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Reducing the need for antibiotics is key to preserving their use. Second of a six-part series.
April 24, 2017
“Go on and deny that antibiotic resistance is occurring in cattle and that we have any affect on it, but keep in mind the antibiotic groups you have today are likely the antibiotics you will have for the rest of your life,” says Mike Apley, a veterinarian and professor of production medicine and clinical pharmacology at Kansas State University’s College of Veterinary Medicine.
This single statement encapsulates much of the current challenge regarding antibiotic resistance in cattle, and how it’s perceived by some producers and veterinarians.
Apley’s’ not saying resistance is a rampant problem threatening doom to the cattle business. He’s saying that it’s becoming increasingly difficult to defend the use of antibiotics as a management tool.
“I want us to get a gut ache when we decide to use an antibiotic. It’s that important,” Apley tells his veterinary students. “Ideally, use antibiotics to treat sick cattle, but adopt practices that minimize the number of cattle that get sick.”
For producers and veterinarians, antibiotic resistance isn’t just about whether we do or don’t affect human antibiotic resistance, Apley explains. “It’s about preserving these valuable tools for our use 10 to 20 years down the road. We have to be good stewards of them, and that means doing everything we possibly can to make sure we only use them when absolutely necessary, and reducing the times they are necessary as much as possible.”
Apley points out that the last new antibiotic group released and approved for human or animal use — a member of that group is now used in food animals — was in 1978. Everything since then represents chemical modification, rather than new classes of antibiotics.
“Those modifications may help for a short time, but eventually they lose their effectiveness,” Apley says.
If you understand antibiotic resistance, then it hasn’t been explained to you adequately.
Apley frequently shares this observation — from Guy Loneragan, veterinary epidemiologist at Texas Tech University — with producers, because it sums up the fact that there are too many complexities to explain it simply within a species, let alone amid interaction between species and their environment.
In the simplest of terms, bacteria seek to build resistance to anything that imperils their survival. They’re masters of the process.
“Bacteria are like opossums; they live stupid and have a lot of offspring,” Apley says. “It’s not that the bacteria outsmart us, but it’s that there are so many offspring with so many different mutations that the ones that can survive multiply, and we have a new, adapted population. So when we create new versions of the same antibiotics that sometimes can outrun the adaptation process for awhile, we can see where the adaptation process begins again, and we end up at the same point.”
Consequently and unsurprisingly, you can find bacteria in cattle resistant to one or more classes of antibiotics. You can also find antibiotic resistance in humans and in the environment at large, of course. Connecting the dots of causation is another matter.
“As recently as 2000, we just didn’t see very much resistance in respiratory disease pathogens [BRD] in cattle,” Apley explains. “It still isn’t uniform in the population of BRD pathogens, but in the population of Mannheimia haemolytica isolates [a primary BRD pathogen] isolated in diagnostic laboratories, we have seen a dramatic shift over the last decade.”
Mannheimia haemolytica has gone from showing minimal resistance in the early 2000s to 75% to 80% of diagnostic laboratory isolates showing multidrug resistance today in some labs.
“We think these are primarily isolates from high-risk calves,” Apley says. “Some of the research would suggest that these aren’t even uniformly distributed throughout some groups of calves from which the isolate was isolated, but they weren’t being isolated from diagnostic submissions at this rate 10 years ago. Some of the resistance patterns have been associated with what is called an Integrative Conjugative Element, or ICE.”
Apley has logged lots of miles and hours on the front lines of the national debate surrounding antibiotic resistance. For instance, he was appointed by the Secretary of Health and Human Services to serve as a member of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria.
“The question from consumers, regulators and retailers isn’t about whether the antibiotics are effective for what we use them for, although we should be concerned about preserving them,” Apley explains. “The question is, ‘Why do you have to use antibiotics to prevent disease?’
“That question quickly gets into the safety and economical character of the U.S. food supply which, frankly, is utilized by those with multiple agendas. The question about why we use them is related to another one that we should be asking ourselves: Is modern agriculture dependent on antibiotics to prevent, control, and treat disease?”
Answering that question requires understanding antibiotic realities, rather than holding tight to myths. Apley’s short list of those myths goes like this:
Antibiotic resistance isn’t real. As mentioned earlier, resistance is growing for some organisms in some classes of cattle. Using an antibiotic, especially for extended periods, can modify the exposed bacterial population.
We can use antibiotics with no effect on the normal bacterial population of the gut, or on the pathogens which may eventually cause disease. “When we administer an antibiotic to cattle, we can change the flora in the gut and change the susceptibility pattern of pathogens,” Apley says. “The next question is how long this alteration lasts, and whether this modification has beneficial, detrimental, or a combination of these affects for cattle and for potential food-borne pathogens.”
Resistant bacteria don’t change treatment outcomes. “The fact is that resistance does affect treatment outcome and has been documented for many diseases,” Apley explains. He recognizes it can be difficult to obtain the statistically relevant number of treatment failures to compare susceptible and resistant pathogen outcomes. But, Apley emphasizes, “The only way an antibiotic can affect bacterial disease is by killing the bacterial pathogen or by inhibiting its growth. The resistant category is associated with the presence of resistance genes that make the antibiotic incapable of acting on the pathogen. It isn’t a lockstep relationship, but the trends are very clear.”
Antibiotics in humans and animals are unrelated. “Yes, they are related, even if they aren’t the exact same molecule,” Apley says. “One key exception is the ionophore group. Not only are they unrelated to anything used in human medicine, but they have a unique mechanism of action which has not been demonstrated to select for any type of human resistance, even through co-selection.”
Using drugs that have low importance in human medicine, such as tetracyclines, means there is no relationship to human medicine. “The issue isn’t how much the drugs are used in human medicine,” Apley explains. “Many of the multidrug resistant organisms in both veterinary and human medicine have genetics which are carried on transferable genetic elements, such as plasmids. “There are multiple plasmids which contain resistance genes to the most basic of antibiotics, such as the tetracyclines, and the highest-priority antibiotics, such as the fluoroquinolones and the cephalosporins. It is about co-selection within different bacterial populations, not just the specific antibiotic being used. Resistance selection pressure isn’t just about the antibiotic, it is also about the nature of the bacterial populations(s) being exposed, including existing resistance genetic elements and their association with each other.
All meat is antibiotic-free since we observe withdrawal times. “This couldn’t be further from the truth, and we need to stop this spin-doctoring,” Apley says. “Withdrawal times are about getting below a tolerance level, not getting to where there are no detectable residues. We need to safeguard our scientific credibility as our first priority.”
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