although we can still be better).

As expected, chickens led the way in relative use of not medically important drugs.

  • There are a few reasons for that, including the diseases of greatest relevance and active efforts to curtail use of certain drugs.

In-feed use was most common, followed by in water use. Individual animal treatment accounted for a much lower percentage.

It’s hard to say whether this is all good news, bad new, or just news. Reductions are good. However, looking at kgs of drugs only tells a very small part of the story. Much more refined information is needed, along with efforts to reduce antibiotic use while avoiding impacts on animal health, welfare and productivity. It’s not an easy area to address, as it’s a complex problem that will require complex solutions.

0 comments on “Global Antibiotic Use in Animals”

Global Antibiotic Use in Animals

We tweeted a question yesterday (#CANADAresist) asking people to guess which countries use the most antimicrobials in animals and which ones are expected to increase the most by 2030. Antibiotic use in animals is moving (and in some countries, very hard to hit) target, but a 2015 study (Van Boeckel et al, Global Trends in Antimicrobial Use in Food Animals) has some answers.

The dubious winners: China, USA, Brazil, India and Germany.

  • Those make sense, as large countries with large food animal production systems.

Predicting the future of antibiotic use is hard, and hopefully the 2030 estimates will be high because of antimicrobial stewardship programs, but the authors predicted that the list in 2030 will be: China, USA, Brazil, India, Mexico

  • Again, those make sense. Lots of people. Lots of farms. Growing populations and economies.

Another interesting number is the predicted relative increase. I suspect most of us wouldn’t have guessed these.

  • Here, Indonesia takes the lead, followed by Myanmar, Nigeria, Peru and the Philippines.

Screen Shot 2017-11-22 at 8.10.50 AM

Data like these are just more examples of why antimicrobial stewardship programs need to develop and need to take on an international tone. Trying to attack a complex problem in isolation (either looking only at one country or looking only at animals or humans) can’t be the answer. Complex problems need complex solutions.

1 comment on “CPE in Animals”

CPE in Animals

Continuing our World Antibiotic Awareness Week blitz, let’s head back to the 2017 Canadian Antimicrobial Resistance Surveillance System report

Carbapenase-producing Enterobacteriaceae (CPE) are Gram negative bacteria (e..g E. coli, Klebsiella, Enterobacter) that are resistant to carbapenems, an important class of antibiotics. They’re a big concern because carbapenems are used for people with serious infections, and treatment options may be limited (since these strains are often resistant to many other drug classes too). Carbapenems aren’t used in food animals and are rarely used in companion animals, but resistance can be found in bacteria from animals. It’s probably driven by use of other antibiotic classes that are used in food animals that CPE are also resistant to. A big issue is that these bacteria are common inhabitants of the gut. Therefore, resistant strains can live happily in the intestinal tract for potentially long period of time, being passed in feces. (I probably don’t need to point out that cows poop a lot).

In Canada, screening of farm, slaughterhouse and retail samples was started in 2013, with a new technique added in 2016 to provide more sensitive detection.

  • The good news….no CPE were identified amongst over 13,000 screened surveillance isolates.
  • The somewhat concerning news….9/3,000 farm/retail/slaughterhouse samples were positive. That’s obviously a low rate but it’s not zero. All were seafood products. Three are stated as being imported, while my assumption is the other 6 were too (although I could be wrong…it’s not clear in the report). This highlights the fact that we don’t live in a bubble and bacteria could case less about immigration rules.

The fact that no CPE were identified in livestock or their associated products was great.

For now, at least.

It will probably happen but continued surveillance to identify and hopefully mitigate risks like this is important. We’re also continuing to look for CPE in companion animals. I’ve dealt with a few cases, but all were from the US. CPE in pets may end up similar to the situation with MRSA, whereby infections in pets are most often associated with transmission from infected owners, but food animals, food and the environment all remain potential ways that CPE could be spread from livestock.

At this point, CPE is rare in people in the community, but if it successfully spills out into the community from hospitals, we’ll likely see further spillover into domestic animals. Yet another reason why a multisector approach to antimicrobial stewardship is needed (yes, that’s a plug for CANresist, but it’s true).

JSW

0 comments on “Antibiotic Resistance Surveillance Report: 2017”

Antibiotic Resistance Surveillance Report: 2017

The 2017 Canadian Antimicrobial Resistance Surveillance System report was just released, and as always it contains a lot of interesting data. Some are interesting, some are concerning, some are encouraging.

I’m not going to try to distill a 90 page report into a quick blog post, so I’ll cover some highlights separately. Let’s start with the Antimicrobial Use in Animals section. Here are some highlights (and some comments).

In 2016, ~1 million kgs of medically important antimicrobials were distributed for sale in Canada.

  • This misses some antibiotics that get used via loopholes, but those are being closed and this number is probably a pretty good overall estimate.
  • The great news…that’s 14% lower than 2007 and 17% lower than 2015

600,000 kg of ionophores and chemical coccidiostats were also distributed.

