Difference between revisions of "Penicillin" - New World Encyclopedia

From New World Encyclopedia
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[[Image:Penicillin-core.png|thumb|200px|Penicillin structure]]
 
[[Image:Penicillin-core.png|thumb|200px|Penicillin structure]]
'''Penicillin''' (sometimes abbreviated '''PCN''') refers to a group of β-lactam antibiotics used in the treatment of [[Bacteria|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-C<sub>9</sub>H<sub>11</sub>N<sub>2</sub>O<sub>4</sub>S, where R is a variable side chain.
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[[Image:Penicillin 3D Model.png|thumb|Penicillin]]
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'''Penicillin''' (sometimes abbreviated '''PCN''') refers to a group of β-lactam [[antibiotic]]s used in the treatment of [[Bacteria|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 of [[fungus|fungi]], such as the mold ''Penicillium chrysogenum''. All penicillins possess the basic Penam Skeleton, which has the molecular formula R-C<sub>9</sub>H<sub>11</sub>N<sub>2</sub>O<sub>4</sub>S, where R is a variable side chain.
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It is estimated that penicillin has saved at least 200 million lives since its first use as a medicine in 1942.
 +
 
  
 
==History==
 
==History==
The serendipitous discovery of penicillin is usually attributed to [[Scotland|Scottish]] scientist Alexander Fleming, though others had earlier noted the antibacterial effects of ''Penicillium.'' (Penicillium is a member of the deuteromycetes, fungi with no known sexual state. As it grows, it gives off the liquid referred to as penicillin.) In 1928 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 mold on a ''Staphylococcus'' plate culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a ''Penicillium'' mold, now known to be ''Penicillium chrysogenum''. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the ''Penicillium'' mold. Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. (Gram-positive (as opposed to gram-negative) refers to the characteristic blue-violet color reaction of certain types of bacteria in what is called the Gram-staining procedure. A major feature of gram-positive bacteria is the high percentage of peptidoglycan (sugar + amino acid molecule) in the cell wall.) Fleming expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, but particularly noted its laboratory value in the isolation of "''Bacillus influenzae''" (now ''Haemophilus influenzae'').<!--
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[[Image:SEM_bread_mold_(1200x).jpg|thumb|Penicillium fungus, ancient remedy]]
  —><ref name="Fleming1929">{{cite journal | author=Fleming A. | title=On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of ''B. influenzæ''. | journal=Br J Exp Pathol | year=1929 | volume=10 | issue=31 | pages=226–36}}</ref>
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 +
The serendipitous discovery of penicillin is usually attributed to [[Scotland|Scottish]] scientist Alexander Fleming, though others had earlier noted the antibacterial effects of ''Penicillium.'' (Penicillium is a member of the deuteromycetes, fungi with no known sexual state. As it grows, it gives off the liquid referred to as penicillin.) Many ancient cultures, including the ancient Greeks and ancient Chinese, already used molds and other plants to treat infection. This worked because some molds produce antibiotic substances. However, they couldn't distinguish or distill the active component in the molds. There also are many old remedies where mould is involved. In Serbia and in Greece, moldy bread was a traditional treatment for wounds and infections.
 +
 
 +
Sir John Scott Burdon-Sanderson, who started out at St. Mary's Hospital 1852-1858 and as lecturer there 1854-1862, observed in 1870 that culture fluid covered with mold would produce no bacteria. In 1871, Joseph Lister, an English surgeon and the father of modern antisepsis, described that urine samples contaminated with moud did not allow the growth of bacteria and he also described the antibacterial action on human tissue on what he called ''Penicillium Glaucum''. A nurse at Kings College Hospital, whose wounds did not respond to any antiseptic, was then given another substance which cured her, and Lister's registrar informed her that it was called Penicillium. Louis Pasteur and Jules Francois Joubert in 1877 had observed that cultures of the anthrax bacilli, when contaminated with molds, became inhibited. Some references say that Pasteur identified the strain as ''Penicillium notatum''.
 +
 
 +
In 1928, 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 mold on a ''Staphylococcus'' plate culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a ''Penicillium'' mold, now known to be ''Penicillium chrysogenum'' (also known as ''P. notatum''). Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the ''Penicillium'' mold. Even in these early stages, penicillin was found to be most effective against [[bacteria|Gram-positive]] bacteria, and ineffective against Gram-negative organisms and fungi. (Gram-positive (as opposed to gram-negative) refers to the characteristic blue-violet color reaction of certain types of bacteria in what is called the Gram-staining procedure. A major feature of gram-positive bacteria is the high percentage of peptidoglycan (sugar + amino acid molecule) in the cell wall.) Fleming expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, but particularly noted its laboratory value in the isolation of "''Bacillus influenzae''" (now ''Haemophilus influenzae'') (Fleming 1929).
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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 find someone to purify it until 1940.
 
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 find 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. (Bactericidal refers to inhibition of the growth or activity of bacteria, thus the prevention of infection.) 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 March 14, 1942 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.<!--
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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. (Bactericidal refers to inhibition of the growth or activity of bacteria, thus the prevention of infection.) 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 March 14, 1942 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin (Saxon 1999, Krauss 1999).<!--
  —><ref>{{cite news | author=Saxon, W. | url=http://www.wellesley.edu/Chemistry/Chem101/antibiotics/obit-a-miller.html | title=Anne Miller, 90, first patient who was saved by penicillin | publisher=The New York Times | date=[[1999-06-09]]}}</ref><!--
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  —><ref>{{cite web | author=Krauss K, editor | title=Yale-New Haven Hospital Annual Report | url=http://www.ynhh.org/general/annreport/ynhh99ar.pdf | format=PDF | year=1999 | publisher=Yale-New Haven Hospital | location=New Haven}}</ref>
 
