Antibiotics


Most owners forget that antibiotics are drugs, and, if misused, they can cause short- and long-term problems for horses and, potentially, humans.
Growing up in an era of modern medicine, the availability of antibiotics has been taken for granted. How often have you been asked if you are taking antibiotics for a cough or a sniffle? How many times have you seen a horse being administered antibiotics for a nonspecific fever or for a relatively superficial wound?

Antibiotics have been impressive tools for improving health, yet they also pose one of the most pressing public health problems facing the medical community today. With increased antibiotic use comes increasing emergence of resistant strains of bacteria; such bacteria have developed ways to avoid being eliminated by drugs.

Some organisms that infect animals also infect people, and these bacteria make no distinction between types of mammalian tissue; to bacteria, it is a warm body with nutrients to support growth and multiplication of their numbers. And, similar antibiotics are used in many animal species and in people. The more exposure bacteria have to antibiotics, the more opportunities there are to develop drug resistance, with the potential for disastrous consequences: humans with serious infections can die, and in the veterinary world, there might be treatment failure or life-threatening diarrhea in horses.

Josie Traub-Dargatz, DVM, MS, Dipl. ACVIM, professor of equine medicine at Colorado State University's College of Veterinary Medicine and Biomedical Sciences in the Animal Population Health Institute, is dedicated to educating horse owners about the proper use of antibiotics. She remarks, "Antimicrobial drugs are critical in the treatment of bacterial infections in horses, and we need to think of them as tools to be taken care of just as we would take care of any valuable piece of equipment that we want to keep working for us. In order to use these tools most effectively, education is the key."

Prevention

Traub-Dargatz endorses a proactive disease-prevention approach: "Infection prevention strategies can be implemented that reduce, if not entirely eliminate, the need for some antimicrobial drug use. For example, we can promote biosecurity practices that emphasize strategies that limit risk of exposure along with a prophylactic vaccination program to protect against disease. A thorough examination should be performed on any horse that shows signs of being ill to identify if there is a bacterial infection that may require antimicrobial treatment. Early detection of ill horses should be followed with isolation and good hygiene on the premises to reduce spread of disease. Ensuring that foals receive adequate passive transfer is an effective strategy to prevent systemic infections that might require antibiotics. Neonatal foals must receive adequate transfer of antibodies from the colostrum to help protect them from infection, and owners should work with their veterinarian to have foals tested to be sure they have gotten adequate antibodies and, if not, then work on a plan for intervention."

Louise Southwood, BVSc, PhD, Dipl. ACVS, assistant professor of large animal emergency and critical care at the University of Pennsylvania's New Bolton Center, also urges veterinarians to implement strategies besides antimicrobials to curtail infection. She suggests, "Antimicrobials are not needed for minor superficial wounds and should never be used in place of appropriate wound cleansing and topical treatment. Use of antimicrobial drugs for deep wounds affecting bone and joints/tendon sheaths is, on the other hand, an important part of treatment. In appropriate cases, use of local antimicrobials may reduce the risk for selection of resistant bacteria in sites like the digestive tract that occur when antimicrobial drugs are given orally or by systemic injection." Local treatment includes regional limb perfusion through a vein or bone in an infected lower limb region, constant rate infusion delivery to a joint via an indwelling catheter, or implants such as antimicrobial- impregnated beads inserted into infected sites.

She notes the equine immune system deals with contamination and fights infection effectively, "and we should also focus on providing appropriate nutrition and other support for our sick equine patients."

Antibiotics in Veterinary Medicine

By definition, an antimicrobial is a substance that inhibits the growth of bacteria. Antibiotics are derived from living organisms, while antimicrobial drugs also include synthetic or combination medications that suppress bacterial growth. Just as there are many different types of bacteria, there are different antimicrobial drugs that possess properties that allow them to target specific microorganisms.

"In both veterinary medicine and human medicine, we have an obligation to use antimicrobial drugs judiciously and responsibly, administering these drugs where there is a clear indication for use and in situations where we believe treatment is likely to result in resolution of a bacterial infection," Traub-Dargatz says. This objective calls for evidence-based science rather than guesswork.

"The key to identifying the infection problem is in taking a good medical history on not only the individual horse, but on other horses in the facility as well as horses exposed to the ill horse," Traub-Dargatz emphasizes.

Follow this with a thorough physical examination and possibly collection of samples for diagnostic testing, she adds. This gives critical information to suggest if a bacterial infection exists, and if an antimicrobial drug is needed.

"In some patients," Traub-Dargatz says, "a veterinarian will recommend an antimicrobial drug based on past experience with similar-type infections; this is called empirical treatment. This approach is an accepted standard of care, as it allows for immediate initiation of treatment." Certain bacteria are more commonly associated with some diseases than others, and an antimicrobial drug can be selected empirically, based on the type of bacteria that's most likely causing the infection.

"However, if a patient fails to respond to the antimicrobial treatment, or if the animal has severe disease or is not a typical case, then material should be collected from the infection site with subsequent culture and sensitivity testing in a laboratory," Traub-Dargatz elaborates.

Southwood explains, "Different antimicrobial drugs are effective against different bacteria; therefore, bacterial culture and sensitivity testing are important to isolate the type of infecting bacteria, and to identify the best possible antimicrobial to suppress bacterial growth," she states.

"With increasing emergence of resistance to commonly used antimicrobial drugs, bacterial culture and sensitivity testing are becoming more and more important to treat accurately and to monitor antimicrobial drug resistance and sensitivity patterns," she concludes. You can't determine which bacteria are causing the infection by just examining the patient.

Traub-Dargatz says to accurately monitor change in antibiotic resistance patterns, it would be ideal if results from multiple laboratories or veterinary clinics could be collected and summarized. "However, funding to do this kind of research is difficult to attain," she states.

Drug Availability

"There are only a limited number of antimicrobial drugs approved for use in equine patients at the dose or route by which we use them," Traub-Dargatz explains. "However, veterinarians can prescribe the use of drugs by what is called 'for extra-label use' when there is no labeled drug that will work as well or better than the one prescribed for the medical condition. In addition, there must be an active veterinary-client-patient relationship that allows us to diagnose and treat the animal."

Veterinarians are limited in their choices of drugs labeled specifically for horse use. One reason is it's very costly for drug companies to research, develop, and complete the necessary approval process.

Some well-conducted studies of the behavior of various antimicrobial agents in horses have determined the duration of blood levels of the drug as well as the concentration achieved in various tissues. However, Traub-Dargatz points out that these studies are often conducted on healthy adult animals. She notes, "The drugs do not necessarily perform the same in ill or neonatal animals, so we don't always have all the information available that would allow us to most effectively dose the antimicrobial drug in all patients. Often we must use data that was generated in laboratory animals or humans."

Inappropriate Use?

Southwood explains why antimicrobial drugs might be "inappropriately used." She mentions antimicrobials are often reached for when there is a concern of a serious or life-threatening infection, and, similarly, their use has become something of a habit, especially since antimicrobials have been proven effective in preventing and treating bacterial infections. In addition, they are economical to use and readily available.

Southwood states that prolonged antimicrobial treatment is the most common inappropriate use; this has been documented in human hospitals, but there are no data for veterinary hospitals. She adds, "Another component is created by pressure from horse owners to treat with antimicrobial drugs to lower the risk of secondary infection, reduce recovery time, and in some cases to comply with stable management guidelines." This can lead to treating a virus-infected horse with antimicrobials, which are ineffective against viruses.

"Antimicrobial drugs are like any other drug," she notes. "They are very effective for treating disease, but there can be complications and consequences of misuse. Treating a horse with an antimicrobial drug just because it is easy, safe, and economical, without a sound clinical basis, is inappropriate. Equine owners should not begin treating a horse with antimicrobial drugs without first consulting their veterinarians, and owners need to become educated on the risks of using antimicrobial drugs in horses."

Southwood compares principles of antibiotic use in human medicine: "Compare the infant that attends day care that frequently has a runny nose and intermittent fever with the weanling horse that also has a runny nose and intermittent fever; we do not immediately treat the human infant with antimicrobial drugs (because the problem is most likely caused by a virus), but the weanling is often treated with a broad-spectrum oral antibiotic for seven to 10 days."

