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Penicillin core structure.
^ Penicillin core structure Discovery and history .

^ Penicillin Core Chemical Structure .
  • MOA of Penicillin Antibiotics: Mode of Action of Amoxicillin & other Beta-lactam Antimiocrobics 15 January 2010 5:15 UTC bacteriology.suite101.com [Source type: Academic]

"R" is variable group.
.Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi.^ PC Pen VK Penicillin V is an antibiotic in the penicillin group of drugs.

^ Dicloxacillin Dicloxacillin is an antibiotic in the penicillin group of drugs.

^ Oxacillin Oxacillin is an antibiotic in the penicillin group of drugs.

[1] .Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections.^ Penicillin : First antibiotic isolated and used in treatment of bacterial diseases and infections.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

^ Ampicillin Ampicillin is an antibiotic in the penicillin group of drugs.

^ Penicillin was the first naturally-produced antibiotic .
  • Dr. Fleming, Penicillin and the Penicillium Mold: Penicillin Discovery and Killing of Gram Positive Cocci, Gonococci 15 January 2010 5:15 UTC human-infections.suite101.com [Source type: Academic]

.Penicillins are still widely used today, though many types of bacteria are now resistant.^ Most staphylococci now are resistant to penicillin.
  • penicillin V (Veetids, Pen-Vee-K) Drug Information on MedicineNet.com 15 January 2010 5:15 UTC www.medicinenet.com [Source type: FILTERED WITH BAYES]

^ A different type of penicillin is used on animals .
  • WikiAnswers - What is penicillin for 15 January 2010 5:15 UTC wiki.answers.com [Source type: General]

^ Penicillinase-resistant penicillins used for penicillinase (beta lactamase) producing bacteria .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

.All penicillins are Beta-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.^ It is resistance to antibiotics that will cause a recurring infection.” .
  • Penicillin overuse puts Fleming's legacy at risk - Times Online 15 January 2010 5:15 UTC www.timesonline.co.uk [Source type: News]

^ If an infection develops, other antibiotics can be used for bacteria that are resistant to penicillin.
  • The Infant and Young child with Sickle Cell Anemia 15 January 2010 5:15 UTC www.doh.wa.gov [Source type: FILTERED WITH BAYES]

^ Mechanism of action of the beta lactam antibiotics (penicillins and cephalosporins) .
  • Beta lactams antibiotics (penicillins and cephalosporins) mechanism of action: videos and animations | Pharmamotion 15 January 2010 5:15 UTC pharmamotion.com.ar [Source type: Academic]

.The term "penicillin" can also refer to the mixture of substances that are naturally, and organically, produced.^ Penicillin was the first naturally-produced antibiotic .
  • Dr. Fleming, Penicillin and the Penicillium Mold: Penicillin Discovery and Killing of Gram Positive Cocci, Gonococci 15 January 2010 5:15 UTC human-infections.suite101.com [Source type: Academic]

^ The mould produced a substance, named penicillin by Fleming, which inhibited bacterial growth and was later found to be effective against a wide range of harmful bacteria.
  • Fleming - Penicillin 15 January 2010 5:15 UTC www.rsc.org [Source type: Academic]

^ The term “penicillin” is often used generically to refer to one of the narrow-spectrum penicillins, particularly benzylpenicillin.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

[2]

Contents

Structure

Penicillin core structure, in 3D. Purple is variable group.
.The term "penam" is used to describe the core skeleton of a member of a penicillin antibiotic.^ In 1957 Sheehan synthesized penicillin and first used the term antibiotic .
  • Penicillin: Medicine's Wartime Wonder Drug and Its Production at Peoria, Illinois 15 January 2010 5:15 UTC www.lib.niu.edu [Source type: FILTERED WITH BAYES]

^ Penicillin” is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Conclusions: Penicillin skin testing continues to be safe and changes subsequent frequency of antibiotic use and type of antibiotic prescribed.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]
  • Penicillin - .net fusion 15 January 2010 5:15 UTC dotnetarch.com [Source type: FILTERED WITH BAYES]

.This skeleton has the molecular formula R-C9H11N2O4S, where R is a variable side chain.^ Penicillin” is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ The name “penicillin” can also be used in reference to a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ The various side chains may add other characteristics that distinguish one beta-lactam antibiotic from another.

.Normal penicillin has a molecular weight of 313[3] to 334[4][5] g/mol (latter for penicillin G).^ Mechanisms: Penicillin is a low molecular weight substance which needs to combine with protein to become immunogenic.
  • Drug Allergy, Asthma and Allergy 15 January 2010 5:15 UTC www.allergysa.org [Source type: Academic]
  • How long does it take for penicillin to get out of your system? - Yahoo!7 Answers 15 January 2010 5:15 UTC au.answers.yahoo.com [Source type: FILTERED WITH BAYES]

^ Like many pharmacologic agents, penicillin is simple in structure and of low molecular weight.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

^ Penicillin-cephalosporin cross-reactivity Penicillins and cephalosporins have similar beta-lactam ring structures, are of low molecular weight, and are highly substituted on their side chains.
  • Skyscape Content: The latest word on penicillin allergy 15 January 2010 5:15 UTC mediwire.skyscape.com [Source type: Academic]

.Penicillin types with additional molecular groups attached may have a molar mass around 500 g/mol.^ Penicillin” is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Penicillin is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain.

^ Penicillin is the drug of choice for several types of infections and recent literature suggests it may be better than other agents (particularly vancomycin) in several infections.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

For example, cloxacillin has a molar mass of 476 g/mol and dicloxacillin has a molar mass of 492 g/mol.[6]

Biosynthesis

Penicillin biosynthesis
.Overall, there are a total of three main and important steps to the biosynthesis of penicillin G (benzylpenicillin).^ Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.
  • Penicillin V Potassium - Erewhon Natural Foods 15 January 2010 5:15 UTC www.erewhonmarket.com [Source type: Academic]

^ Chain, Ernst : One of the main scientists who worked with Florey in the research with penicillin, and one of the three scientist to share the Nobel Prize, in 1945, for their work on penicillin, in physiology and medicine.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

^ The Aspergillus nidulans npeA locus consists of three contiguous genes required for penicillin biosynthesis.
  • Production of Penicillin by Fungi Growing on Food Products: Identification of a Complete Penicillin Gene Cluster in Penicillium griseofulvum and a Truncated Cluster in Penicillium verrucosum -- Laich et al. 68 (3): 1211 -- Applied and Environmental Microbiology 15 January 2010 5:15 UTC aem.asm.org [Source type: Academic]

.The first step in the biosynthesis of penicillin G is the condensation of three amino acids L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide.^ Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.
  • Penicillin G Benzathine and Penicillin G Procaine - MOM's-Rockville 15 January 2010 5:15 UTC www.myorganicmarket.com [Source type: Academic]

^ The lactam structure can also be viewed as the covalent bonding of pieces of two amino acids - cysteine (blue) and valine (red).
  • Drugs - Pencillin 15 January 2010 5:15 UTC www.elmhurst.edu [Source type: Academic]
  • Penicillin - ChemWiki 15 January 2010 5:15 UTC chemwiki.ucdavis.edu [Source type: FILTERED WITH BAYES]

^ If D,L-6-(α-amino-furfurylacetamido)-penicillanic acid is used as the starting material, the penicillins of Example 1 and 2 are obtained as diastereomer mixtures which can be separated into the α-D-form and α-L-form by, for example, preparative high pressure liquid chromatography.

