Antibiotics

Antibiotics (Greek anti, “against”; bios, “life”) are chemical compounds used to kill or inhibit the growth of infectious organisms. Originally the term antibiotic referred only to organic compounds, produced by bacteria or molds, that are toxic to other microorganisms. The term is now used loosely to include synthetic and semisynthetic organic compounds. Antibiotic refers generally to antibacterials; however, because the term is loosely defined, it is preferable to specify compounds as being antimalarials, antivirals, or antiprotozoals. All antibiotics share the property of selective toxicity: They are more toxic to an invading organism than they are to an animal or human host. Penicillin is the most well-known antibiotic and has been used to fight many infectious diseases, including syphilis, gonorrhea, tetanus, and scarlet fever. Another antibiotic, streptomycin, has been used to combat tuberculosis.

The HISTORY

Although the mechanisms of antibiotic action were not scientifically understood until the late 20th century, the principle of using organic compounds to fight infection has been known since ancient times. Crude plant extracts were used medicinally for centuries, and there is anecdotal evidence for the use of cheese molds for topical treatment of infection. The first observation of what would now be called an antibiotic effect was made in the 19th century by French chemist Louis Pasteur, who discovered that certain saprophytic bacteria can kill anthrax bacilli. In the first decade of the 20th century, German physician and chemist Paul Ehrlich began experimenting with the synthesis of organic compounds that would selectively attack an infecting organism without harming the host organism. His experiments led to the development, in 1909, of salvarsan, a synthetic compound containing arsenic, which exhibited selective action against spirochetes, the bacteria that cause syphilis. Salvarsan remained the only effective treatment for syphilis until the purification of penicillin in the 1940s. In the 1920s British bacteriologist Sir Alexander Fleming, who later discovered penicillin, found a substance called lysozyme in many bodily secretions, such as tears and sweat, and in certain other plant and animal substances. Lysozyme has some antimicrobial activity, but it is not clinically useful.

Penicillin, the archetype of antibiotics, is a derivative of the mold Penicillium notatum. Penicillin was discovered accidentally in 1928 by Fleming, who showed its effectiveness in laboratory cultures against many disease-producing bacteria. This discovery marked the beginning of the development of antibacterial compounds produced by living organisms. Penicillin in its original form could not be given by mouth because it was destroyed in the digestive tract and the preparations had too many impurities for injection. No progress was made until the outbreak of World War II stimulated renewed research and the Australian pathologist Sir Howard Florey and German-British biochemist Ernst Chain purified enough of the drug to show that it would protect mice from infection. Florey and Chain then used the purified penicillin on a human patient who had staphylococcal and streptococcal septicemia with multiple abscesses and osteomyelitis. The patient, gravely ill and near death, was given intravenous injections of a partly purified preparation of penicillin every three hours. Because so little was available, the patient's urine was collected each day, the penicillin was extracted from the urine and used again. After five days the patient's condition improved vastly. However, with each passage through the body, some penicillin was lost. Eventually the supply ran out and the patient died.

The first antibiotic to be used successfully in the treatment of human disease was tyrothricin, isolated from certain soil bacteria by American bacteriologist Rene Dubos in 1939. This substance is too toxic for general use, but it is employed in the external treatment of certain infections. Other antibiotics produced by a group of soil bacteria called actinomycetes have proved more successful. One of these, streptomycin, discovered in 1944 by American biologist Selman Waksman and his associates, was, in its time, the major treatment for tuberculosis.

Since antibiotics came into general use in the 1950s, they have transformed the patterns of disease and death. Many diseases that once headed the mortality tables—such as tuberculosis, pneumonia, and septicemia—now hold lower positions. Surgical procedures, too, have been improved enormously, because lengthy and complex operations can now be carried out without a prohibitively high risk of infection. Chemotherapy has also been used in the treatment or prevention of protozoal and fungal diseases, especially malaria, a major killer in economically developing nations (see Third World). Slow progress is being made in the chemotherapeutic treatment of viral diseases. New drugs have been developed and used to treat shingles (see herpes) and chicken pox. There is also a continuing effort to find a cure for acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV).