Equine Antibiotics: What They Are, How They Work, and Resistance
Beneath our noses, yet unseen by the naked eye, there is a war going on. And the enemy is crafty in its response. Daily, humans wage chemical warfare against an overwhelming population--bacteria. In normal circumstances, humans and other animals coexist with these abundant life forms. And importantly, commensal (one species benefits while the other is unaffected) bacteria carry out work for us and our horses, helping with food digestion, keeping skin invaders in check, and controlling overgrowth of pathogens. But not all bacteria are good players; some can take hold of any organ system, creating infection and disease.
The arsenal of our chemical warfare relies on a mighty weapon--antimicrobial drugs (AMD), which are drugs or chemicals capable of killing or inhibiting growth of microorganisms. Of these substances, antibiotics have been a formidable weapon for over a century in the war against pathogenic bacteria. But antibiotics alone cannot vanquish bacterial invaders entirely; for complete resolution of infection, an animal's native immune system plays a crucial defensive role.
How Antibiotics Work
While antimicrobials derived from plants, bark, or molds have been used for thousands of years to combat infection, it wasn't until the 20th century that usage became common. "Antibiotic" originally described a substance derived from microorganisms that was able to antagonize growth of other microorganisms--a process known as antibiosis. It was Louis Pasteur who noted, "If we could intervene in the antagonism observed between some bacteria, it would offer 'perhaps the greatest hopes for therapeutics.' " If he could only have foreseen the extent to which the future would satisfy his objective!
Also at our disposal in the modern world are semisynthetic antibiotics, which are derived from compounds found in nature, but chemically modified, and totally synthetic antibiotics. Regardless of their source, antibiotics work on bacteria by either killing them (bactericidal) or impairing their growth (bacteriostatic). Optimum antibiotic kill depends on active cell division and growth of the pathogens. Bacteriostatic antibiotics hamper bacterial proliferation, thereby relying on the host's immune system to overwhelm and kill bacteria.
Because of the obvious results achieved with antimicrobials, a normal response in the face of an infection is to reach for antibiotics to disarm these infective organisms. But such a casual approach does not account for the myriad ways that bacteria react to this chemical pressure.
The Fight Back
Bacteria respond to selective pressures of antibiotics by developing ways to resist the effects of these miracle drugs. Every time an animal or human receives antibiotic therapy, drug exposure stimulates bacterial ability to evade the chemical effects.
The American College of Veterinary Internal Medicine (ACVIM) has issued a Consensus Statement co-authored by eight board-certified veterinarians regarding conscionable use of antibiotics in veterinary medicine. This statement explains the development of resistance mutations: "Because of the large number of bacteria produced during replication and the short generation interval, mutation is a common event. Although most mutations are likely detrimental to the organism, by random chance a mutation can develop that provides selective advantage to bacteria exposed to antimicrobial drugs, which therefore favors survival of strains less susceptible to the antimicrobial drug."
In addition, resistant bacteria no longer have to compete for space and nutrients, so their propagation improves.
These resistant bacteria the ACVIM co-authors mention are "selected" to survive and multiply, passing this genetic survival trait on to future bacterial generations. Such genes might also transfer between bacteria, in a process that leads to what is termed plasmid-mediated resistance. The ACVIM veterinarians make a daunting point: "Because of the ability for genetic elements to transfer among bacteria, and for bacteria to be exchanged between animals of the same or different species, it is theoretically possible for resistance to emerge in bacterial populations in animals that have never been exposed to antimicrobial drugs."
Selective pressure varies depending on choice of antibiotic, number of animals treated, the interval of dosing, route of administration, and length of treatment. With this in mind, the resounding outcry from the medical community (both human and veterinary) is to limit antibiotic use to situations where it's necessary.