[7][8][9]Before condensing into a tripeptide, the amino acid L-valine will undergo epimerization and become D-valine.[10][11] .After the condensation, the tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine which is also known as ACV. While this reaction occurs, we need to add in a required catalytic enzyme ACVS which is also known as δ-(L-α-aminoadipyl)-L-cysteine-D-valine synthetase.^ Aminoadipyl-cysteinyl-valine synthetases in ß-lactam producing organisms.
  • Production of Penicillin by Fungi Growing on Food Products: Identification of a Complete Penicillin Gene Cluster in Penicillium griseofulvum and a Truncated Cluster in Penicillium verrucosum -- Laich et al. 68 (3): 1211 -- Applied and Environmental Microbiology 15 January 2010 5:15 UTC aem.asm.org [Source type: Academic]

^ The pool of penicillin biosynthetic precursors 2-aminoadipate, cysteine and valine is sequestered in vacuoles, along with the vacuolar membrane-associated ACV synthase.
  • MetaCyc penicillin K biosynthesis 15 January 2010 5:15 UTC ecocyc.org [Source type: Academic]

^ E gene codes for the enzyme penicillin N expandase {also known as deacetoxycephalosporin C synthetase (DAOCS)} .

.This catalytic enzyme ACVs is required for the activation of the three amino acids before condensation and the epimerization of transforming L-valine to D-valine.^ These enzymes are organized in domains, each activating one amino acid.
  • Production of Penicillin by Fungi Growing on Food Products: Identification of a Complete Penicillin Gene Cluster in Penicillium griseofulvum and a Truncated Cluster in Penicillium verrucosum -- Laich et al. 68 (3): 1211 -- Applied and Environmental Microbiology 15 January 2010 5:15 UTC aem.asm.org [Source type: Academic]

^ The lactam structure can also be viewed as the covalent bonding of pieces of two amino acids - cysteine (blue) and valine (red).
  • Drugs - Pencillin 15 January 2010 5:15 UTC www.elmhurst.edu [Source type: Academic]
  • Penicillin - ChemWiki 15 January 2010 5:15 UTC chemwiki.ucdavis.edu [Source type: FILTERED WITH BAYES]

^ A bulky group attached to the amino acid side chain provides steric hindrance which interfers with the enzyme attachment which would deactivate the pencillins i.e.
  • Drugs - Pencillin 15 January 2010 5:15 UTC www.elmhurst.edu [Source type: Academic]
  • Penicillin - ChemWiki 15 January 2010 5:15 UTC chemwiki.ucdavis.edu [Source type: FILTERED WITH BAYES]

.The second step in the biosynthesis of penicillin G is to use an enzyme to change ACV into isopenicillin N. The enzyme is isopenicillin N synthase with the gene pcbC enclosed.^ C gene, which encodes the isopenicillin N synthase, as also occurs in P .

^ Conclusions: Penicillin skin testing continues to be safe and changes subsequent frequency of antibiotic use and type of antibiotic prescribed.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]
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^ Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.
  • Penicillin G Benzathine and Penicillin G Procaine - MOM's-Rockville 15 January 2010 5:15 UTC www.myorganicmarket.com [Source type: Academic]

.The tripeptide on the ACV will then undergo oxidation which then allows a ring closure so that a bicyclic ring is formed.^ However, after degradation, penicillin forms a stable penicilloate ring, with preservation of the thiazolidine ring, whereas cephalosporins undergo rapid fragmentation of the ß-lactam and dihydrothiazine rings.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ After degradation, penicillin forms a stable ring, whereas cephalosporins undergo rapid fragmentation of their rings.
  • Cephalosporins can be prescribed safely for penicillin-allergic patients — The Journal of Family Practice 15 January 2010 5:15 UTC www.jfponline.com [Source type: Academic]

^ After degradation, penicillin forms a stable penicilloate ring with preservation of the thiazolidine ring, whereas cephalosporins undergo rapid fragmentation of the beta-lactam and dihydrothiazine rings.
  • Skyscape Content: The latest word on penicillin allergy 15 January 2010 5:15 UTC mediwire.skyscape.com [Source type: Academic]

[7][8] .Isopenicillin N is a very weak intermediate because it does not show much antibiotic activity.^ The second reaction involves oxidative ring closure catalyzed by isopenicillin-N synthase leading to the formation of isopenicillin N. Isopenicillin N has weak antibiotic activity and is the first bioactive intermediate in the pathway.
  • MetaCyc penicillin K biosynthesis 15 January 2010 5:15 UTC ecocyc.org [Source type: Academic]

^ Study of antibiotic ( penicillin ) pharmacokinetics showed increase of its biological activity and prolongation of its presence in the blood in therapeutic concentrations for 24-48 hours .

^ This was a very important discovery because it opened up the option of creating a new antibiotic.
  • The Evolution of Resistance to Penicillin 15 January 2010 5:15 UTC webpub.allegheny.edu [Source type: FILTERED WITH BAYES]

[10] .The Last step in the biosynthesis of penicillin G is the exchange the side chain group so that isopenicillin N will become penicillin G. Through the catalytic coenzyme isopenicillin N acyltransferase (IAT), the alpha-aminoadipyl side chain of isopenicillin N is removed and exchanged for a phenylacetyl side chain.^ In the third step, the hydrophilic L-α-aminoadipate side chain is exchanged for a a hydrophobic acyl group, catalyzed by isopenicillin-N N -acyltransferase.
  • MetaCyc penicillin K biosynthesis 15 January 2010 5:15 UTC ecocyc.org [Source type: Academic]

^ Penicillin” is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Penicillin is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C 9 H 11 N 2 O 4 S, where R is a variable side chain.

.This reaction is encoded by the gene penDE which is unique in the process of obtaining penicillins.^ Tp47 also exhibits a penicillin binding reaction, in the process of which the enzyme is covalently modified in the active site .

^ This is because the penicillin attacks a process that is unique to bacteria and not found in higher organisms.
  • RCSB Protein Data Bank : Molecule of the Month - Penicillin-binding Proteins 15 January 2010 5:15 UTC www.rcsb.org [Source type: Academic]

^ The processes of preparation are characterized by the reaction of neutralized polylysine hydrochloride with penicillin in a non-aqueous polar solvent.
  • Compositions and methods therewith for penicillin hypersensitivity detection - Patent 3979508 15 January 2010 5:15 UTC www.freepatentsonline.com [Source type: Academic]

[7]

History

Discovery

.The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in 1928.[12] He showed that, if Penicillium notatum was grown in the appropriate substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin.^ The first modern antibiotic, penicillin , was an accidental discovery of the Scottish bacteriologist Alexander Fleming, in 1928.
  • Discovery of Penicillin - Kosmix : Reference, Videos, Images, News, Shopping and more... 15 January 2010 5:15 UTC science.kosmix.com [Source type: General]

^ The discovery of penicillin is usually attributed to Scottish scientist Sir Alexander Fleming in 1928 and the development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey.

^ Penicillin is a fungal-derived antibiotic discovered by Alexander Fleming in 1928.
  • Tag: Penicillin - Explore content tagged Penicillin on eHow.com 15 January 2010 5:15 UTC www.ehow.com [Source type: General]

.This serendipitous observation began the modern era of antibiotic discovery.^ The story of the world's first antibiotic, a discovery that languished for a decadeuntil a team of Oxford scientists made it into the wonder drug that changed the modern world.
  • Powell's Books - The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle (John MacRae Books) by Eric Lax 15 January 2010 5:15 UTC www.powells.com [Source type: General]

^ The first modern antibiotic, penicillin , was an accidental discovery of the Scottish bacteriologist Alexander Fleming, in 1928.
  • Discovery of Penicillin - Kosmix : Reference, Videos, Images, News, Shopping and more... 15 January 2010 5:15 UTC science.kosmix.com [Source type: General]

^ How rare was this serendipitous event and was the discovery of penicillin really the result of an unexpected chance observation by a single researcher?

.The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley.^ The discovery of penicillin is usually attributed to Scottish scientist Sir Alexander Fleming in 1928 and the development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey.

^ Howard Florey  shared the Nobel Prize for Medicine for extracting penicillin.
  • The My Hero Project - Sir Alexander Fleming 15 January 2010 5:15 UTC www.myhero.com [Source type: FILTERED WITH BAYES]

^ The other scientists were Howard Florey and Ernst Chain.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

.However, several others reported the bacteriostatic effects of Penicillium earlier than Fleming.^ However, several others had earlier noted the antibacterial effects of Penicillium such as Ernest Duchesne, who documented it in his 1897 paper; however it was not accepted by the Institut Pasteur because of his young age.

^ The serendipitous discovery of penicillin is usually attributed to Scottish scientist Alexander Fleming in 1928, though others had earlier noted the antibacterial effects of Penicillium.
  • Benzylpenicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ However, several others had noted earlier the bacteriostatic effects of Penicillium : The first published reference appears to have been in 1875, when it was reported to the Royal Society in London by John Tyndall .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

.The use of bread with a blue mould (presumably penicillium) as a means of treating suppurating wounds was a staple of folk medicine in Europe since the Middle Ages.^ Today this is called the 'Penicillium chrysogenum' and the term Penicillin was used to refer to the broth culture of the mould.
  • What Year Was The First "Penicillin Invented"? - Blurtit 15 January 2010 5:15 UTC www.blurtit.com [Source type: General]

^ Pyritinol has been used in Europe since 1961 for various cognitive conditions such as dementia, head injury, stroke aftermath, coma, and cerebral circulatory disorders.
  • mail order antibiotics, penicillin, tetracycline, doxycycline, Roxithromycine, Cipro,smart drugs, antidepressants, Viagra 15 January 2010 5:15 UTC www.antiaging-systems.net [Source type: Academic]

^ These events gave great urgency to development of a process which would produce medicinal penicillin in sufficient quantities to treat ever increasing numbers of war wounds.

.The first published reference appears in the publication of the Royal Society in 1875, by John Tyndall.^ The first published reference to the bacteriostatic effect of Penicillium appears to be by John Tyndall [1] .

^ However, several others had noted earlier the bacteriostatic effects of Penicillium : The first published reference appears to have been in 1875, when it was reported to the Royal Society in London by John Tyndall .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ In 1875 John Tyndall reported to the Royal Society in London that a species of Penicillium had caused some of his bacteria to burst.
  • SHiPS Resource Center || Penicillin & Chance 15 January 2010 5:15 UTC www1.umn.edu [Source type: FILTERED WITH BAYES]

[13] .Ernest Duchesne documented it in an 1897 paper, which was not accepted by the Institut Pasteur because of his youth.^ Ernest Duchesne documented it in his 1897 paper; however it was not accepted by the Institut Pasteur because of his young age.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Most dramatically, Ernest Duchesne had completed a doctoral dissertation in 1897 on the evolutionary competition among microorganisms, focusing on the interaction between E. coli and Penicillium glaucum .
  • SHiPS Resource Center || Penicillin & Chance 15 January 2010 5:15 UTC www1.umn.edu [Source type: FILTERED WITH BAYES]

^ In 1897, Ernest Duchesne had completed his Ph.D. on on the evolutionary competition among microorganisms.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

.In March 2000, doctors at the San Juan de Dios Hospital in San José, Costa Rica published the manuscripts of the Costa Rican scientist and medical doctor Clodomiro (Clorito) Picado Twight (1887–1944).^ In March 2000, doctors at the San Juan de Dios Hospital in San Jose ( Costa Rica ) published manuscripts belonging to the Costa Rican scientist and medical doctor Clodomiro (Clorito) Picado Twight (1887–1944).
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Furthermore, in March 2000, doctors of the San Juan de Dios Hospital in San Jose (Costa Rica) published manuscripts belonging to the Costa Rican scientist and medical doctor Clodomiro (Clorito) Picado Twight (1887-1944).

^ Widow Died after Doctors Ignored Penicillin Warning; June Cutmore: Allergic Reaction...died after hospital doctors gave her penicillin even though her medical notes and drug...Basildon.
  • Penicillin: Free Encyclopedia Articles at Questia.com Online Library 15 January 2010 5:15 UTC www.questia.com [Source type: Academic]

.They reported Picado's observations on the inhibitory actions of fungi of the genus Penicillium between 1915 and 1927. Picado reported his discovery to the Paris Academy of Sciences, yet did not patent it, even though his investigations started years before Fleming's.^ The manuscripts explained Picado's experiences between 1915 and 1927 about the inhibitory actions of the fungi of genera Penic.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Clorito Picado had reported his discovery to the Paris Academy of Sciences in Paris, yet did not patent it, even though his investigation had started years before Fleming's.

^ Clorito Picado had reported his discovery to the Paris Academy of Sciences, yet did not patent it, even though his investigation had started years before Fleming's.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

Fleming recounted that the date of his breakthrough was on the morning of Friday, September 28, 1928.[14] It was a fortuitous accident: in his laboratory in the basement of St. Mary's Hospital in London (now part of Imperial College), Fleming noticed a petri dish containing Staphylococcus plate culture he had mistakenly left open, which was contaminated by blue-green mould, which had formed a visible growth. .There was a halo of inhibited bacterial growth around the mould.^ Returning from vacation in the summer of 1928, he noticed that mold was partly covering one of the agar plates in which he had been growing bacteria, and that the mold inhibited bacterial cell growth.
  • Teachers' Domain: The Discovery of Penicillin 15 January 2010 5:15 UTC www.teachersdomain.org [Source type: FILTERED WITH BAYES]

^ Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold staphylococcus plate culture.

^ In 1928 Alexander Fleming discovered accidentally that a mould (Penicillium notatum) contaminating left over cultures of bacteria was actually inhibiting bacterial growth.
  • Penicillium and Penicillin - Naked Scientists Discussion Forum 15 January 2010 5:15 UTC www.thenakedscientists.com [Source type: FILTERED WITH BAYES]

.Fleming concluded that the mould was releasing a substance that was repressing the growth and lysing the bacteria.^ Fleming concluded that the mould was releasing a substance that was inhibiting bacterial growth and lysing the bacteria.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria.
  • Penicillin 15 January 2010 5:15 UTC itech.dickinson.edu [Source type: FILTERED WITH BAYES]
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^ As early as 1922, he had discovered an enzyme present in biological substances as varied as egg whites, tears and mucus that causes bacteria to lyse, or burst.

.He grew a pure culture and discovered that it was a Penicillium mould, now known to be Penicillium notatum.^ He grew a pure culture of the mould and discovered that it was a Penicillium mould, now known to be Penicillium chrysogenum.
  • Benzylpenicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ He grew a pure culture of the mold and discovered that it was a Penicillium mold, now known to be Penicillium notatum .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ He grew a pure culture of the mould and discovered that it was a Penicillium mould, now known to be Penicillium notartum .

.Charles Thom, an American specialist working at the U.S. Department of Agriculture, was the acknowledged expert, and Fleming referred the matter to him.^ Charles Thom , an American specialist working at the U.S. Department of Agriculture, was the acknowledged expert, and Fleming referred the matter to him.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ The National Academy of Sciences was consulted and sent them to Charles Thom, noted Penicillium expert (and coauthor of the monograph of Penicillium with Ken Raper).
  • Penicillium chrysogenum (aka P. notatum), the natural source for the wonder drug penicillin, the first antibiotic. Tom Volk's Fungus of the Month for November 2003 15 January 2010 5:15 UTC botit.botany.wisc.edu [Source type: FILTERED WITH BAYES]

^ The actor (i.e., Fleming) caused events: contributed his findings to the medical world by publishing a report to a journal; a team of chemists and mould specialists took over the work with the mould.
  • Science as Narrative 15 January 2010 5:15 UTC www.pantaneto.co.uk [Source type: FILTERED WITH BAYES]

.Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould.^ Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mold.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould.
  • Benzylpenicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Today this is called the 'Penicillium chrysogenum' and the term Penicillin was used to refer to the broth culture of the mould.
  • What Year Was The First "Penicillin Invented"? - Blurtit 15 January 2010 5:15 UTC www.blurtit.com [Source type: General]

.Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi.^ Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria.
  • DrugBank: Search Results 15 January 2010 5:15 UTC www.drugbank.ca [Source type: Academic]
  • DrugBank: Search Results 15 January 2010 5:15 UTC www.drugbank.ca [Source type: Academic]

^ Penicillin is most effective at eradicating growing gram positive bacteria.

^ Flucloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria.
  • DrugBank: Search Results 15 January 2010 5:15 UTC www.drugbank.ca [Source type: Academic]
  • DrugBank: Search Results 15 January 2010 5:15 UTC www.drugbank.ca [Source type: Academic]

.He expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, and noted its laboratory value in the isolation of "Bacillus influenzae" (now Haemophilus influenzae).^ He expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, but, in particular, noted its laboratory value in the isolation of " Bacillus influenzae " (now Haemophilus influenzae ).
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ He 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).
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ He 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 ).
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

[15] After further experiments, Fleming was convinced that penicillin could not last long enough in the human body to kill pathogenic bacteria, and stopped studying it after 1931. He restarted clinical trials in 1934, and continued to try to get someone to purify it until 1940.[16]

Medical application

.In 1930 Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use penicillin to treat sycosis barbae–eruptions in beard follicles, but was unsuccessful, probably because the drug did not penetrate the skin deeply enough.^ His first effort at using penicillin was in treating patients with a skin infection called sycosis barbae .
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ Conclusions: Penicillin skin testing continues to be safe and changes subsequent frequency of antibiotic use and type of antibiotic prescribed.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]
  • Penicillin - .net fusion 15 January 2010 5:15 UTC dotnetarch.com [Source type: FILTERED WITH BAYES]

^ "Later," Hobby wrote, "the techniques we used seemed very primitive, but they provided enough concentrated and partially purified penicillin to convince us of the efficacy of the drug and enough even to help save a few patients' lives."
  • The Drug That Changed the World 15 January 2010 5:15 UTC cumc.columbia.edu [Source type: FILTERED WITH BAYES]

.Moving on to ophthalmia neonatorum – a gonococcal infection in infants – he achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, failing to cure a fifth.^ He cured four patients (one adult, three babies) of eye infections, although a fifth patient was not so lucky.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ When was penicillin first used successfully on a patient?
  • penicillin – FREE penicillin information | Encyclopedia.com: Find penicillin research 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]
  • penicillin Facts, information, pictures | Encyclopedia.com articles about penicillin 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]

^ He cured four patients, one adult the others babies, of eye infections although a fifth patient was not so lucky.

[17]
.In 1939, Australian scientist Howard Florey (later Baron 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.^ In 1939, Australian scientist Howard Florey (later Baron 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.

^ Howard Florey looked with Margaret Jennings at the impact of penicillin on animals.
  • Howard Florey - Maker of the Miracle Mould 15 January 2010 5:15 UTC www.abc.net.au [Source type: FILTERED WITH BAYES]

^ Florey, Howard : In1938, directed his efforts to doing research with penicillin, at Oxford.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

.Their attempts to treat humans failed due to insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert Alexander), but they proved it harmless and effective on mice.^ When was penicillin first used successfully on a patient?
  • penicillin Facts, information, pictures | Encyclopedia.com articles about penicillin 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]

^ Their attempts to treat humans failed due to insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert Alexander ), but they proved it harmless and effective on mice.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ The patient was treated with penicillin and improved clinically .

[18]
.Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford, England.^ Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ I took some penicillin and it made me feel worse.
  • Penicillin discussions (experiences, side effects, dosages, etc...) 15 January 2010 5:15 UTC www.drugtalk.com [Source type: General]

^ What I did was take some penicillin from an old prescription (2 months) and took that ...
  • Penicillin discussions (experiences, side effects, dosages, etc...) 15 January 2010 5:15 UTC www.drugtalk.com [Source type: General]

.These trials continue to be cited by some sources as the first cures using penicillin, though the Paine trials took place earlier.^ Penicillin was the first antibiotic to be used to treat or cure disease.
  • Teachers' Domain: The Discovery of Penicillin 15 January 2010 5:15 UTC www.teachersdomain.org [Source type: FILTERED WITH BAYES]
  • Teachers' Domain: Producing Penicillin 15 January 2010 5:15 UTC www.teachersdomain.org [Source type: FILTERED WITH BAYES]

^ Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Conclusions: Penicillin skin testing continues to be safe and changes subsequent frequency of antibiotic use and type of antibiotic prescribed.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]
  • Penicillin - .net fusion 15 January 2010 5:15 UTC dotnetarch.com [Source type: FILTERED WITH BAYES]

[17] .On March 14, 1942, John Bumstead and Orvan Hess saved a dying patient's life using penicillin.^ When was penicillin first used successfully on a patient?
  • penicillin Facts, information, pictures | Encyclopedia.com articles about penicillin 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]

^ On 1942-03-14 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.
  • Benzylpenicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ On March 14 1942 , John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

[19][20]

Mass production

.The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s.^ The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s, enabling synthetic production.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Model of Structure of Penicillin, by Dorothy Hodgkin et al., Museum of the History of Science, Oxford Wikipedia, the free encyclopedia © 2001-2006 Wikipedia contributors ( Disclaimer ) This article is licensed under the GNU Free Documentation License .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

.Penicillin has since become the most widely used antibiotic to date, and is still used for many Gram-positive bacterial infections.^ If an infection develops, other antibiotics can be used for bacteria that are resistant to penicillin.
  • The Infant and Young child with Sickle Cell Anemia 15 January 2010 5:15 UTC www.doh.wa.gov [Source type: FILTERED WITH BAYES]

^ Penicillin is most effective at eradicating growing gram positive bacteria.

^ This medication is used to treat a wide variety of bacterial infections.
  • Penicillin G Sodium Inj Drug information on Uses, Side Effects, Interactions, and User Reviews on RxList 15 January 2010 5:15 UTC fdb.rxlist.com [Source type: General]

.A team of Oxford research scientists led by Australian Howard Florey and including Ernst Boris Chain and Norman Heatley devised a method of mass-producing the drug.^ We now turn to Oxford, and the scientists Howard Florey, Ernst Chain, and Norman Heatley.
  • Jack's "Bugs in the News" - What the Heck is Penicillin? 15 January 2010 5:15 UTC people.ku.edu [Source type: FILTERED WITH BAYES]

^ The challenge of mass-producing the drug had been daunting.
  • Penicillin: Medicine's Wartime Wonder Drug and Its Production at Peoria, Illinois 15 January 2010 5:15 UTC www.lib.niu.edu [Source type: FILTERED WITH BAYES]
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Ernst B. Chain, Leslie Falk, Norman G. Heatley and twenty other scientists and technicians.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

.Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for their work.^ Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Howard Florey  shared the Nobel Prize for Medicine for extracting penicillin.
  • The My Hero Project - Sir Alexander Fleming 15 January 2010 5:15 UTC www.myhero.com [Source type: FILTERED WITH BAYES]

^ Baron Florey and Ernst Boris Chain the two men that he shared the Nobel Prize with.

.After World War II, Australia was the first country to make the drug available for civilian use.^ In fact, Australia was the first country that made the drug available for civilian use.
  • Howard Florey - Maker of the Miracle Mould 15 January 2010 5:15 UTC www.abc.net.au [Source type: FILTERED WITH BAYES]

^ Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work, and, after WWII, Australia was the first country to make the drug available for civilian use.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ 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.
  • penicillin Facts, information, pictures | Encyclopedia.com articles about penicillin 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]
  • Penicillin: Free Encyclopedia Articles at Questia.com Online Library 15 January 2010 5:15 UTC www.questia.com [Source type: Academic]

.Chemist John C. Sheehan at MIT completed the first total synthesis of penicillin and some of its analogs in the early 1950s, but his methods were not efficient for mass production.^ Chemist John Sheehan at MIT completed the first total synthesis of penicillin and some of its analogs in the early 1950s, but his methods were not efficient for mass production.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ On 1942-03-14 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s, enabling synthetic production.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

.The challenge of mass-producing this drug was daunting.^ The challenge of mass-producing the drug had been daunting.
  • Penicillin: Medicine's Wartime Wonder Drug and Its Production at Peoria, Illinois 15 January 2010 5:15 UTC www.lib.niu.edu [Source type: FILTERED WITH BAYES]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ But Pfizer was determined to succeed in the quest to mass-produce this lifesaving new drug.
  • History of WWII Medicine 15 January 2010 5:15 UTC home.att.net [Source type: FILTERED WITH BAYES]

^ We learned how to mass produce these substances in labs, and drug therapy was status quo for treating microbial diseases.

