PENICILLIN

one of the first and still one of the most widely used antibiotic agents, derived from the Penicillium mold. Alexander Fleming (later Sir Alexander Fleming) in 1928 first observed that colonies of the bacterium Staphylococcus aureus failed to grow in those areas of a culture that had been accidentally contaminated by the green mold Penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Howard Florey and Ernst Boris Chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use. The several kinds of penicillin synthesized by various species of the mold Penicillium may be divided into two classes: biosynthetic penicillins (those formed during the process of mold fermentation) and semisynthetic penicillins (those in which the structure of a chemical substance6-aminopenicillanic acidfound in all penicillins is altered in various ways). Because it is possible to change the characteristics of the antibiotic, different types of penicillin are produced for different therapeutic purposes. Benzylpenicillin, or penicillin G, is the only naturally occurring penicillin that is still used clinically. Because of its poor stability in acid, much of penicillin G is broken down as it passes through the stomach; as a result of this characteristic, it must be given by intramuscular injection, which limits its usefulness. Some of the semisynthetic penicillins are more acid-stable and so may be given as oral medication. All penicillins work in the same way, namely, by inhibiting the bacterial enzymes responsible for cell-wall synthesis and activating other enzymes to break down the organisms' protective walls; therefore, they are not effective against microorganisms that do not produce cell walls. Some strains of previously susceptible bacteria have developed a specific resistance to penicillin; these bacteria either produce penicillinases, enzymes that disrupt the internal structure of penicillin and thus destroy the antimicrobial action of the drug, or they lack cell-wall receptors for penicillin, greatly reducing the drug's ability to enter bacterial cells. Among the bacteria sensitive to penicillin are those that cause throat infections, pneumonia, spinal meningitis, gas gangrene, diphtheria, syphilis, and gonorrhea. The chief side effects of penicillin are allergic or hypersensitivity reactions, including skin rashes, hives, swelling, and anaphylaxis, or allergic shock. Milder symptoms may be treated with corticosteroids but usually are prevented by switching to alternative medications; anaphylactic shock, which can occur in previously sensitized individuals within seconds or minutes, may require immediate administration of epinephrine to end the life-threatening process.