Getting the Most From Antibiotics

Antibiotics have helped tame many feared infectious conditions and diseases. Here’s how judicious use, supplemented by common-sense management measures, can help ensure their continued effectiveness.
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Antibiotics have helped tame many feared infectious conditions and diseases. Here’s how judicious use, supplemented by common-sense management measures, can help ensure their continued effectiveness.

The bacteria in a horse’s environment can number in the billions per square inch. Fortunately, most are harmless, living in the soil and water and minding their own business. Others are do-gooders, living on a horses’ skin, in the respiratory system, and in the gastrointestinal tract, where they help safeguard and complement the immune system. In the gastrointestinal tract they aid in digestion as well. 

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Of course, not all bacteria are harmless. A small number of species, called pathogens, consistently cause disease if given a chance---when a horse’s structural defenses (his skin) and/or his cell and chemical defenses (his immune system) are breached. Also, normally benign bacteria sometimes become infectious if given the opportunity. For example, the coliform bacteria, which are found in manure, can get into a fresh wound within seconds, and given time, these organisms will set up shop and actively grow and reproduce. 

Your horse’s immune system is capable of taking on and neutralizing most bacterial infections on its own. But the inflammatory process can do collateral damage to healthy tissues. Plus, some infections and diseases can quickly grow out of control and produce devastating consequences, such as septic arthritis.

The best way to treat a bacterial infection is to physically get rid of the organisms and to change the environment where they are attempting to grow. For an open wound, this means cleaning the area, creating drainage, getting rid of dead tissue and perhaps applying local antiseptics. Most of the time, that’s all you’ll need to do. 

But sometimes, more help is needed. Fortunately, veterinarians can choose from a wide array of antibiotic drugs----agents that can kill bacteria (bactericidal) or impede their metabolism or multiplication (bacteriostatic) to assist in fighting infection.

In one sense, antibiotics have been around for centuries, if not many millennia. The use of plants, molds and other folk remedies that have an antibiotic effect most likely dates back to before recorded human history. In fact, our evolutionary cousins (apes and monkeys) as well as other animals are drawn to use antimicrobial agents in their environments.

Chemical antibiotic drugs have been available in modern medicine for only about 75 years---and they have changed history. Over the past seven decades, researchers have developed purified forms of naturally occurring antibacterials as well as synthetic versions of these agents. Along the way, more efficient ways of using these drugs have been devised, and new ways of combining different agents have also increased their efficacy. As a result, a number of once-feared diseases have been rendered curable. Infections that might once have disfigured, crippled and/or killed are often healed. 

Yet the threat remains. Wounds will always be vulnerable to bacterial infection, and there are diseases that may be controlled but not eradicated. We will forever need to practice good hygiene and take basic precautions to safeguard the health of our horses. Yet it’s good to know that our care measures can be complemented with powerful antibiotic drugs when needed.

Identifying the enemy
If you’re like me, when your horse gets sick you go into warrior mode. You call the veterinarian hoping that a magic bullet will quickly make your horse better. It’s never that easy.

To determine the best treatment for your horse’s problem, your veterinarian will first do a complete examination. He will listen to your horse’s heart, lungs and gut and get a rectal temperature. He may also draw blood to see if your horse has a high white blood count and a fibrinogen0 deficiency, telltale signs of systemic infection. If your horse’s history and signs point strongly toward a particular bacterial disease, such as Potomac horse fever, your veterinarian may go ahead and prescribe drugs known to be effective against the organism that causes it. 

However, if your horse is in real danger, and your veterinarian suspects a bacterial disease but is unsure of the specific organism involved and/or the location of the infection, he may at first prescribe a broad-spectrum antibiotic---one that is effective against many types of bacteria and that functions well in many areas and environments in the body. This allows treatment to start quickly, but it’s a shotgun approach, best used only when the enemy and location are not yet known and when the disease is severe. Broad-spectrum antibiotics are often effective, but they must be used with caution because, in addition to the pathogens, they can kill the beneficial bacteria in a horse’s gut, which may cause serious diarrhea.

Meanwhile, your veterinarian may collect blood, urine or other relevant body fluid samples to be tested for the presence of pathogenic bacteria. Veterinarians have known for a long time that the safest and most effective way to treat bacterial disease is to identify the exact organism involved, and then to deploy the antibiotic treatment that attacks it most effectively. Bacteria are identified in laboratory culture: A sample, usually from the patient’s site of infection, is cultivated in a special growth-promoting medium and environment. Bacteria are identified by the chemical reactions they uniquely perform and also by DNA testing. Often, these tests can identify the genus as well as the species of the organisms involved. In addition, other fluids may be analyzed to look for antibodies a horse has developed in response to exposure and infection.