On March 14, 1942, the first patient was treated for streptococcal septicemia with U.S.-made penicillin produced by Merck & Co.[21] .Half of the total supply produced at the time was used on that one patient.^ Of the total patient group, 53.13% were positive to one or more minor antigenic determinants, while 37.5% (12/32) were positive to one or more major antigenic determinants .

.By June 1942, there was just enough U.S. penicillin available to treat ten patients.^ By June 1942 there was just enough available to treat ten patients.
  • Penicillin: Medicine's Wartime Wonder Drug and Its Production at Peoria, Illinois 15 January 2010 5:15 UTC www.lib.niu.edu [Source type: FILTERED WITH BAYES]

^ By June 1942 there was just enough U.S. penicillin available to treat ten patients.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ The patient was treated with penicillin and improved clinically .

[22] .A moldy cantaloupe in a Peoria, Illinois market in 1943 was found to contain the best and highest-quality penicillin after a worldwide search.^ A mouldy cantaloupe in a Peoria market in 1941 was found to contain the best and highest quality penicillin after a world-wide search.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ A moldy cantaloupe in a Peoria, Illinois market in 1943 was found to contain the best and highest-quality penicillin after a world-wide search.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Eventually, one was found, on a moldy cantaloupe in a market in Peoria, Illinois.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

[23] .The discovery of the cantaloupe, and the results of fermentation research on corn steep liquor at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. Large-scale production resulted from the development of deep-tank fermentation by chemical engineer Margaret Hutchinson Rousseau.^ At the time of this plan, 425 million units were being produced.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ The discovery of the cantaloupe, and the results of fermentation research on corn-steep liquid at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the USA to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Thom sent them to the new Fermentation Division of the newly created Northern Regional Research Laboratory (NRRL) in Peoria, Illinois.
  • Penicillium chrysogenum (aka P. notatum), the natural source for the wonder drug penicillin, the first antibiotic. Tom Volk's Fungus of the Month for November 2003 15 January 2010 5:15 UTC botit.botany.wisc.edu [Source type: FILTERED WITH BAYES]

[24]
Penicillin was being mass-produced in 1944
.G. Raymond Rettew made a significant contribution to the American war effort by his techniques to produce commercial quantities of penicillin.^ Later, many pharmaceutical companies made significant contributions to the produc­tion of penicillin.
  • Fleming, Florey, Chain, and the «Wonder Drug» Penicillin 15 January 2010 5:15 UTC puckeypower.com [Source type: FILTERED WITH BAYES]

^ With the help of the British government, Florey and Chain used a beer-brewing technology to produce the quantities of moldy liquor needed for large-scale penicillin production.
  • Teachers' Domain: Producing Penicillin 15 January 2010 5:15 UTC www.teachersdomain.org [Source type: FILTERED WITH BAYES]

^ The penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress and will produce plenty of penicillin.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

[25] .During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives.^ During World War II , penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ 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.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ During World War I, his attention was focused on the wounded under bombardment.
  • BRITS AT THEIR BEST – British Inventions Penicillin It Was A "Miracle" Copyright 2006 David Abbott and Catherine Glass 15 January 2010 5:15 UTC www.britsattheirbest.com [Source type: FILTERED WITH BAYES]

.February 2008" style="white-space:nowrap;">[citation needed] 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.^ 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.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]

^ 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.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Florey, later working with biochemist Ernst Chain, found it difficult to make large quantities of penicillin in his lab.

.Penicillin is actively excreted and about 80% of a penicillin dose is cleared from the body within three to four hours of administration.^ Penicillins are actively secreted and about 80% of a penicillin dose is cleared within three to four hours of administration.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ About 12 hours after a dose, the penicillin is almost gone from the body.
  • The Infant and Young child with Sickle Cell Anemia 15 January 2010 5:15 UTC www.doh.wa.gov [Source type: FILTERED WITH BAYES]

^ IM dose of penicillin G excreted within lst hour .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

.Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused.^ During those times, it became common procedure to collect the urine from patients being treated so that the penicillin could be isolated and reused.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ The patient was treated with penicillin and improved clinically .

^ Penicillin allergy is the most common drug allergy.
  • Penicillin allergy 15 January 2010 5:15 UTC www.cnn.com [Source type: General]
  • Penicillin allergy 15 January 2010 5:15 UTC edition.cnn.com [Source type: General]
  • Penicillin allergy 15 January 2010 5:15 UTC www.studentnews.cnn.com [Source type: General]

[26]
.This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion.^ This was not a satisfactory solution, however, so researchers looked for a way to slow penicillin secretion.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ This was not a satisfactory solution, however; so researchers looked for a way to slow penicillin secretion.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

.They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for excretion, such that the transporter would preferentially excrete the competing molecule and the penicillin would be retained.^ 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.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ I walk down the street looking for a hotel to crash in and hope that perhaps they will be able to find me a taxi in the morning to take me to the airport.

^ This contributed to resistance because any one could go and buy penicillin, regardless if they needed it or not.
  • The Evolution of Resistance to Penicillin 15 January 2010 5:15 UTC webpub.allegheny.edu [Source type: FILTERED WITH BAYES]

.The uricosuric agent probenecid proved to be suitable.^ The uricosuric agent probenecid proved to be suitable.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
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.When probenecid and penicillin are administered together, probenecid competitively inhibits the excretion of penicillin, increasing penicillin's concentration and prolonging its activity.^ When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Study of antibiotic ( penicillin ) pharmacokinetics showed increase of its biological activity and prolongation of its presence in the blood in therapeutic concentrations for 24-48 hours .

^ Probenecid, disulfiram: May increase penicillin levels .
  • Penicillin G Benzathine - Peoples Rx - Austin's Favorite Pharmacy 15 January 2010 5:15 UTC www.peoplesrx.com [Source type: Academic]
  • Penicillin G Procaine - Nature's Oasis 15 January 2010 5:15 UTC www.shopnaturesoasis.com [Source type: Academic]
  • Penicillin G Benzathine and Penicillin G Procaine - MOM's-Rockville 15 January 2010 5:15 UTC www.myorganicmarket.com [Source type: Academic]
  • Penicillin V Potassium - Erewhon Natural Foods 15 January 2010 5:15 UTC www.erewhonmarket.com [Source type: Academic]

.Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined.^ The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
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  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Semi-synthetic products.
  • Antibiotics 15 January 2010 5:15 UTC users.rcn.com [Source type: Academic]

^ Semi-synthetic penicillins .
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
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[26] .Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins.^ Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
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^ Penicillin is the drug of choice for several types of infections and recent literature suggests it may be better than other agents (particularly vancomycin) in several infections.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

^ When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity.
  • Penicillin - Drug information from Medic8.com 15 January 2010 5:15 UTC www.medic8.com [Source type: Academic]
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

[27]

Developments from penicillin

.The narrow range of treatable diseases or spectrum of activity of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections.^ The narrow spectrum of activity of the penicillins, along with the poor activity of the orally-active phenoxymethylpenicillin, led to the search for derivatives of penicillin which could treat a wider range of infections.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

^ Spectrum of activity same as for penicillin G .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ F. Spectrum of activity of penicillin G and other narrow spectrum penicillins .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

.The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance).^ Semisynthetic penicillins produced from 6 APA .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ Penicillin G (also known as benzylpenicillin) Anti-staphylococcal penicillins (nafcillin, oxacillin, cloxacillin and dicloxacillin) Broad spectrum penicillins .
  • Allergy to penicillin and related antibiotics 15 January 2010 5:15 UTC www.uptodate.com [Source type: FILTERED WITH BAYES]

^ The term “penicillin” is often used generically to refer to one of the narrow-spectrum penicillins, particularly benzylpenicillin.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

.The first major development was ampicillin, which offered a broader spectrum of activity than either of the original penicillins.^ Spectrum of activity same as for penicillin G .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ F. Spectrum of activity of penicillin G and other narrow spectrum penicillins .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ The first major development was ampicillin, which offered a broader spectrum of activity than either of the original penicillins.