Prophylactic Use for Surgery

Southwood says antimicrobial drug prophylaxis for surgical procedures has probably had as big an impact as anything on improving patient survival and reducing postoperative complications. She says the favorable effects of antimicrobial drugs are achieved only if given within the two-hour window immediately before surgery. "If given postoperatively, the infection rate is no different to that when antimicrobials are not used," she says. "Antimicrobial drugs given more than two hours prior to making an incision are also not effective."

She stresses, however, "antimicrobial drugs should never replace aseptic and atraumatic surgical technique."

Traub-Dargatz says guidelines exist for using antimicrobial drugs based on the existing or likely contamination of a surgery site. Southwood expands on this: "Based on recommendations from human surgery, antimicrobial drugs are indicated in cases where the infection rate without antimicrobials is greater than 5%, such as in clean-contaminated, contaminated, and dirty procedures, when implants are used, or when infection would be devastating or life-threatening."

Traub-Dargatz explains that antimicrobial drugs are given prior to colic surgery because until the abdomen is visualized at surgery, it is difficult to know the severity of intestinal compromise or whether the bowel will need to be entered as part of the surgical intervention. Drugs should not be used as a substitute for good sterile technique during surgery.

Adverse Reactions and Resistance

Traub-Dargatz suggests the use of any drug or biologic product should be carefully considered and weighed against the risks for adverse reactions. Additionally, a growing concern is emerging antimicrobial drug-resistant bacteria in hospitals and in the community. "If a person or animal has a multidrug-resistant bacterial infection, there is a delay in treating with appropriate antimicrobial because the 'first-line' antimicrobial drugs are no longer effective," Southwood says. "This increases the death rate from serious infections."

In humans, mortality rates are higher when patients with multidrug-resistant bacterial infections receive ineffective antimicrobial drugs, as compared to such patients treated with antimicrobials that are effective against nonresistant bacteria.

What are the practices that are most likely to cause resistance? "It is possible that if we do not use the most appropriate antimicrobial or don't use it for an adequate duration, then we might see treatment failure, not necessarily due to development of resistance per se," says Traub-Dargatz. "We strive to use an antimicrobial drug that is likely to resolve the infection, while reserving use of the most potent antimicrobial drugs for those patients with demonstrated multidrug-resistant infections."

Traub-Dargatz describes the potential for antibiotic resistance: "With antimicrobial drug use we risk selecting for bacteria that are resistant or are becoming resistant to the drug used in treatment. Some bacteria are very adaptable and have multiple ways to survive exposure to an antimicrobial drug. Some bacteria are inherently resistant to certain antimicrobial drugs because of the mechanism by which the drug inhibits bacterial growth or kills that type of bacteria. Or, bacteria develop methods to resist the influence of the antimicrobial."

In addition, she points out that disinfectants are also considered antimicrobials, by definition. "We are learning that there may be cross-resistance between some disinfectants and antibiotics (meaning use of the disinfectant in an environment renders the antibiotic ineffective in horses kept there)!" she notes. "Another area to explore is whether the use of disinfectants in hospitals promotes resistance to antibiotics."

She says veterinarians have to keep in mind that "other bacteria beyond those we are trying to treat are also exposed to the drug. Thus, we can select for resistance in what we call 'bystander bacteria,' for example, those that live in the digestive tract."

It is just as important to administer the antimicrobial at the optimal dose, at appropriate dosing intervals, for the appropriate time (depending on the severity of the infection and response to treatment), and by an appropriate route.

Southwood says we don't know the appropriate equine doses for all of the therapeutic and prophylactic antimicrobials available. "In human medicine, it is becoming apparent that the duration of therapeutic antimicrobial drug use can be much shorter than that previously used," she says. Patient and physician education and clinical trials have led to improvements in human drug use. Veterinarians hope more funding and clinical studies will allow the same improvements for horses.

Take-Home Message

"Historically, people have had the attitude that giving an antibiotic might help and can't do any harm," notes Traub- Dargatz. "The more we know about antimicrobial drugs (or any drug), the more we find potential for adverse outcomes from their use. Therefore, in deciding what is best for the patient, we must consider the potential for harm along with the potential for benefit." In addition to implementing infection prevention strategies, all aspects of drug use should be taken into account when reaching for this valuable tool in the fight against infection.

About the Author

Nancy S. Loving, DVM

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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