Once the bacteria are identified, a sensitivity (or susceptibility) test is performed. The cultured organisms are exposed to a panel of antibiotics and subjected to other procedures to determine which drug or combination of drugs might be most effective against it. But this is only a starting point, because an antibiotic that works in a laboratory medium may be useless if your horse can’t tolerate it. Also, an antibiotic may be effective in the environment in the laboratory (in vitro), but environmental factors in the patient (in situ) may inhibit the agent’s effectiveness in the field. A good example is Rhodococcus equi, which causes foal pneumonia. The organism is sensitive to many antibiotics in the laboratory (in vitro), but it lives in the foal’s cells and is protected from many or most of these drugs.

Laboratory testing takes a few days, and meanwhile, one hopes, the horse has responded to the broad-spectrum antibiotic. With the information from the laboratory, no further treatment or a change in treatment may be selected, or your veterinarian may tailor the antibiotic to the specific disease and bacteria.

How the drugs work
The primary goal of using antibiotics is to kill or slow bacteria enough for the patient’s immune response to be sufficient to overcome the infection and regain control. The goal is not to kill all bacteria because often the concentrations of a drug required to do that are not safe for the patient and also may destroy “good” bacteria that are important in the horse’s defenses and functions.

The chemicals in these drugs may fatally injure the pathogens in a number of ways. Luckily, bacteria have a unique metabolism and structure that is different from those of mammalian cells, so it’s often possible to harm the pathogen while leaving the surrounding tissue unscathed. 

Most bacteria have an outer shell wall that is essential for the organism’s life and reproduction. The Gram stain is a simple test that reveals the nature of a bacterial cell wall. Gram-positive organisms such as Staphylococci and Streptococci stain purple. That means they have a simple cell wall made of cross-linked sugars and amino acids. Gram-negative bacteria like E. coli and salmonella stain pink because they have a more complex cell wall with an extra lipid layer that keeps the stain from taking hold.

Some drugs, such as penicillin, work by deforming normal bacterial cell walls by exposing them to compounds that cause defects. Some antibiotics work by interfering with the metabolic processes inside the bacteria. A few drugs hinder or stop the cells’ production of metabolic energy, which slows bacterial growth if not killing the organisms outright. Several antibiotics target protein production by attacking RNA (ribonucleic acid) and DNA (deoxyribonucleic acid) function, which is essential for growth, reproduction and metabolism. 

The environment where the anti-biotic is expected to work is important as well. Aerobic bacteria multiply best in the presence of oxygen, and anaerobic organisms are much happier in environments with little oxygen. These two types of bacteria have different metabolic pathways, and they don’t always react to antibiotics in the same way. Anaerobes are particularly problematic because they cause infections in puncture wounds, in deep tissue or in abscesses. There is poor blood flow and low oxygen levels in these areas. Not all antibiotics can work under those conditions, so your veterinarian must know if anaerobes are involved in your horse’s infection.

Special deliveries
Antibiotic drugs need to reach the infected site at concentrations high enough to do the job. If the infection is on or near the surface of the skin, this is easier. Scratches and wounds, for example, can often be readily treated just by cleaning the area and removing contaminated or devitalized tissue. A topical antibiotic may then be applied. For internal infections, the antibiotics must be delivered so that there is a therapeutic concentration in the blood and at the site of infection.

A number of antibiotics can be administered orally, in pills or pastes. Often, the medication must be given two or three times a day, for five days or a week at minimum. Sometimes that treatment needs to go on for months. Usually only one antibiotic is prescribed. In less common cases, two or even three at the same time may be necessary. Some antibiotics are not given orally---because they are destroyed in the gastrointestinal tract, they are not sufficiently absorbed through the gut wall, or the drug is cleared by the liver too rapidly. 

Drugs that are injected into muscle tissue (intramuscular) or infused directly into a blood vessel (intravenous) reach a higher concentration in the bloodstream and act more quickly. But administering antibiotics by these methods can cause irritation and, in some cases, risks serious
side effects. So your veterinarian will determine not only what is effective against the bacteria but what is safe for your horse.

Sometimes, more specialized delivery methods may be used to focus a drug treatment on a specific target. For example, leg infections may be treated with regional limb perfusion. In this method, a tourniquet is applied above the infection site, and then the antibiotic is infused into the blood supply of the limb. This essentially traps the drug in the area of infection. 

Some antibiotics collect in the urinary tract. They may not reach therapeutic levels in the bloodstream, but they can be 40 to 100 times more concentrated in the urinary tract and so may be more effective against pathogens in that specific location. 

Eye infections require specially formulated ophthalmic drugs that are safe to use in delicate ocular tissue. Mares with uterine infections and horses with joint infections can have antibiotics flushed directly into the site. Drugs that can’t be absorbed from the digestive tract may be effective against intestinal pathogens. When an infection occurs in an area with poor blood flow, methyl methacrylate beads can be used to time-release the drug in the affected area. Some specific antibiotics may also be formulated in lipid suspensions that release the drug from a single injection for three to five days. 

A particular treatment challenge is posed by systemic infections, which occur when a localized infection overwhelms a horse’s immune system, reaches the bloodstream and spreads to multiple organs. Drugs to treat these infections must be able to reach such disparate sites as the spinal fluid, joints and lungs. These patients may need intravenous antibiotics over a long period of time, which most likely will require a hospital stay. 

