Mats Troedsson, DVM, PhD, Dipl. ACT, DECAR, of the University of Kentucky’s Maxwell H. Gluck Equine Research Center, in Lexington, Kentucky, addressed antimicrobial resistance (AMR) from a reproduction standpoint during a presentation at the 2024 American Association of Equine Practitioners Convention, held Dec. 7-11, in Orlando, Florida. 

In theriogenology, veterinarians use antibiotics to not only treat infections but also improve reproductive efficiency in the absence of illness. They often administer antibiotics in post­breeding intrauterine infusions, following natural mating, during embryo transfer, and in semen extenders for artificial insemination without evidence of infection. 

Breeding-induced or physiologic endometritis (inflammation of the endometrium, or uterine lining) is predominately triggered by the presence of sperm, not bacteria, in the uterus. The purpose of this inflammatory reaction is to eliminate excess sperm and any contaminating bacteria and inflammatory products to allow a hospitable environment for the embryo.  

Recent data show, however, that almost 30% of mares clear the uterus of inflammation within six hours of breeding/insemination/embryo transfer, and approximately 85% of broodmares are resistant to persistent endometritis. 

“This emphasizes how effective the uterine defense mechanism is,” said Troedsson. 

For mares that can’t clear the inflammation, we need to ask why, he said. 

“We have previously shown that these mares have impaired myometrial contractility in response to inflammation due to accumulation of nitric oxide in the uterus as well as an imbalance between pro- and anti-inflammatory cytokines in response to breeding,” said Troedsson. “Predisposing factors can also include poor perineal conformation.” 

When a mare fails to clear bacteria from the uterus, antibiotics are indicated and should be selected based on culture and sensitivity results. Treatment should continue for three to five days and can be combined with uterine lavage if fluid is present. Note that mares diagnosed with bacterial endometritis will not be bred in the same cycle, so there is time to wait for the laboratory results to guide treatment, he said. 

In the case of treatment failures, consider the presence of resistant or dormant bacteria located in the deeper layers of the endometrium or endometrial glands or the presence of biofilm. 

“bActivate is a sterile growth medium that activates dormant Streptococcus zooepidemicus after being instilled in the uterus,” said Troedsson. “The uterus can be cultured the day after activation and the mare treated if the culture is positive. If the culture is negative, the uterus is clear.” This also works for other bacteria, he noted. 

In the case of persistent infectious endometritis that doesn’t respond to treatment, biofilms that evade both the immune system and antibiotics could be to blame.  

“Bacteria on the surface of the biofilm are exposed to sufficient concentrations of antibiotics, but reduced diffusion through the biofilm matrix leads to decreased concentration of antimicrobials within the biofilm community,” he explained. “This provides an excellent opportunity for bacteria to develop AMR. Further, genetic alterations associated with AMR are easily transmitted between bacteria in the biofilm, contributing to AMR.” 

To treat these infections, vets must first diagnose or suspect a biofilm, then break it down. “Biofilms are very difficult to diagnose in the field,” Troedsson said. “One potential way of diagnosing biofilms is to identify proteins or lipids specific to biofilms. If those molecules can be consistently recovered from mares with biofilms, an in vivo assay can be developed.” 

While veterinarians must treat endometritis using antibiotic therapy, Troedsson ­recommends treating breeding-induced endometritis with ecbolics, lavage, and possibly immune modulators, such as bacterial cell wall fractions (Settle), platelet-rich plasma, dexamethasone, or lactoferrin. 

“Antibiotics are not the first choice,” he stressed. “We know it is semen, not bacteria, causing the inflammation and subsequent uterine fluid.” 

Troedsson concluded by stating that while antimicrobials are valuable in equine reproduction for proven infections, using antibiotics to assist reproductive efficiency in horses with no health and well-being issues poses a challenge to equine practitioners. 

“We need alternatives to antibiotics, and decisions should be made based on scientific data rather than traditions and habits, such as routinely using antibiotics to flush mares 24 hours post-mating,” he said.