Antibiotics

L. MEYER JONES.

ANTIBIOTICS are produced during the normal growth of many types of threadlike, soil-inhabiting micro-organisms. Antibiotics inhibit the growth of bacteria. that compete with the soil micro-organisms for the available foodstuffs.

Antibiotics have been isolated and purified for use to control disease-producing bacteria. Several hundred antibiotics have been isolated from various sources. Penicillin, dihydrostreptomycin (streptomycin), chloramphenicol, chlortetracycline, oxytetracycline, tetracycline, erythromycin, bacitracin, and neomycin are among the best known antibiotics.

The chemical and physical characteristics of antibiotics must be known and respected in order to use them with good results. The common antibiotics are light-colored, comparatively unstable, and moisture-absorbent powders.

The antibiotics are stable indefinitely as dry powders in evacuated containers. When exposed to the air, the powders and their water solutions largely decompose within 24 hours. Exceptions are tetracycline, which remains potent for 2 to 3 weeks in solution, and chloramphenicol, which resists boiling and wide variations in acidity.

The exact mode of action of antibiotics against bacteria is still unknown. Considerable evidence indicates that the antibiotics interfere with various steps in cellular metabolism vital to bacterial growth. The antibacterial activity of antibiotics is highest during the period of greatest bacterial multiplication. When present in adequate concentration, antibiotics kill bacteria, but lower concentrations only inhibit the growing organisms. Old cultures of bacteria beyond the stage of rapid growth show less response.

The administration of antibiotics to animals for the control of disease is ordinarily by intramuscular or occasionally intravenous injection. Antibiotics are invariably administered by injection in herbivorous animals because oral administration for the treatment of disease suppresses the important cellulose-splitting and vitamin-synthesizing bacteria normally present in the digestive tract.

The antibiotics can be administered orally in the nonherbivorous animals, such as the dog, cat, and nonruminating calf, but intramuscular injection seems to be more successful because it provides better absorption of the drug with no opportunity for disturbing the digestion.

Most antibiotics are absorbed readily following injection into the tissue. The simple antibiotic salts are absorbed to produce a maximum blood concentration within 30 minutes for penicillin and about 60 minutes for other antibiotics, such as dihydrostreptomycin and the tetracyclines (Aureomycin, Terramycin, tetracycline).

Slowly absorbed preparations of some antibiotics are available, so that the period of effective treatment following injection is much prolonged; that is, a therapeutic dose of one penicillin preparation is absorbed continuously for 3 days, whereas another is absorbed for nearly 3 weeks in smaller daily amounts.

When it is given orally in nonherbivorous animals, penicillin must be protected with an alkali against destruction by the secretion of the stomach. Even when protected, five times the intramuscular dose of penicillin must be administered orally to obtain equivalent blood levels. Erythromycin, which may be employed instead of penicillin, need not be given in excessive dosage,because it is absorbed adequately following oral administration. The tetracycline antibiotics and chloramphenicol are absorbed readily from the digestive tract. Only about 10 percent of an oral dose of streptomycin is absorbed into the blood stream. The rest of the dose remains in the digestive tract, where it inhibits many kinds of bacteria. Neomycin is also poorly absorbed and produces a high concentration in the feces.

Most antibiotics are distributed readily through the body (except the central nervous system) in concentrations adequate for the treatment of either systemic or local infections. Antibiotics diffuse into the central nervous system with difficulty, but excessively high concentrations in the blood stream promote diffusion also into the nerve tissues. chloramphenicol is superior to other antibiotics for treatment of infections of the central nervous system because it diffuses into the cerebrospinal fluid in a concentration approaching 75 percent of that found in the blood.

The blood level of an antibiotic is determined primarily by the balance between the rate of absorption and the rate of excretion. Antibacterial levels of antibiotics persist in the tissues beyond the disappearance of the antibiotics in detectable levels from the blood stream.

Antibiotics absorbed into the blood are excreted primarily through the kidneys. Detectable amounts may be eliminated in other secretions of the body, particularly the bile. Antibiotics that are not absorbed from the digestive tract following administration by mouth are eliminated in the feces.

One of the greatest difficulties in the early use of penicillin arose from the rapid elimination of the antibiotic by the kidneys. It was unwise to delay the excretion of penicillin by altering the function of the kidneys, so the activity of a therapeutic dose of penicillin was prolonged by delaying its absorption following intramuscular injection.

Dihydrostreptomycin, chloramphenicol, and the tetracycline antibiotics are not excreted by the kidneys as rapidly as penicillin and are active in the tissues in antibacterial concentration for periods up to 24 hours. chloramphenicol is split into excretion products by the liver. A small amount of chloramphenicol plus large amounts of the split products are eliminated in the urine and in the bile. High concentrations of chloramphenicol, streptomycin, neomycin, and bacitracin are found in the feces following oral administration.

THE TOXICITY of antibiotics to an individual animal is generally low when it is properly employed. The relatively low toxic activity combined with relatively high antibacterial activity has made the antibiotics one of the most important groups of therapeutic drugs now available to combat infectious disease organisms.

Allergic reactions of an animal to penicillin or other antibiotics must be noted and further administration halted. When streptomycin is administered fora long time at high dosage, degeneration of the auditory nerve and the organ of equilibrium may occur.

With the recognition of the tendency for bacterial pathogens to become streptomycin-resistant during prolonged therapy, the duration of treatment has been markedly decreased; therefore, the probability that neurotoxicity will develop in animals during streptomycin therapy appears remote.

The toxicity from the tetracycline antibiotics is seldom serious except following the administration of an excessive dosage, which suppresses bacteria needed in the normal digestive processes.

Contrary to the experience in human medicine, toxic reactions to chloramphenicol have not been serious in animals. Blood-cell abnormalities have been noted in dogs and birds receiving chloramphenicol, however. Several antibiotics have been infused into the udder of the cow without causing signs of undue irritation or other toxicity. Not all antibiotics are free from toxcity however. The polymyxins, for example, have considerable renal toxicity, which definitely limits their use.

A disturbing and increasingly dangerous practice of giving antibiotics promiscuously for almost any and all kinds of sickness has become increasingly common in recent years when many antibiotics became generally available.

Some susceptible strains of disease-producing bacteria, especially staphylococci, may develop a total resistance because the antibiotics are improperly used. It has become apparent that when an antibiotic is used promiscuously in any given community or hospital, resistant strains of staphylococcic bacteria can be found in a significant portion of the animal or human population.

. The appearance of a disease germ during antibiotic treatment may be a major tragedy for a patient, but it will have little significance for other animals if the patient is properly isolated. Resistant germs, if they are to assume great significance, must be spread from a sick animal to other susceptible animals. Therefore the population of antibiotic-resistant disease germs in a herd or flock is directly proportional to the number of carrier animals and susceptible animals and to the frequency and intimacy of contact between the two groups.

Many persons have relied too much on antibiotics to control diseases. Under such circumstances it is natural that there should be concurrent laxness of hygiene and management of animal patients. Before we can take full advantage of antibiotic therapy, there must be renewed emphasis on isolation of the sick animal, with feeding and management measures that decrease the transmission of antibiotic-resistant organisms from patient to patient and from carrier to patient.

Antibiotics must be used cautiously, or their value will be lost. On the other hand, no patient should be deprived of the benefit of antibiotic therapy solely because of fear of inducing resistance in the disease germ.

L. MEYER JONES is professor of veterinary pharmacology in Iowa State College, He formerly was a fellow of the Research Council of the American Veterinary Medical Association and a Fulbright lecturer in pharmacology in Tierarztliche Hochschule in Vienna.