ANTIBIOTIC

chemical substance produced by a living organism, generally a microorganism, that is detrimental to other microorganisms. Although antibiotics are released naturally into the soil by bacteria and fungi, they did not come into worldwide prominence until the introduction of penicillin in 1941. Since then they have revolutionized the treatment of bacterial infections in humans and other animals. In 1928 Alexander Fleming noticed that colonies of bacteria growing on a germ culture medium had been unfavourably affected by a mold, Penicillium notatum, which had contaminated the culture. A decade later Ernst Chain, Howard Florey, and others isolated the ingredient responsible, penicillin, and showed that it was highly effective against many serious bacterial infections. Toward the end of the 1950s scientists then added various chemical groupings to the core of the penicillin molecule to generate semisynthetic versions. A range of penicillins is thus now available to treat diseases caused by such bacteria as staphylococci, streptococci, pneumococci, gonococci, and the spirochaetes of syphilis. Conspicuously unaffected by penicillin is the tubercle bacillus, but this organism proved to be highly sensitive to streptomycin, isolated from Streptomyces griseus in 1943. As well as being dramatically effective against tuberculosis, streptomycin also vanquishes many other bacteria, including the typhoid fever bacillus. Two other early discoveries were gramicidin and tyrocidin, made by bacteria of the genus Bacillus. Discovered in 1939 by Ren Dubos, they have proved to be valuable in treating surface infections but are too toxic for internal use. Other, more recently isolated, antibiotic drugs are the cephalosporins. Related to penicillins, they are produced by the mold Cephalosporium acremonium. A class of antibodies first developed in the 1960s, called quinolones, interrupt the replication of DNA (a crucial step in bacterial reproduction) and have proved useful in treating urinary-tract infections, infectious diarrhea, and various other infections involving such elements as bones and white blood cells. Many bacterial and, to a lesser extent, fungal infections can be treated by antibiotics; such drugs cannot treat viral infections, however. The principle governing the use of antibiotics is to ensure that the patient receives one to which the target bacterium is sensitive, at a high enough concentration to be effective (but not cause side effects), and for a sufficient length of time to ensure that the infection is totally eradicated. Antibiotics vary in their range of action. Some are highly specific. Others, such as the tetracyclines, act against a broad spectrum of different bacteria. These are particularly useful in combating mixed infections and in treating infections when there is no time to conduct sensitivity tests. Some semisynthetic penicillins and the quinolones can be taken orally, but most antibiotics must be given by intramuscular injection. A problem that has plagued antibiotic therapy from the earliest days is the resistance that bacteria can develop to the drugs. An antibiotic may kill virtually all the bacteria causing a disease in a patient, but a few bacteria that are genetically less vulnerable to the effects of the drug may survive. These go on to reproduce or to transfer their resistance to others of their species through processes of gene exchange. With their more vulnerable competitors wiped out or reduced in numbers by antibiotics, these resistant strains proliferate; the end result is bacterial infections in humans that are untreatable by one or even several of the antibiotics customarily effective in such cases. The indiscriminate and inexact use of antibiotics encourages the spread of such bacterial resistance.