Inappropriate Antibiotic Use
Harold McKenzie III, DVM, MS, Dipl. ACVIM, associate professor of medicine at Virginia Tech's Marion duPont Scott Equine Medical Center, represents the American Association of Equine Practitioners as a member of the American Veterinary Medical Association's committee to develop policy on antimicrobial drugs and resistance. He remarks on inappropriate antibiotic use: "There are situations where horses receive antibiotics when they don't need them, such as treating a horse with a respiratory virus (rhinopneumonitis or influenza) with antibiotics."
Attempts to manage viral infections with antibiotics are fruitless--antibiotics do not impact viruses in any way, and such inappropriate use creates unnecessary opportunity for antibiotic resistance to develop.
He continues, "Antibiotics may also be misused when treating nebulous disease processes where diagnosis is based only on poorly defined clinical signs or upon interpretation of imprecise diagnostic tests."
Yet another inappropriate use of antibiotics, McKenzie reports, is treatment of every horse on a farm, whether sick or not, because endemic exposure or disease is suspected.
"Another big problem arises when owners use over-the-counter antibiotics and a veterinarian is not involved in the diagnosis of the condition being treated or in recommending what antibiotics to use or how to use them." He emphasizes, "A veterinarian should always be involved in the decision-making process regarding the use of antibiotics."
He describes additional consequences of inappropriate antibiotic use or overuse that leads to microbial resistance: "We may be forced to use drugs that are typically reserved for second- or third-line (i.e., more serious) therapy. Many of these drugs are not intended for equine use, or may only be available as human drugs, resulting in substantially greater expense of treatment. Duration of treatment may be prolonged as well, with increased expense."
He adds, "Some medications may be toxic; for example, aminoglycosides (gentamicin, amikacin) can be toxic to the kidneys. Also, the risk of secondary effects, like antimicrobial-associated diarrhea (or colitis), is real and accompanies the use of any antibiotic. This complication can be severe and even fatal."
Strategies for Proper Use
Consult your veterinarian before reaching in your first aid kit for a bottle of antibiotics to treat your horse. Following a clinical exam, your veterinarian can determine if such therapy is justified and select the most effective antimicrobial drug; proper dosing interval, duration, and route of administration; as well as maintain concise medical records. Veterinary guidance also prevents improper use of expired antimicrobials or improper dosing.
For a problem that fails to resolve with therapy, rather than continuing on a prolonged course of an antimicrobial drug that is not working, your practitioner should step back and figure out why.
Therapy might fail because of bacterial resistance, but other reasons preclude successful treatment, such as:
- Poor owner compliance in administering proper amount, dosing interval, and duration;
- Insufficient prescribed dose or duration of treatment;
- Inappropriately prescribed antibiotic or the wrong diagnosis;
- Failure of the antibiotic to reach the infected site;
- Failure of the horse to mount a sufficient response to complement antibiotic action; or
- Antibiotic inactivation by feed ingredients or drug combinations.
Generally, horse owners assume that it is best to administer the widest-spectrum antibiotic to combat an infection, but in reality, a narrower spectrum lessens the possibility of developing resistance factors. There is an optimal approach to determining which antibiotic to use. McKenzie explains, "First one must consider the most likely type of organism involved in the infection, as this dictates the type of therapy used. Sometimes we make an educated 'guess' based on obvious clinical signs, like those seen with a strangles infection (Streptococcus equi)."
Yet he urges further diagnostic testing to determine the exact type of organism. This involves running a bacterial culture and sensitivity profile in the laboratory using a specimen taken from a wound, nasopharyngeal swab, tracheal wash, joint aspirate, abdominocentesis (belly tap), pleurocentesis (thoracic tap), or spinal tap.
He notes, "Gram staining of the sample allows us to visualize bacteria under the microscope to characterize infectious agents into broad classes (Gram-negative or Gram-positive bacteria). In addition, bacterial culture identifies the specific organism(s) and allows sensitivity testing regarding susceptibility to antimicrobials."
This scientific approach allows the vet to select the most appropriate antimicrobial regimen, fueling rapid resolution of an infection, while sparing the commensal bacteria that are doing no harm. Rapid resolution of an infection minimizes opportunities for resistance to develop.
McKenzie notes that a vet should choose an antibiotic administration route that will treat the horse most effectively. "Most antimicrobial drugs we use are labeled for use in animals, but just not always for horses, hence they are used 'extra-label.' "
He explains further, "Some antibiotics labeled for horses may be used in an extra-label manner, such as administration by a different route than the label specifies. One example is gentamicin, an antibiotic labeled for local intrauterine use that is often administered intravenously or intramuscularly for systemic effect."
Whether an antibiotic is given by an oral, intravenous, or intramuscular route, McKenzie describes its fate once in the body: "The liver eliminates many antibiotics, and either the intact drug or potentially active metabolites produced by the liver can end up in the intestine even if a drug is delivered by injection. Urinary and fecal elimination of antimicrobial drugs can result in substantial environmental contamination (potentially killing insects, soil inhabitants, water organisms, etc.)."
An Ounce of Prevention ...
This age-old adage couldn't be more apt when considering how to curtail the use of antibiotics. McKenzie urges owners and vets to use strategies designed to improve general horse health, several of which capitalize on prevention as the best cure: "All new introductions to a herd should be quarantined for at least two weeks to prevent spread of infectious disease; this minimizes the need for antimicrobial use."
Authors stress in the ACVIM Consensus Statement, "It is important for a horse owner to follow a veterinarian's recommendations regarding biosecurity measures to limit risk and spread of infectious disease." This includes routine vaccination to control viral disease, since secondary bacterial infections could follow a viral infection, thereby necessitating antibiotics.
McKenzie cites an example of dusty and overcrowded environments posing an increased risk to foals for developing rhodococcal bacterial pneumonia. He says, "Overuse of prophylactic antibiotics carries the risk of encouraging the development of resistance. For rhodococcal pneumonia, (use of) prophylactic azithromycin in foals may become widespread as cases begin to occur on a farm."
He explains that while this treatment strategy might be effective in reducing the number of foals that develop clinical Rhodococcus infections, it might also contribute to development of antimicrobial resistance on the farm, potentially decreasing effectiveness of the antimicrobial drugs used to treat those same infections.
He recommends, in this case, using simple management techniques to decrease dust and overcrowding, as it might be effective in minimizing infection risk without the veterinarian having to resort to antibiotic prophylaxis.
Similar management approaches are useful to prevent many equine bacteria-related illnesses. "In a hospital environment," McKenzie comments, "biosecurity measures are critical in preventing spread of infectious disease by limiting the exposure of susceptible individuals to infectious organisms." He notes that similarly, on the farm, handlers can use simple barrier procedures, including wearing gloves and separate clothing when dealing with infected horses and confining sick animals in a separate building. These methods can prevent contamination of common pastures or turnout lots.
Writers of the Consensus Statement urge owners to recognize that "wise, conservative use of antimicrobial drugs requires a sophisticated, integrated understanding of preventive medicine, internal medicine, microbiology, and pharmacology, as well as a thorough understanding of animal management." They note, "Veterinarians are uniquely trained to provide expertise in these disciplines. Therefore, to promote judicious use, antimicrobial drugs should only be used in animals under the direction of a veterinarian."
Just as importantly, owners can implement practical management and biosecurity strategies invaluable for preventing injury and infection, thereby avoiding the need for antibiotics in the first place.
About the Author
Nancy S. Loving, DVM, owns Loving Equine Clinic in Boulder, Colorado, and has a special interest in managing the care of sport horses. Her book, All Horse Systems Go, is a comprehensive veterinary care and conditioning resource in full color that covers all facets of horse care. She has also authored the books Go the Distance as a resource for endurance horse owners, Conformation and Performance, and First Aid for Horse and Rider in addition to many veterinary articles for both horse owner and professional audiences.
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