.Further development yielded beta-lactamase-resistant penicillins including flucloxacillin, dicloxacillin and meticillin.^ Cephalosporins (beta lactams, including penicillins) .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

^ Further development yielded beta-lactamase-resistant penicillins including flucloxacillin, dicloxacillin and methicillin.

^ Penicillins with beta-lactamase inhibitors .
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

.These were significant for their activity against beta-lactamase-producing bacteria species, but are ineffective against the methicillin-resistant Staphylococcus aureus strains that subsequently emerged.^ Used for penicillinase producing strains of staphylococcus .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ Strains of staphylococcus can become resistant to methicillin .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

^ Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia.
  • CDC - The Changing Epidemiology of Staphylococcus aureus? 15 January 2010 5:15 UTC www.cdc.gov [Source type: Academic]

.Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria.^ If an infection develops, other antibiotics can be used for bacteria that are resistant to penicillin.
  • The Infant and Young child with Sickle Cell Anemia 15 January 2010 5:15 UTC www.doh.wa.gov [Source type: FILTERED WITH BAYES]

^ Gram-negative range and against bacteria which form β-lactamase.

^ The line of true penicillins was the antipseudomonal penicillins, such as ticarcillin and piperacillin, useful for their activity against Gram-negative bacteria.

.However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most important, the cephalosporins, still retain it at the center of their structures.^ CLASSIFICATION: Antibiotic > beta -Lactam Antibiotics > Penicillin .

^ Cephalosporins (beta lactams, including penicillins) .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

^ Cleave beta lactam ring .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

[28]

Mechanism of action

β-Lactam antibiotics work by inhibiting the formation of .peptidoglycan cross-links in the bacterial cell wall.^ Bacterial cell walls are composed of a substance called peptidoglycan.

^ Cell wall biogenesis; peptidoglycan biosynthesis.
  • Penicillin-binding protein 1A - Clostridium perfringens 15 January 2010 5:15 UTC www.uniprot.org [Source type: Academic]
  • Penicillin-binding protein 1C - Escherichia coli (strain K12) 15 January 2010 5:15 UTC www.uniprot.org [Source type: Academic]

^ Bacterial cell wall .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

.The β-lactam moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the peptidoglycan molecules in bacteria, which weakens the cell wall of the bacterium (in other words, the antibiotic causes cytolysis or death due to osmotic pressure).^ Dicloxacillin Dicloxacillin is an antibiotic in the penicillin group of drugs.

^ Oxacillin Oxacillin is an antibiotic in the penicillin group of drugs.

^ Almost all bacteria have cell walls and they have transpeptidase enzymes that catalyze this reaction.
  • Sandwalk: How Penicillin Works to Kill Bacteria 15 January 2010 5:15 UTC sandwalk.blogspot.com [Source type: FILTERED WITH BAYES]

.In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the bacteria's existing peptidoglycan.^ In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the bacteria's existing peptidoglycan.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]
  • Penicillin Molecular Structure 15 January 2010 5:15 UTC www.worldofmolecules.com [Source type: Academic]

^ Cell wall biogenesis; peptidoglycan biosynthesis.
  • Penicillin-binding protein 1A - Clostridium perfringens 15 January 2010 5:15 UTC www.uniprot.org [Source type: Academic]

^ Bacterial cell wall .
  • List of Bacteriocidal Antimicrobials 15 January 2010 5:15 UTC compepid.tuskegee.edu [Source type: Academic]

.Gram-positive bacteria are called protoplasts when they lose their cell wall.^ Gram-positive bacteria .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

^ Gram-positive bacteria are called protoplasts when they lose their cell wall.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ When the bacteria lose their cell walls they are then called spheroplasts.
  • WikiSlice 15 January 2010 5:15 UTC dev.laptop.org [Source type: Academic]

.Gram-negative bacteria do not lose their cell wall completely and are called spheroplasts after treatment with penicillin.^ Gram-positive bacteria are called protoplasts when they lose their cell wall.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Penicillin interacts with the wall of the bacteria cell with the presence of a certain enzyme.

^ Gram-negative bacteria .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

.Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing its disruption of bacterial protein synthesis within the cell.^ Bacterial cell walls are composed of a substance called peptidoglycan.

^ Cell wall biogenesis; peptidoglycan biosynthesis.
  • Penicillin-binding protein 1C - Escherichia coli (strain K12) 15 January 2010 5:15 UTC www.uniprot.org [Source type: Academic]

^ Cell shape Cell wall biogenesis/degradation Peptidoglycan synthesis .
  • Penicillin-binding protein 1C - Escherichia coli (strain K12) 15 January 2010 5:15 UTC www.uniprot.org [Source type: Academic]

.This results in a lowered MBC for susceptible organisms.^ This results in a lowered MBC for susceptible organisms.
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

.Penicillins, like other β-lactam antibiotics, block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes.^ If an infection develops, other antibiotics can be used for bacteria that are resistant to penicillin.
  • The Infant and Young child with Sickle Cell Anemia 15 January 2010 5:15 UTC www.doh.wa.gov [Source type: FILTERED WITH BAYES]

^ CLASSIFICATION: Antibiotic > beta -Lactam Antibiotics > Penicillin .

^ Cephalosporins (beta lactams, including penicillins) .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

In contrast, they have no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of the evolution of plastid division in land plants.[29]

Variants in clinical use

.The term "penicillin" is often used in the generic sense to refer to one of the narrow-spectrum penicillins, in particular, benzylpenicillin (penicillin G).^ The term “penicillin” is often used in the generic sense to refer to one of the narrow-spectrum penicillins, in particular, benzylpenicillin .
  • Penicillin encyclopedia topics | Reference.com 15 January 2010 5:15 UTC www.reference.com [Source type: Academic]

^ Penicillins are the most widely used antibiotics for common infections as well as being the antibiotics which most often cause allergic reactions.
  • History Of Penicillin 15 January 2010 5:15 UTC www.docstoc.com [Source type: Academic]

^ Now, because we have used penicillins and cephalosporins so often (and, in many cases, when we really shouldn't have), there are many bacteria that can't be killed any more by plain penicillin or even by the "super-penicillins" and "super-cephalosporins".
  • Antibiotics, Bacteria and (not) Viruses 15 January 2010 5:15 UTC www.drreddy.com [Source type: FILTERED WITH BAYES]

Other types include:

Adverse effects

.Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include diarrhea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis).^ When was penicillin first used successfully on a patient?
  • penicillin Facts, information, pictures | Encyclopedia.com articles about penicillin 15 January 2010 5:15 UTC www.encyclopedia.com [Source type: Academic]

^ Adverse drug reactions .

^ No patient experienced adverse drug reactions.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

.Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in epileptics), and pseudomembranous colitis.^ Studies evaluating the morphological effects of epileptic seizure during pregnancy on newborns in various experimental models are valuable .

^ The most common presenting symptoms in patients with ARF were fever (100%), nausea and vomiting (95.0%), muscle pain (88.1%) and jaundice (71.3%) .

^ However, Fleming while serving with a colleague, from St. Mary's Hospital,   argued that while this was true, the antiseptics also had an adverse effect on the patient.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

[27]
.Pain and inflammation at the injection site is also common for parenterally administered benzathine benzylpenicillin, benzylpenicillin, and, to a lesser extent, procaine benzylpenicillin.^ This formulation is painful; injections that contain procaine penicillin in addition to benzathine penicillin G are less painful.
  • Treatment of Acute Streptococcal Pharyngitis and Prevention of Rheumatic Fever 15 January 2010 5:15 UTC www.americanheart.org [Source type: Academic]

^ The advantages of benzathine penicillin G must be weighed against the inconvenience to the patient and pain of injection, which causes some individuals to discontinue prophylaxis.
  • Treatment of Acute Streptococcal Pharyngitis and Prevention of Rheumatic Fever 15 January 2010 5:15 UTC www.americanheart.org [Source type: Academic]

^ Local: Pain at injection site, thrombophlebitis, sterile abscess at injection site .