  • These are often combined with other antimicrobials (sometimes to make things look scarier) but they are irrelevant from antibiotic-resistance and public health standpoints. So, it’s good to see them separate (and to essentially ignore them).

99% were intended for food animals, on a per kg basis.

  • This is always hard to interpret and sometimes leads people to think that companion animals are irrelevant. We have to be a bit wary focusing just on per kilogram data (1 kg of antibiotic treats a lot more Chihuahuas than cattle). The main antibiotic classes used in companion animals were cephalosporins, beta-lactams and trimethoprim-sulfa, all drug classes of high importance.
  • What this shows to me is that we can have a huge impact on overall use focusing on food animals. However, the drugs that are used in pets are often the same as those used for serious infections in people, and we share bugs readily with our pets. So this numbers shouldn’t be taken as an indication to ignore them.

Fluoroquinolones decreased by 56% from 2015 to 2016.

  • Wow. That’s great, since this is one of the biggest classes we’re worried about. They’re important drugs (for both humans and some animal species) but are prone to overuse.

Most of the distributed antibiotics were those intended for use in feed, accounting for 76% overall. On the opposite end of the spectrum, intramammary drugs (used for mastitis in cattle) accounted for <1%.

When everything is put together on a per kg basis, 78% of antimicrobials distributed or sold in 2016 were for food animals, 20% were for humans, 1% for crops and 1% for companion animals.

  • Again, be somewhat wary of crude kg numbers (since the relevance of a kg of tetracycline is probably much, much less than a kg of a fluoroquinolone) and there are approximately 19 times more animals in Canada (excluding farmed fish) than humans, but they give some idea of how we use antimicrobials in this country and they give us numbers for comparison over time. The 2nd figure below is an interesting on to think about.

Some people will take these numbers and use them to spin certain agenda. However, we’re better off using them as the basis for more surveillance, more interventions and more research to reduce and improve use of antibiotics in Canada, whatever species they go into.

1 copy

2 copy

0 comments on “WHO Guidelines on Use of Medically Important Antimicrobials in Food-Producing Animals”

WHO Guidelines on Use of Medically Important Antimicrobials in Food-Producing Animals

The World Health Organization released new guidelines on the use of ‘medically important antimicrobials’ in food animals. Here’s a list of their recommendations, along with the strength of recommendation and quality of evidence.

  1. We recommend an overall reduction in use of all classes of medically important antimicrobials in food-producing animals (Strong recommendation, low quality evidence)
  2. We recommend complete restriction of use of all classes of medically important antimicrobials in food-producing animals for growth promotion (Strong recommendation, low quality evidence)
  3. We recommend complete restriction of use of all classes of medically important antimicrobials in food-producing animals for prevention of infectious diseases that have not yet been clinically diagnosed (Strong recommendation, low quality evidence)
  4. We suggest that antimicrobials classified as critically important for human medicine should not be used for control of the dissemination of a clinically diagnosed infectious disease identified within a group of food-producing animals (Conditional recommendation, very low quality evidence)
  5. We suggest that antimicrobials classified as highest priority critically important for human medicine should not be used for treatment of food-producing animals with a clinically diagnosed infectious disease (Conditional recommendation, very low quality evidence).

They included 2 “Best Practices statements

  1. Any new class of antimicrobials or new antimicrobial combination developed for use in humans will be considered critically important for human medicine unless categorized otherwise by WHO. 
  2. Medically important antimicrobials that are not currently used in food production should not be used in the future in food production including in food-producing animals or plants.

One thing that stands out is the low quality of evidence. That doesn’t mean recommendations shouldn’t be made. Important decisions sometimes have to be made before the evidence is solid. However, we need to make sure the evidence follows. Much of what’s stated above is common sense, to a degree; however, sometimes things that make sense don’t actually turn out to be completely true. That’s one of the reasons CANresist is being developed, to help get the evidence and help translate both best practice and evidence based guidelines into action.

cia2017 copy2.jpg

4 comments on “Reducing Antibiotic Use in Dairy Calves”

Reducing Antibiotic Use in Dairy Calves

This topic’s huge, and there’s always a risk of trying to oversimplify the problem or solutions.

However, some solutions for some issues might be fairly straightforward. Whether it’s on a farm, in a hospital or in a doctors office, there are situations where I think it’s widely accepted we don’t need to use antibiotics, yet for various reasons they still get used. Getting over those barriers sometimes requires a combination of medicine, behavioural science, communications, psychology, economics and a range of other fields. Sometimes, though, the answer seems fairly simple.

A paper published in The Veterinary Journal showed how use of a simple treatment algorithm designed to be used by farmers results in an 80% reduction in antibiotic use in diarrheic dairy calves, with no impact on calf health.

That’s just one condition in one species, but it shows that there are some “low hanging fruit” that we might be able to pick.

Reference: DE Gomez, LG Arroyo, Z Poljak, L Viel, JS Weese. Implementation of an algorithm for selection of antimicrobial therapy for diarrhoeic calves: impact on antimicrobial treatment rates, health and faecal microbiota.

1 copy