Multidrug resistance: A One Health approach

A recent study in the journal Antibiotics identified an increasing prevalence of multidrug resistant (MDR) Salmonella enterica isolated from cattle, highlighting the public health risk associated with widespread antibiotic use in humans and animals. Researchers characterized MDR S. enterica subspecies with biofilm-forming ability, some of which also demonstrated swarming and/or swimming motility along with one or more virulence genes. These bacteria were frequently resistant to treatment with critically important or last-resort drugs including macrolides (azithromycin and clindamycin), imipenem, and chloramphenicol, as well as other commonly used antibiotics. 

Yosra A. Helmy, DVM, MVSc, PhD, Associate Professor of One Health & Infectious Diseases in the Department of Veterinary Science at the University of Kentucky, was the lead investigator on the study, and she explained that the implications of this discovery extend far beyond cattle farms. 

“MDR Salmonella is a shared-risk pathogen, not a single-species problem,” Helmy said. “It can move from cattle to other food animals and even to our dogs, cats, and horses, then back to people, while sharing resistance genes along the way.” 

Mechanisms of antibiotic resistance 

The Salmonella spp. in question have developed multiple mechanisms by which they can evade antimicrobial destruction. 

Helmy explained that biofilms can complicate bacterial clearance by protecting them from exposure to antibiotics and changing the bacteria’s growth and metabolic rates. This results in lower antibiotic penetration rates and decreased bacteria killing as a result. But this is not true antibiotic resistance. 

According to Helmy, there are several factors that contribute to true antibiotic resistance in the Salmonella species she studied including: 

• mutations that code for β-lactamases that can inactivate cephalosporins 

• target mutations and plasmids that cause resistance to fluroquinolones  

• alterations in efflux pump expression and membrane permeability that increase the minimum inhibitory concentrations of antibiotics needed for antibiotics of all classes to be effective.  

“That’s why we pair anti-biofilm and anti-virulence tools with precise diagnostics and smart antibiotic use, so lifesaving drugs keep working for animals and people.”   

The primary cause of antibiotic resistance in cattle is the use of antibiotics on cattle farms, which tend to kill off susceptible bacteria and select for the proliferation of antibiotic-resistant organisms.  

But, Helmy said, antibiotic use on farms is not the only contributing factor. “Antibiotic resistance doesn’t respect fences,” she said. “Even when we use drugs responsibly in cattle, resistant bacteria and genes from human and companion-animal use can cycle through wastewater, soils, and wildlife and re-enter farm ecosystems.”  

Multidrug resistance in companion animals 

A study from 2021 measured rates of MDR Salmonella spp. in pet cats in urban settings in Romania. The results indicated that 18.82% of the cats tested were positive for one or more Salmonella serotypes, all of which demonstrated resistance to at least three different antibiotic drug classes. A positive association was noted between the presence of Salmonella spp. in fecal samples and consumption of raw food (especially raw meat).  

According to the study authors, other factors that affect Salmonella infections in cats include where cats live (urban vs rural), whether cats go outside, their owners’ food handling practices, and the time of year (bacteria grow faster in warmer weather and cats may have more exposure to undercooked meat when their owners are more likely to grill during warmer months).  

The Center for Disease Control and Prevention recommends against feeding raw pet foods or treats to dogs and cats, and their pet food safety website provides guidance on the safe handling of pet food and food containers to reduce the risk of food-borne illness for both pets and people.

 

Strategies to reduce antibiotic resistance 

Veterinary professionals in all parts of the industry can help to reduce future antibiotic resistance by practicing responsible antimicrobial stewardship and preventing infection spread through a combination of vaccination and proper biosecurity practices. 

“Stewardship is doing the simple things well,” Helmy explained. “Diagnose before you dose; right drug, right animal, right time, right duration, and pairing that with prevention and proven alternatives.” 

 This also means avoiding prophylactic or “just-in-case” antibiotic use and limiting perioperative antibiotic use to instances when evidence indicates it is appropriate. In cases of ear or skin infections, the use of approved topical antiseptics when indicated can reduce selection for antibiotic-resistant bacterial populations. Client education on appropriate use of antibiotics is important as well. 

Another example of stewardship is restricting the use of what Helmy refers to as “critically important” antibiotics (like vancomycin or imipenem) to hospital pharmacies that can carefully audit and control their use. Veterinary professionals can contribute bacterial isolates and data about their antimicrobial use to surveillance networks and research studies to uncover trends in microbial spread and drug resistance. 

Apart from antimicrobial stewardship, Helmy stressed that biosecurity measures such as isolation, hand hygiene, thorough cleaning and disinfection, and management of manure and water runoff can be hugely beneficial to reduce the likelihood of infection.  

Other strategies that may reduce the need for the use of antibiotics include vaccination and client education, Helmy said. Vaccines that protect against bacterial diseases such as Bordetella, leptospirosis, and Lyme disease may reduce the need for the use of antibiotics to treat cases of these diseases in dogs. The same can also be true for other animal species and humans and the vaccines that protect against bacterial infections pertinent to their species and exposure risks.  

The value of client education and a One Health approach 

Client education can help animal owners understand the ways they can reduce the risk of infectious disease in animals and for themselves. Helmy highlighted the importance of recommending against raw pet food diets and treats, both of which can serve as sources of infection to animals, humans, and the environment. Helping clients have realistic expectations around the appropriate use of antibiotics can also decrease misunderstanding and disappointment when they learn an antibiotic will not be prescribed for their animal.  

Additionally, Helmy pointed out that clients who seek care for their pets may also have contact with other animal species, including poultry, horses, and livestock. Teaching them about the importance of infectious disease control and prevention can help reduce disease spread between environments and between species. 

“Veterinarians are One Health ambassadors,” Helmy said. “Each culture you send, each narrow prescription you write, and each conversation you have about biosecurity or raw diets protects animals and also shields the family…and the broader community by slowing the spread of antibiotic resistance.” 

Further reading: 

The Use of Antibiotics and Antimicrobial Resistance in Veterinary Medicine, A Complex Phenomenon: A Narrative Review 

CDC: About Pet Food Safety

Photo credit: TopMicrobialStock/iStock via Getty Images 

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