Penicillin

:For the Japanese rock band, see Penicillin (band).

History

Penicillin was originally isolated from the Penicillium chrysogenum (formerly Penicillium notatum) mould. The antibiotic effect was originally discovered by a young French medical student Ernest Duchesne studying Penicillium glaucum in 1896, but his discovery was ignored by the Institut Pasteur.

Related Topics:
Penicillium - Antibiotic - Ernest Duchesne - 1896 - Institut Pasteur

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It was serendipitously rediscovered in 1928 by Scottish scientist Alexander Fleming, who noticed a halo of inhibition of bacterial growth around a contaminant blue-green mould on a Staphylococcus culture. Fleming concluded that the mould was releasing a substance that was inhibiting bacterial growth. He grew a pure culture and discovered that the fungus was Penicillium notatum — he later named the bacterial inhibiting substance penicillin after the Penicillium notatum that released it. Fleming was convinced after conducting some more experiments that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931. It would prove to be the discovery that changed modern medicine. In 1939, Howard Walter Florey and a team of researchers at Oxford University made significant progress in showing Penicillin's in vivo ability to kill infectious bacteria. This eventually led to commercial production of penicillin and the belief that modern medicine has led the world in an era free of diseases.

Related Topics:
Serendipitously - 1928 - Alexander Fleming - Staphylococcus - Penicillium notatum - 1931 - 1939 - Howard Walter Florey - Oxford University - In vivo

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During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds amongst Allied forces. Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug necessitating frequent dosing. Penicillins are actively secreted and about 80% of a penicillin dose is cleared within three to four hours of administration. During those times it became common procedure to collect the urine from patients being treated so that the penicillin could be isolated and reused. (Silverthorn, 2004)

Related Topics:
World War II - Allied - Renal

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This was not a satisfactory solution, however, so researchers looked for a way to slow penicillin secretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for secretion such that the transporter would preferentially secrete the competitive inhibitor. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity. The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined. (Silverthorn, 2004) Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins. (Rossi, 2004)

Related Topics:
Uricosuric - Probenecid

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The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work. Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.

Related Topics:
Chemical structure - Dorothy Crowfoot Hodgkin - Ernst Boris Chain - Norman Heatley - 1945 - Nobel prize in medicine - Gram-positive

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