Guy H. Loneragan, PhD, said studying the unexplained drivers of antimicrobial resistance could help identify new interventions.
And Dr. Loneragan, an epidemiologist and professor at West Texas A&M University, said the tendency to brush aside unusual findings in studies combined with the complexity of resistance can lead to "black-and-white" arguments over whether all antimicrobial use is good or bad.
"When my students adopt a position very firmly, I remind them that, if you think you understand antimicrobial resistance, then it hasn't been explained to you properly," Dr. Loneragan said.
Dr. Loneragan was one of the presenters during Kansas State University's International Conference on the Use of Antimicrobials in Cattle Production, May 27-29. Speakers addressed a range of topics including how antimicrobial resistance and susceptibility are defined and identified, what has been proved, and what risks are posed by resistant bacteria.
According to Dr. Loneragan, attention to antimicrobial resistance should be focused on specific "bug-drug" combinations of the most concern. He also suggested that findings related to selection for resistance can be used against resistant bacteria.
"If we believe that selection for resistant strains has been our downfall, if we use our gray matter, then maybe selection for susceptible or less resistant strains could be our salvation," Dr. Loneragan said.
In discussing changes in ceftiofur resistance patterns after use of the antimicrobial is stopped, Dr. Loneragan talked about the fitness of organisms co-resistant to tetracycline and ceftiofur in comparison to those resistant only to tetracycline.
"If we use ceftiofur, we are selecting for the only ceftiofur-resistant subpopulations, and those are the ones that are co-resistant," Dr. Loneragan said. "But if we use tetracycline, then we've selected for the most fit population of tetracycline-resistant organisms, and that isn't the ones that are resistant to ceftiofur, but it's the ones that are tetracycline-only resistant."
Peter Silley, PhD, a microbiologist and a professor at the University of Bradford, U.K., said in his presentation he thinks little has been proved in terms of relationships between antimicrobial use in animals and human health. He pushed for caution in interpreting the relationships between use and resistance, while he accepted that a relationship does exist.
He acknowledged decisions have to be made even with incomplete data but said the decisions "need to be driven by data, rather than prejudice."
Dr. Silley also said a Chinese study of fluoroquinolone-resistant Salmonella strains indicated that resistant bacteria had lower virulence and pathogenicity. He said the authors of a study from Finland involving Escherichia coli and outpatient antimicrobial use found few associations between resistance and use.
"There are studies that are actually coming out now that maybe challenge something that perhaps we thought was the case," Dr. Silley said. "And I think we need to look at these studies quite carefully and compare them relative to some of the earlier work that had been done."
Dr. Silley cautioned that not all data are comparable, and he warned against thinking of resistance as a disease. He said it is an inevitable consequence of antimicrobial use, and prudent and appropriate use is critical.
"We need to move away from a simple view of causality as we actually try to get to grips with the overall ecology of antimicrobial resistance," Dr. Silley said. "And clearly, we're continuing to face new challenges, and I think we mustn't be burdened by old paradigms."
Dr. Frederick J. Angulo, deputy branch chief of the Centers for Disease Control and Prevention's Enteric Diseases Epidemiology Branch, said it is widely accepted that antimicrobials are useful in treating and preventing illness in animals, but the benefits of using them for feed efficiency or growth promotion are not well demonstrated. He said there was little evidence of production loss in Denmark, for example, when the country discontinued use of antimicrobials for growth promotion, although there was an increase in the focused use of antimicrobials to treat piglets.
"Antibiotic use in animals contributes to the spread of antibiotic resistance, and that can be transferred to humans," Dr. Angulo said. He added that there should not be much controversy about that spread.
Bacteria in food animals are subjected to selection pressure, and resistant strains are passed on through the food supply via treated animals, Dr. Angulo said. He cited ceftiofur as an example of an antimicrobial for which resistance trends were tracked as it was introduced, and he said resistance rose in animals and humans.
Dr. Angulo said that four potential consequences of the spread of antimicrobial resistance have been suggested and that, of these, the most difficult to prove is the creation of reservoirs of antimicrobial-resistant bacteria in humans that can flourish when antimicrobials are subsequently used to treat illnesses. Other potential consequences are increased infections, increased treatment failures, and increased severity of infections.
"There is scientific consensus that antibiotic use in food animals contributes to resistance in humans," Dr. Angulo said. "And there's increasing evidence that such resistance results in adverse human health consequences at the population level. Antibiotics are a finite and precious resource, and we need to promote prudent and judicious antibiotic use."
Dr. Christine N. Hoang, assistant director of the AVMA Scientific Activities Division, cautioned against drawing too many conclusions from trend data or using such data to justify implementing antimicrobial use bans. She said substantial evidence exists that such bans could harm animal health and welfare and adversely affect food safety.
"It's inappropriate to draw causal conclusions from trend data," Dr. Hoang said. "Trend data should really be used to trigger further investigation and further action."
Dr. Hoang said that because the public does not understand all uses of antimicrobials, some beneficial uses are viewed negatively.
She noted antimicrobials can be used to prevent and treat subclinical disease. Mass medication of flocks and herds can mitigate animal welfare concerns that would be associated with attempts to individually medicate every animal in a flock or herd during a disease outbreak. And antimicrobial use that increases feed efficiency lowers pollution from animal excrement.
Dr. Hoang said previous restrictions on antimicrobial use in animals have failed to demonstrate a substantial human health benefit or associated decline in the prevalence of resistant organisms in humans.
Dr. H. Morgan Scott, a professor of epidemiology at the Kansas State University College of Veterinary Medicine, suggested that increasing the sensitivity of surveillance systems could help to characterize strains drifting toward consistently prevalent resistance and to determine what is keeping resistance low among other bacteria. He said detecting low levels of resistance would not be useful in estimating the prevalence of resistance, but could be used as a guide for adopting effective and early mitigation procedures to preserve future agricultural use of specific products in specific hosts.
Dr. Michael D. Apley, the moderator and an organizer of the conference, said dialogue between groups with different stances on antimicrobial use illustrated how differently those groups perceive the amount of risk posed by antimicrobial use in animals and how much risk is acceptable. He said it is important to have the debates and discussions, and if he were to organize another such conference, he would increase the time dedicated to group discussions.
Dr. Apley said he hopes human health advocacy group members will learn more about how, where, and why antimicrobials are used in cattle. And he hopes producers will bring more scientific fact to public discussions and explain how they use antimicrobials.
"I came away from this meeting convinced that there is a huge portion of the public that still wants to have meat in their diet, and our responsibility now is to produce those proteins in an ethical, humane, and efficient manner," Dr. Apley said.