 
 
 
[[Image:PenicillinPSA.gif|thumb|right|300px|Penicillin was being mass-produced in 1944]]
 
[[Image:PenicillinPSA.gif|thumb|right|300px|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. 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.<!--
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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).  
  —><ref name="Silverthorn2004">{{cite book | author=Silverthorn, DU. | title=Human physiology: an integrated approach. | edithion=3rd ed. | location=Upper Saddle River (NJ) | publisher=Pearson Education | year=2004 | id=ISBN 0-8053-5957-5}}</ref>
 
  
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.<ref name="Silverthorn2004" /> Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins.<!--
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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 2006).   
   —><ref name="AMH2006">{{cite book | editor=Rossi S, editor | title=[[Australian Medicines Handbook]] | year=2006 | location=Adelaide | publisher=Australian Medicines Handbook | id=ISBN 0-9757919-2-3}}</ref>
 
  
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.
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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.
  
 
==Developments from penicillin==
 
==Developments from penicillin==
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  —><ref name="Fleming1929">{{cite journal | author=Fleming A. | title=On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of ''B. influenzæ''. | journal=Br J Exp Pathol | year=1929 | volume=10 | issue=31 | pages=226–36}}</ref>
 +
 +
—><ref>{{cite news | author=Saxon, W. | url=http://www.wellesley.edu/Chemistry/Chem101/antibiotics/obit-a-miller.html | title=Anne Miller, 90, first patient who was saved by penicillin | publisher=The New York Times | date=[[1999-06-09]]}}</ref><!--
 +
  —><ref>{{cite web | author=Krauss K, editor | title=Yale-New Haven Hospital Annual Report | url=http://www.ynhh.org/general/annreport/ynhh99ar.pdf | format=PDF | year=1999 | publisher=Yale-New Haven Hospital | location=New Haven}}</ref>
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 +
<!--
 +
  —><ref name="Silverthorn2004">{{cite book | author=Silverthorn, DU. | title=Human physiology: an integrated approach. | edithion=3rd ed. | location=Upper Saddle River (NJ) | publisher=Pearson Education | year=2004 | id=ISBN 0-8053-5957-5}}</ref>
 +
 +
<!--
 +
  —><ref name="AMH2006">{{cite book | editor=Rossi S, editor | title=[[Australian Medicines Handbook]] | year=2006 | location=Adelaide | publisher=Australian Medicines Handbook | id=ISBN 0-9757919-2-3}}</ref>
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==External links==
 
==External links==

Revision as of 14:59, 16 December 2006

Penicillin structure
Penicillin

Penicillin (sometimes abbreviated PCN) refers to a group of β-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 of fungi, such as the mold Penicillium chrysogenum. All penicillins possess the basic Penam Skeleton, which has the molecular formula R-C9H11N2O4S, where R is a variable side chain.

It is estimated that penicillin has saved at least 200 million lives since its first use as a medicine in 1942.


History

Penicillium fungus, ancient remedy

The serendipitous discovery of penicillin is usually attributed to Scottish scientist Alexander Fleming, though others had earlier noted the antibacterial effects of Penicillium. (Penicillium is a member of the deuteromycetes, fungi with no known sexual state. As it grows, it gives off the liquid referred to as penicillin.) Many ancient cultures, including the ancient Greeks and ancient Chinese, already used molds and other plants to treat infection. This worked because some molds produce antibiotic substances. However, they couldn't distinguish or distill the active component in the molds. There also are many old remedies where mould is involved. In Serbia and in Greece, moldy bread was a traditional treatment for wounds and infections.

Sir John Scott Burdon-Sanderson, who started out at St. Mary's Hospital 1852-1858 and as lecturer there 1854-1862, observed in 1870 that culture fluid covered with mold would produce no bacteria. In 1871, Joseph Lister, an English surgeon and the father of modern antisepsis, described that urine samples contaminated with moud did not allow the growth of bacteria and he also described the antibacterial action on human tissue on what he called Penicillium Glaucum. A nurse at Kings College Hospital, whose wounds did not respond to any antiseptic, was then given another substance which cured her, and Lister's registrar informed her that it was called Penicillium. Louis Pasteur and Jules Francois Joubert in 1877 had observed that cultures of the anthrax bacilli, when contaminated with molds, became inhibited. Some references say that Pasteur identified the strain as Penicillium notatum.

In 1928, 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 mold on a Staphylococcus plate culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a Penicillium mold, now known to be Penicillium chrysogenum (also known as P. notatum). Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mold. Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. (Gram-positive (as opposed to gram-negative) refers to the characteristic blue-violet color reaction of certain types of bacteria in what is called the Gram-staining procedure. A major feature of gram-positive bacteria is the high percentage of peptidoglycan (sugar + amino acid molecule) in the cell wall.) Fleming expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, but particularly noted its laboratory value in the isolation of "Bacillus influenzae" (now Haemophilus influenzae) (Fleming 1929).

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 find 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. (Bactericidal refers to inhibition of the growth or activity of bacteria, thus the prevention of infection.) 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 March 14, 1942 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin (Saxon 1999, Krauss 1999).[1]

—>[2][3]

[4]

[5]


External links


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  1. Fleming A. (1929). On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ.. Br J Exp Pathol 10 (31): 226–36.
  2. Saxon, W.. "Anne Miller, 90, first patient who was saved by penicillin", The New York Times, 1999-06-09.
  3. Krauss K, editor (1999). Yale-New Haven Hospital Annual Report (PDF). Yale-New Haven Hospital.
  4. Silverthorn, DU. (2004). Human physiology: an integrated approach.. Upper Saddle River (NJ): Pearson Education. ISBN 0-8053-5957-5. 
  5. (2006) in Rossi S, editor: Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3.