.Although penicillin is still the most commonly reported allergy, less than 20% of all patients that believe that they have a penicillin allergy are truly allergic to penicillin;[30] nevertheless, penicillin is still the most common cause of severe allergic drug reactions.^ Penicillin and related antibiotics can cause an allergic reaction in some people.
  • OhioHealth - Penicillin allergy 15 January 2010 5:15 UTC www.ohiohealth.com [Source type: FILTERED WITH BAYES]
  • Penicillin allergy - Valley Health System 15 January 2010 5:15 UTC www.valleyhealth.com [Source type: FILTERED WITH BAYES]

^ Anaphylaxis is the most rare and serious possible allergic drug reaction.
  • OhioHealth - Penicillin allergy 15 January 2010 5:15 UTC www.ohiohealth.com [Source type: FILTERED WITH BAYES]
  • Penicillin allergy - Valley Health System 15 January 2010 5:15 UTC www.valleyhealth.com [Source type: FILTERED WITH BAYES]

^ Is this patient allergic to penicillin?
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]
  • Is it safe to use carbapenems in patients with a history of allergy to penicillin? -- Sodhi et al. 54 (6): 1155 -- Journal of Antimicrobial Chemotherapy 15 January 2010 5:15 UTC jac.oxfordjournals.org [Source type: Academic]

.Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent.^ Immediate hypersensitivity reactions to b-lactam antibiotics.
  • Cephalosporins can be prescribed safely for penicillin-allergic patients — The Journal of Family Practice 15 January 2010 5:15 UTC www.jfponline.com [Source type: Academic]

^ Diagnosis of immediate allergic reactions to beta-lactam antibiotics.
  • History Of Penicillin 15 January 2010 5:15 UTC www.docstoc.com [Source type: Academic]

^ Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent.

[31] .The allergic reaction is a Type I hypersensitivity reaction.^ Allergic reactions to medications represent a specific class of drug hypersensitivity reactions mediated by IgE .

^ Among the 15 penicillin allergic patients that developed a hypersensitivity reaction, 11 manifested a maculopapular rash as the reaction to the carbapenem.
  • Is it safe to use carbapenems in patients with a history of allergy to penicillin? -- Sodhi et al. 54 (6): 1155 -- Journal of Antimicrobial Chemotherapy 15 January 2010 5:15 UTC jac.oxfordjournals.org [Source type: Academic]

^ These are sometimes termed "non-type I allergic reactions," but they are not IgE mediated and are not truly allergic.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

.Anaphylaxis will occur in approximately 0.01% of patients.^ Several studies suggest that cephalosporin-induced anaphylaxis occurs no more frequently among patients with known penicillin allergy than among those without such allergy.
  • Cephalosporins can be prescribed safely for penicillin-allergic patients — The Journal of Family Practice 15 January 2010 5:15 UTC www.jfponline.com [Source type: Academic]

[27] .It has previously been accepted that there was up to a 10% cross-sensitivity between penicillin-derivatives, cephalosporins, and carbapenems, due to the sharing of the β-lactam ring.^ Cephalosporins (beta lactams, including penicillins) .
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

^ Cross-reactivity between a penicillin and a cephalosporin with the same side chain.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ This likely led to the over-estimation of cross-reactivity between penicillins and cephalosporins.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

[32][33] .However recent assessments have shown no increased risk for cross-allergy for 2nd generation or later cephalosporins.^ [Abstract/ Free Full Text] Assem ESK, Vickers MR. Tests for penicillin allergy in man: the immunological cross-reaction between penicillins and cephalosporins.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ The true increased risk of an allergic reaction to a cephalosporin among penicillin-allergic patients must take into account the possibility of a primary (and unrelated) cephalosporin allergy.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ Swedish investigators also recently reported that co-trimoxazole was the only antibiotic that was associated with a significantly increased risk of carriage of PRSP (OR = 3.48).
  • Penicillin-resistant Streptococcus pneumoniae: selection by both {beta}-lactam and non-{beta}-lactam antibiotics -- Goldstein 44 (2): 141 -- Journal of Antimicrobial Chemotherapy 15 January 2010 5:15 UTC jac.oxfordjournals.org [Source type: Academic]

[34][35] .Recent papers have shown that a major feature in determining immunological reactions is the similarity of the side chain of first generation cephalosporins to penicillins, rather than the β-lactam structure that they share.^ Cross-reactivity between a penicillin and a cephalosporin with the same side chain.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ Penicillins and cephalosporins have similar chemical configurations.
  • A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients -- Pichichero 115 (4): 1048 -- Pediatrics 15 January 2010 5:15 UTC pediatrics.aappublications.org [Source type: Academic]

^ Recent papers have shown that major feature in determining immunological reactions is the similarity of the side chain of first generation cephalosporins to penicillins, rather than the β-lactam structure that they share.

[36]

Production

.Penicillin is a secondary metabolite of fungus Penicillium that is produced when growth of the fungus is inhibited by stress.^ Penicillin or Penicillins are antibiotics that I think are produced by the fungus.
  • Penicillium and Penicillin - Naked Scientists Discussion Forum 15 January 2010 5:15 UTC www.thenakedscientists.com [Source type: FILTERED WITH BAYES]

^ The production of penicillin by the fungus has created a zone of growth inhibition of the bacterium.
  • Penicillin and other antibiotics 15 January 2010 5:15 UTC www.biology.ed.ac.uk [Source type: Academic]

^ In 1928 Alexander Fleming discovered accidentally that a mould (Penicillium notatum) contaminating left over cultures of bacteria was actually inhibiting bacterial growth.
  • Penicillium and Penicillin - Naked Scientists Discussion Forum 15 January 2010 5:15 UTC www.thenakedscientists.com [Source type: FILTERED WITH BAYES]

It is not produced during active growth. .Production is also limited by feedback in the synthesis pathway of penicillin.^ Penicillium chrysogenum has a very active alpha-aminoadipic acid pathway that is used for the synthesis of this precursor of penicillin .

α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-Lysine + β-lactam
.The by-product L-Lysine inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production.^ Patients with penicillin allergy should avoid carbapenems, and caution should be used in prescribing cephalosporins in these patients .

^ Later, it was discovered that it was only the presence of phenylacetic acid in corn steep liquor that en­abled the increase of penicillin production.
  • Fleming, Florey, Chain, and the «Wonder Drug» Penicillin 15 January 2010 5:15 UTC puckeypower.com [Source type: FILTERED WITH BAYES]

^ The results on production of penicillin observed in the previous experiments should correlate with the presence or absence of the penicillin biosynthetic genes pcbAB , pcbC , and penDE in the different strains.
  • Production of Penicillin by Fungi Growing on Food Products: Identification of a Complete Penicillin Gene Cluster in Penicillium griseofulvum and a Truncated Cluster in Penicillium verrucosum -- Laich et al. 68 (3): 1211 -- Applied and Environmental Microbiology 15 January 2010 5:15 UTC aem.asm.org [Source type: Academic]

.The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress and will produce plenty of penicillin.^ This is the species that is currently used to produce penicillin.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ It was much much later during the time of World War II that penicillin was produced in large quantities for medicinal use.
  • Science :: :: Penicillin Discovered 15 January 2010 5:15 UTC www.dimdima.com [Source type: FILTERED WITH BAYES]

^ In the past, multiway principal component analysis (MPCA), a multivariate projection method, has been widely used to monitor batch and fed-batch processes .