At the other end of the spectrum are those infections that are not good candidates for antibiotic treatment. Superficial infections, cuts and scrapes where the bacteria are confined to the skin can often be treated by simply cleaning them with antibacterial scrubs and keeping the wound protected and dry. Likewise, antibiotics may not be effective for abscesses, which form when the immune system tries to wall off an infection to keep it from spreading. The same barrier that keeps the bacteria contained can also prevent antibiotics from penetrating to the center of the infection. In hoof abscesses, for example, the nature of the abscess and the anatomy of the foot make it nearly impossible for antibiotics to reach therapeutic levels at the site of the infection. Pigeon fever’s distinctive swellings are caused by abscesses, as are the swollen lymph nodes of a strangles patient. In uncomplicated cases the veterinarian will most likely make draining these abscesses a priority before deciding if antibiotics are necessary. As hard as it is to watch a horse suffer through a hoof abscess or a case of strangles, once the abscesses are drained the infection most likely will resolve on its own without antibiotics.

Weapons in the arsenal
Although 18 major classes of antibacterials are used in veterinary medicine, only a limited number are known to be safe and effective for horses. Knowing a horse’s history and signs, and guided by laboratory results, a veterinarian will make the best choice, often prescribing one of these antibiotics.

Penicillins. One of the first antibiotics discovered, penicillin is a naturally occurring compound produced by the mold penicillium. There is a large family of synthetic and semisynthetic variations of penicillin available. Drugs in the penicillin family include ampicillin and amoxicillin. The penicillins are classed as beta-lactam antibiotics because of their molecular structure. They get substituted for the preferred bacterial cell wall compound and inhibit normal bacterial cell wall growth. Penicillin is poorly absorbed from the gut and is most often given via intramuscular or intravenous injection. Despite rising resistance to penicillin, it is still an effective drug.

Potentiated sulfonamides. The first fully synthetic class of antibiotics, sulfonamides are antimetabolites. Examples include trimethoprim-sulfamethoxazole, trimethoprim sulfadiazine, ormetoprim-sulfamethoxine and sulfadiazine pyrimethamine. Sulfonamides alone stop bacteria from growing (bacteriostatic) by blocking the folate pathway. Administering them in combination with certain diaminopyrimidines makes them somewhat able to kill bacteria (bactericidal).

Tetracyclines. Oxytetracycline and minocycline are examples of this class. They are generally considered bacteriostatic. They target protein synthesis. Oxytetracycline is administered intravenously while minocycline is given orally. Tetracyclines distribute extensively throughout the body and are the treatment of choice for Lyme disease (minocycline) and Potomac horse fever (oxytetracycline).

Metronidazole. Originally this drug was developed to treat protozoan0organisms. Metronidazole works by creating free0 radicals that break apart DNA. It’s most often given orally but can also be administered rectally. Metronidazole has great ability to infiltrate abscesses and go places most other antibiotics can’t. It is the drug of choice for anaerobic bacterial infections.

Chloramphenicol. This is a broad-spectrum, bacteriostatic antibiotic. Chloramphenicol is usually administered orally but it can also be included in topical ophthalmic solutions used to treat eye infections. Care must be taken by the person administering chloramphenicol because there have been documented cases of this drug causing aplastic anemia in people.

Gentamicin and amikacin. These aminoglycosides are useful for gram-negative infections. It was previously thought that they disrupt bacteria RNA, but now it is understood that they disrupt the gram-negative cell wall. Gentamicin and amikacin are commonly administered intravenously, intramuscularly, used in local and topical therapy, and in limb perfusion. 

Cephalosporins. These agents are a class of bactericidal antibiotics that includes ceftiofur, cefazolin, cefoxitin and many others. Beta-lactamase is a substance produced by bacteria that confers resistance to antibacterials like penicillin. Cephalosporins are bacterial beta-lactamase resistant and like penicillin work by disrupting the cell wall. Cephalosporins are classed by generation, each successive generation developed to counteract resistance and increase coverage of gram-negative organisms. These drugs are administered intramuscularly or intravenously and often used to treat respiratory infections.

Enrofloxacin. Like its relative ciprofloxacin, enrofloxacin is a quinolone, which acts by interfering with DNA coiling and therefore inhibits bacterial multiplication. Quinolones are bactericidal and are useful against many gram-negative organisms, especially intestinal pathogens, but are poorly active against anaerobes. They are best used intravenously in horses, since oral absorption is erratic. They are usually well tolerated. Quinolones can damage cartilage in the young of many species and are not recommended in young, growing horses.

Today, most bacterial infections are readily treated with antibiotics. But it’s important to do what we can to preserve the effectiveness of our antibiotic arsenal. With common-sense management measures and judicious use of these drugs, we can do our part to ensure that they continue to be a powerful weapon against bacterial illness for years to come.