Penicillin (sometimes abbreviated PCN) refers to a group of ?-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The name “penicillin” can also be used in reference to a specific member of the penicillin group. All penicillins possess the basic Penam Skeleton, which has the molecular formula R-C9H11N2O4S, where R is a variable side chain.
Contents
- 1 History
- 2 Developments from penicillin
- 3 Mode of action
- 4 Variants in clinical use
o 4.1 Benzathine benzylpenicillin
o 4.2 Benzylpenicillin (penicillin G)
o 4.3 Phenoxymethylpenicillin (penicillin V)
o 4.4 Procaine benzylpenicillin - 5 Semi-synthetic penicillins
o 5.1 Narrow spectrum penicillinase-resistant penicillins
o 5.2 Moderate spectrum penicillins
o 5.3 Extended Spectrum Penicillins
o 5.4 Penicillins with beta-lactamase inhibitors - 6 Adverse effects
o 6.1 Adverse drug reactions
o 6.2 Allergy/hypersensitivity - 7 See also
- 8 References
- 9 External links
[edit] History
The discovery of penicillin is usually attributed to Scottish scientist Alexander Fleming in 1928, though others had earlier noted the antibacterial effects of Penicillium. Fleming, at his laboratory in St. Mary’s Hospital (now one of Imperial College teaching hospitals) in London, noticed a halo of inhibition of bacterial growth around a contaminant blue-green mould on a Staphylococcus plate culture. Fleming concluded that the mould was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mould and discovered that it was a Penicillium mould, now known to be Penicillium chrysogenum. Fleming coined the term “penicillin” to describe the filtrate of a broth culture of the Penicillium mould. Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. He expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with mi
nimal toxicity compared to antiseptics of the day, but particularly noted its laboratory value in the isolation of “Bacillus influenzae” (now Haemophilus influenzae).[1] After further experiments, Fleming was convinced that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931, but restarted some clinical trials in 1934 and continued to try to get someone to purify it until 1940.
In 1939, Australian scientist Howard Walter Florey and a team of researchers (Ernst Boris Chain, A. D. Gardner, Norman Heatley, M. Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made significant progress in showing the in vivo bactericidal action of penicillin. Their attempts to treat humans failed due to insufficient volumes of penicillin, but they proved its harmlessness and effect in mice. Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford. On 1942-03-14 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.[2][3]
Penicillin was being mass-produced in 1944
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Penicillin was being mass-produced in 1944
During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds amongst Allied forces; saving an estimated 12-15% of lives. 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.[4]
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.[4]Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins.[5] survivers of the death
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. Alexander Fleming has also discovered that tears have bacteria killing cells in them which cause no physical damage to the body.