.The carbon sources that are available are also important: glucose inhibits penicillin, whereas lactose does not.^ A personal or family history of drug allergies may be relevant as this may predispose to penicillin allergy7 whereas a history of atopy does not.
  • History Of Penicillin 15 January 2010 5:15 UTC www.docstoc.com [Source type: Academic]

^ The sensitivity is approximately 80-90%8 but it does not test for the minor determinants of penicillin.5 More recently the CAST (cellular antigen stimulation test) has become available.
  • History Of Penicillin 15 January 2010 5:15 UTC www.docstoc.com [Source type: Academic]

.The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must be controlled automatically.^ SR1- was grown with L-lysine as the sole nitrogen source and supplemented with DL-alpha-aminoadipic acid, a high level of pipecolic acid accumulated intracellularly .

.Penicillin production emerged as an industry as a direct result of World War II. During the war, there was an abundance of jobs available in the U.S. on the home front.^ In addition, there were problems in the production of penicillin.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ The prevalence of penicillinase-producing strains of S. aureus within hospitals soon began to rise as penicillin became readily available after World War II. Within a few years, most hospital isolates were resistant to penicillin ( 17 ).
  • CDC - The Changing Epidemiology of Staphylococcus aureus? 15 January 2010 5:15 UTC www.cdc.gov [Source type: Academic]

^ 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.
  • Penicillin: Free Encyclopedia Articles at Questia.com Online Library 15 January 2010 5:15 UTC www.questia.com [Source type: Academic]

.The War Production Board was founded to monitor job distribution and production.^ The American War Production Board (WPB) and pri­vate pharmaceutical companies took on the challenge.
  • Fleming, Florey, Chain, and the «Wonder Drug» Penicillin 15 January 2010 5:15 UTC puckeypower.com [Source type: FILTERED WITH BAYES]

[37] .Penicillin was produced in huge quantities during the war and the industry prospered.^ Thus, penicillin was taken from small laboratories to huge medical factories and eventually became one of the most famous antibiotics in the medical industry.

^ By the end of the war, enough penicillin was produced to treat seven million patients/year.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ Fleming only continued to work on and off with with penicillin between 1928-1931, but was unable to produce it in the quantity necessary for testing or practical applications.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

.In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe.^ Yet six years later, he was to begin a program of research that would lead to the mass production of penicillin.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ His research program eventually was the one that led to a method in the purification and mass production of penicillin.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]

^ The American War Production Board (WPB) and pri­vate pharmaceutical companies took on the challenge.
  • Fleming, Florey, Chain, and the «Wonder Drug» Penicillin 15 January 2010 5:15 UTC puckeypower.com [Source type: FILTERED WITH BAYES]

.At the time of this plan, 425 million units per year were being produced.^ By the end of the war, enough penicillin was produced to treat seven million patients/year.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

^ Furthermore, these three trials are cluster trials with the unit of allocation being a time period.
  • Intramuscular penicillin for the prevention of early onset group B streptococcal infection in newborn infants 15 January 2010 5:15 UTC www.nichd.nih.gov [Source type: Academic]

^ These studies include a total of 511 patient treated with 1.2 million units if IM benzathine penicillin for a duration of 6 mos to 12 years.
  • Safety of Long Term Therapy with Penicillin and Penicillin Derivatives 15 January 2010 5:15 UTC www.fda.gov [Source type: Academic]

.As a direct result of the war and the War Production Board, by June 1945 over 646 billion units per year were being produced.^ From January to May 1943, only 400 million units of penicillin had been made; by the time the war ended, U.S. companies were making 650 billion units a month.
  • Science :: :: Penicillin Discovered 15 January 2010 5:15 UTC www.dimdima.com [Source type: FILTERED WITH BAYES]

^ The American War Production Board (WPB) and pri­vate pharmaceutical companies took on the challenge.
  • Fleming, Florey, Chain, and the «Wonder Drug» Penicillin 15 January 2010 5:15 UTC puckeypower.com [Source type: FILTERED WITH BAYES]

^ By the end of the war, enough penicillin was produced to treat seven million patients/year.
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC www.botany.hawaii.edu [Source type: FILTERED WITH BAYES]
  • Penicillin, The Wonder Drug 15 January 2010 5:15 UTC dwb.unl.edu [Source type: FILTERED WITH BAYES]

[38]
.In recent years, the biotechnology method of directed evolution has been applied to produce by mutation a large number of Penicillium strains.^ Although penicillinase-producing strains were universally present in hospitals by the early 1950s, community isolates of S. aureus were considered to be largely penicillin susceptible.
  • CDC - The Changing Epidemiology of Staphylococcus aureus? 15 January 2010 5:15 UTC www.cdc.gov [Source type: Academic]

^ In recent years, the number of available antibiotics has increased dramatically.
  • Penicillin Allergy - Resident Grand Rounds 15 January 2010 5:15 UTC intmedweb.wfubmc.edu [Source type: Academic]

These directed-evolution techniques include error-prone PCR, DNA shuffling, ITCHY, and strand overlap PCR.

See also

References

  1. ^ penicillin at Dorland's Medical Dictionary
  2. ^ "penicillin - Definition from Merriam-Webster's Medical Dictionary". http://medical.merriam-webster.com/medical/penicillin. Retrieved 2009-01-02. 
  3. ^ learnchem.net > Stoichiometry Section: Percent Mass. By Takalah. Retrieved on Jan 9, 2009
  4. ^ Drug Safety > Penicillin G Retrieved on Jan 9, 2009
  5. ^ SymplusWiki > penicillin G Retrieved on Jan 9, 2009
  6. ^ Barbosa S., Taboada P., Ruso J.M., Attwood D., Mosquera V. (August 2003). "Complexes of penicillins and human serum albumin studied by static light scattering". Colloids and Surfaces A: Physicochemical and Engineering Aspects 224: 251–6. doi:10.1016/S0927-7757(03)00322-4. 
  7. ^ a b c Al-Abdallah, Q., Brakhage, A. A., Gehrke, A., Plattner, H., Sprote, P., Tuncher, A. (2004). "Regulation of Penicillin Biosynthesis in Filamentous Fungi". in Brakhage AA. Molecular Biotechnolgy of Fungal beta-Lactam Antibiotics and Related Peptide Synthetases. pp. 45–90. doi:10.1007/b99257. ISBN 3-540-22032-1. 
  8. ^ a b Brakhage, A. A. (1998). "Molecular Regulation of b-Lactam Biosynthesis in Filamentous Fungi". Microbiol Mol Biol Rev. (62): 547–85. 
  9. ^ Baldwin, J. E., Byford, M. F., Clifton, I., Hajdu, J., Hensgens, C., Roach, P, Schofield, C. J. (1997). "Proteins of the Penicillin Biosynthesis Pathway". Curr Opin Struct Biol. (7): 857–64. 
  10. ^ a b Fernandez, F. J., Fierro, F., Gutierrez, S, Kosalkova, K . Marcos, A. T., Martin, J. F., Velasco, J. (September 1994). "Expression of Genes and Processing of Enzymes for the Biosynthesis of Penicillins and Cephalosporms". Anton Van Lee 65 (3): 227–43. doi:10.1007/BF00871951. 
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External links


Simple English

Penicillin is a common antibiotic, used to treat bacterial infections. Penicillin was discovered by Scottish scientist Sir Alexander Fleming in 1928. It was not mass-produced until the 1940s, however. Penicillin is sometimes used to treat syphilis, tonsilitis, meningitis, and pneumonia as well as other diseases. It was commonly used during World War 2. Penicillin was discovered when Fleming discovered a mold that was stopping bacteria from growing on the petri dishes. Australian scientist Howard Walter Florey made the penicillin mould into a medicine. Together with another scientist Ernest Boris Chain, Fleming and Florey were given the Nobel Prize for Medicine in 1945.

Some people are allergic to penicillin. Symptoms include nausea, diarrhea, or rash. Rarely, patients who are allergic to penicillin get a fever, vomit, or have serious skin irritation. Because it is such a popular antibiotic, penicillin is the most common cause of serious allergic reactions to a drug.They are used regulary in hospitals nowdays all thanks to Sir Alexander.


Citable sentences

Up to date as of December 22, 2010

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