Antibiotics are either injected, given orally, or applied to the skin in ointment form. Many, while potent anti-infective agents, also cause toxic side effects. Some, like penicillin, are highly allergenic and can cause skin rashes, shock, and other manifestations of allergic sensitivity. Others, such as the tetracyclines, cause major changes in the intestinal bacterial population and can result in superinfection by fungi and other microorganisms. Chloramphenicol, which is now restricted in use, produces severe blood diseases, and use of streptomycin can result in ear and kidney damage. Many antibiotics are less effective than formerly because antibiotic-resistant strains of microorganisms have emerged (see drug resistance).

Antibiotics have found wide nonmedical use. Some are used in animal husbandry, along with vitamin B₁₂, to enhance the weight gain of livestock. However, some authorities believe the addition of antibiotics to animal feeds is dangerous because continuous low exposure to the antibiotic can sensitize humans to the drug and make them unable to take the substance later for the treatment of infection. In addition low levels of antibiotics in animal feed encourage the emergence of antibiotic-resistant strains of microorganisms. Drug resistance has been shown to be carried by a genetic particle transmissible from one strain of microorganism to another, and the presence of low levels of antibiotics can actually cause an increase in the number of such particles in the bacterial population and increase the probability that such particles will be transferred to pathogenic, or disease-causing, strains. Antibiotics have also been used to treat plant diseases such as bacteria-caused infections in tomatoes, potatoes, and fruit trees. The substances are also used in experimental research.

The mass production of antibiotics began during World War II with streptomycin and penicillin. Now most antibiotics are produced by staged fermentations in which strains of microorganisms producing high yields are grown under optimum conditions in nutrient media in fermentation tanks holding several thousand gallons. The mold is strained out of the fermentation broth, and then the antibiotic is removed from the broth by filtration, precipitation, and other separation methods. In some cases new antibiotics are laboratory synthesized, while many antibiotics are produced by chemically modifying natural substances; many such derivatives are more effective than the natural substances against infecting organisms or are better absorbed by the body, e.g., some semisynthetic penicillins are effective against bacteria resistant to the parent substance.

Although for centuries preparations derived from living matter were applied to wounds to destroy infection, the fact that a microorganism is capable of destroying one of another species was not established until the latter half of the 19th cent. when Pasteur noted the antagonistic effect of other bacteria on the anthrax organism and pointed out that this action might be put to therapeutic use. Meanwhile the German chemist Paul Ehrlich developed the idea of selective toxicity: that certain chemicals that would be toxic to some organisms, e.g., infectious bacteria, would be harmless to other organisms, e.g., humans.

In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture, and in 1939 the American microbiologist René Dubos demonstrated that a soil bacterium was capable of decomposing the starchlike capsule of the pneumococcus bacterium, without which the pneumococcus is harmless and does not cause pneumonia. Dubos then found in the soil a microbe, Bacillus brevis, from which he obtained a product, tyrothricin, that was highly toxic to a wide range of bacteria. Tyrothricin, a mixture of the two peptides gramicidin and tyrocidine, was also found to be toxic to red blood and reproductive cells in humans but could be used to good effect when applied as an ointment on body surfaces. Penicillin was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin and a number of other antibiotics from Streptomyces griseus.

See also actinomycin, amphotericin B, ampicillin, lincomycin, neomycin, rifampin, and vancomycin.