penicillin, any of a group of chemically similar substances obtained from molds of the genus Penicillium that were the first antibiotic agents to be used successfully in the treatment of bacterial infections in humans. The antagonistic effect of penicillin on bacteria was first observed by the Scottish biologist Sir Alexander Fleming in 1928. Although he recognized the therapeutic potential of penicillin, it was not until 1941 that a group of biologists working in England, including Oxford's Sir H. W. Florey and E. B. Chain, purified the substance and established its effectiveness against infectious organisms and its lack of toxicity to humans. The first successful treatment of a patient with penicillin occurred in New Haven, Conn., in 1942. Despite the development of hundreds of different antibiotics in recent decades, penicillin remains important in antibiotic therapy.

Small amounts of the antibiotic were first obtained from strains of the mold species P. notatum grown in fermentation bottles. During World War II need for the drug spurred development of better production methods; in the current method highly productive strains of Penicillium are grown in a cornsteep liquor medium in fermentation vats. The main form of penicillin produced by this method is benzylpenicillin, which, like all penicillins, is a derivative of 6-aminopenicillanic acid. Phenoxymethyl penicillin, which can be given orally because it is resistant to degradation by stomach acid, is produced by the species P. chrysogenum.


Penicillin is effective against many gram-positive bacteria (see Gram's stain), including those that cause syphilis, meningococcal meningitis, gas gangrene, pneumococcal pneumonia, and some staphylococcal and streptococcal infections. Most gram-negative bacteria are resistant to the antibiotic, but some, such as the bacteria that cause gonorrhea, are susceptible, and others are responsive to high penicillin concentrations or to only certain classes of penicillins. Tuberculosis bacteria, protozoans, viruses, and most fungi are not affected by penicillin. The class of penicillins that includes ampicillin and amoxicillin with clavulanate (Augmentin) is active against gram-positive and gram-negative bacteria such as Haemophilus influenzae and Escherichia coli. All penicillins act by interfering with synthesis of the cell wall.

Drug Resistance and Sensitivity

Use of penicillin is limited by the fact that, although it causes fewer side effects than many other antibiotics, it causes allergic sensitivity in many individuals, including skin reactions and allergic shock. In addition, many microorganisms have developed resistance to the penicillins, and serious hospital epidemics involving infants and surgical patients have been caused by penicillin-resistant staphylococci (see drug resistance). Some organisms are resistant because they produce an enzyme, penicillinase, that destroys the antibiotic. Synthetically produced penicillins such as methicillin and oxacillin have been developed that are not degraded by the penicillinase enzyme, but these new penicillins have no effect on bacteria that have developed resistance by other means, e.g., by altered cell wall structure. Other antibiotics, such as erythromycin, have become important in treating infections by microorganisms resistant to penicillin.

See E. Lax, The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle (2004).

The Columbia Encyclopedia, 6th ed. Copyright© 2018, The Columbia University Press.

Penicillin: Selected full-text books and articles

Launching the Antibiotic Era: Personal Accounts of the Discovery and Use of the First Antibiotics By Carol L. Moberg; Zanvil A. Cohn Rockefeller University Press, 1990
Librarian's tip: "Penicillin and Luck" begins on p. 31
The Flash of Genius By Alfred B. Garrett D. Van Nostrand, 1963
Librarian's tip: Chap. 7 "The Discovery of Penicillin"
Reason and Chance in Scientific Discovery By R. Taton; A. J. Pomerans Philosophical Library, 1957
Librarian's tip: "The Discovery of Penicillin" begins on p. 85
The Many Faces of Science: An Introduction to Scientists, Values, and Society By Leslie Stevenson; Henry Byerly Westview Press, 1995
Librarian's tip: "Fleming Playing Around with Germs and Molds" begins on p. 74
The Strange Case of the Spotted Mice and Other Classic Essays on Science By Peter Medawar Oxford University Press, 1996
Librarian's tip: Discussion of penicillin begins on p. 162
The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle By Stuart B. Levy Plenum Press, 1992
Librarian's tip: Chap. 1 "From Tragedy the Antibiotic Age is Born"
Antibiotics of Actinomycetes By Selman A. Waksman; Hubert A. Lechevalier Williams & Wilkins, vol.3, 1962
Librarian's tip: Chap. 2 "How Antibiotics Came to be Recognized"
To Light Such a Candle: Chapters in the History of Science and Technology By Keith J. Laidler Oxford University Press, 1998
Librarian's tip: "Penicillin and Vitamin B12" begins on p. 255
Magic Bullets, Lost Horizons: The Rise and Fall of Antibiotics By Sebastian G. B. Amyes Taylor & Francis, 2001
Librarian's tip: Chap. 2 "That's Funny"
Eureka! Stories of Scientific Discovery By Leslie Alan Horvitz Wiley, 2002
Librarian's tip: Chap. 7 "A Faint Shadow of its Former Self: Alexander Fleming and the Discovery of Penicillin"
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