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Penicillin core structure
Penicillin (sometimes abbreviated PCN) is a group of beta-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. “Penicillin” is also the informal name of a specific member of the penicillin group Penam Skeleton, which has the molecular formula R-C9H11N2O4S, where R is a variable side chain.


The discovery of penicillin is usually attributed to Scottish scientist Sir Alexander Fleming in 1928, though others had earlier noted the antibacterial effects of Penicillium.

The development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey. 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). The manuscripts explained Picado's experiences between 1915 and 1927 about the inhibitory actions of the fungi of genera Penic. Apparently 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.

Fleming, at his laboratory in St. Mary's Hospital (now one of Imperial College's teaching hospitals) in London, noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold Staphylococcus plate culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a Penicillium mold, now known to be Penicillium notatum. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mold. Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. 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).[1] After further experiments, Fleming was convinced that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931, but restarted some clinical trials in 1934 and continued to try to get someone to purify it until 1940. .[2]

In 1939, Australian scientist Howard Walter Florey and a team of researchers (Ernst Boris Chain, A. D. Gardner, Norman Heatley, M. Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made significant progress in showing the in vivo bactericidal action of penicillin. Their attempts to treat humans failed due to insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert Alexander), but they proved its harmlessness and effect on mice.

A mouldy cantaloupe in a Peoria market in 1941 was found to contain the best and highest quality penicillin after a world-wide search.[3]

Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford. On 1942-03-14 John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin.[4][5]

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Penicillin was being mass-produced in 1944

During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds amongst Allied forces; saving an estimated 12-15% of lives. Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug necessitating frequent dosing. Penicillins are actively secreted and about 80% of a penicillin dose is cleared within three to four hours of administration. During those times it became common procedure to collect the urine from patients being treated so that the penicillin could be isolated and reused.[6]

This was not a satisfactory solution, however, so researchers looked for a way to slow penicillin secretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for secretion such that the transporter would preferentially secrete the competitive inhibitor. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity. The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined.<ref name="Silverthorn2004" />Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins.[7]

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

Developments from penicillin

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.

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 methicillin. 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.

The line of true penicillins were 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 importantly, the cephalosporins, have this at the centre of their structures.

Mechanism of action

β-lactam antibiotics work by inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall. The β-lactam moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the peptidoglycan molecules in bacteria, and this weakens the cell wall of the bacterium (in other words, the antibiotic causes cytolysis or death due to osmotic pressure). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and auto lysins which further digest the bacteria's existing peptidoglycan.

Gram-positive bacteria are called protoplasts when they lose their cell wall. Gram-negative bacteria do not lose their cell wall completely and are called spheroplasts after treatment with penicillin.

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. This results in a lowered MBC for susceptible organisms.

Variants in clinical use

The term “penicillin” is often used generically to refer to one of the narrow-spectrum penicillins, particularly benzylpenicillin.

Benzathine benzylpenicillin

Benzathine benzylpenicillin (rINN), also known as benzathine penicillin, is slowly absorbed into the circulation, after intramuscular injection, and hydrolysed to benzylpenicillin in vivo. It is the drug-of-choice when prolonged low concentrations of benzylpenicillin are required and appropriate, allowing prolonged antibiotic action over 2–4 weeks after a single IM dose. It is marketed by Wyeth under the trade name Bicillin L-A.

Specific indications for benzathine pencillin include:[7]

Benzylpenicillin (penicillin G)

Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. Penicillin G is typically given by a parenteral route of administration (not orally) because it is unstable in the hydrochloric acid of the stomach. Because the drug is given parenterally, higher tissue concentrations of penicillin G can be achieved than is possible with phenoxymethylpenicillin. These higher concentrations translate to increased antibacterial activity.

Specific indications for benzylpenicillin include:[7]

Phenoxymethylpenicillin (penicillin V)

Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin, however, and is only appropriate in conditions where high tissue concentrations are not required.

Specific indications for phenoxymethylpenicillin include:[7] Penicillin V is the first choice in the treatment of odontogenic infections.

Procaine benzylpenicillin

Procaine benzylpenicillin (rINN), also known as procaine penicillin, is a combination of benzylpenicillin with the local anaesthetic agent procaine. Following deep intramuscular injection, it is slowly absorbed into the circulation and hydrolysed to benzylpenicillin — thus it is used where prolonged low concentrations of benzylpenicillin are required.

This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin. It is widely used in veterinary settings.

Specific indications for procaine penicillin include:[7]
  • Syphilis
  • It should be noted that in the United States, Bicillin C-R (a injectable suspension which 1.2 million units of benzathine penicillin & 1.2 million units of procaine penicillin per 4 mL) is not recommended for treating syphilis, since it contains only half the recommended dose of benzathine penicillin. Medication errors have been made due to the confusion between Bicillin L-A & Bicillin C-R.[8] As a result, changes in product packaging have been made; specifically, the statement "Not for the Treatment of Syphilis" has been added in red text to both the Bicillin CR and Billin CR 900/300 syringe labels.[9]
  • Respiratory tract infections where compliance with oral treatment is unlikely
  • Cellulitis, erysipelas
Procaine penicillin is also used as an adjunct in the treatment of anthrax.

Semi-synthetic penicillins

Structural modifications were made to the side chain of the penicillin nucleus in an effort to improve oral bioavailability, improve stability to beta-lactamase activity, and increase the spectrum of action.

Narrow spectrum penicillinase-resistant penicillins

This group was developed to be effective against beta-lactamases produced by Staphylococcus aureus, and are occasionally known as anti-staphylococcal penicillin. Penicillin is rampantly used for curing infections and to prevent growth of harmful mold.

Narrow spectrum β-lactamase-resistant penicillins

This molecule has a spectrum directed towards Gram negative bacteria without activity on Pseudomonas aeruginosa or Acinetobacter spp. with remarkable resistance to any type of β-lactamase.

Moderate spectrum penicillins

This group was developed to increase the spectrum of action and, in the case of amoxicillin, improve oral bioavailability. And the prodrugs of ampicillin that are converted in the body to ampicillin:

Extended Spectrum Penicillins

This group was developed to increase efficacy against Gram-negative organisms. Some members of this group also display activity against Pseudomonas aeruginosa. These are divided into carboxypencillins and ureidopenicillins.

Carboxypencillins Ureidopenicillins

Penicillins with beta-lactamase inhibitors

Penicillins may be combined with beta-lactamase inhibitors to increase efficacy against β-lactamase-producing organisms. The addition of the beta-lactamase inhibitor does not generally, in itself, increase the spectrum of the partner penicillin.

Other Penicillins

  • Metampicillin
  • Broadcillin
  • Epicillin
  • Ampicillin benzathine
  • Talampicillin
  • Combipenix
  • Ampicillinoic acid
  • N-(N'-Methylasparaginyl)amoxicillin
  • Aspoxicillin
  • N-Propionylampicillin
  • Lenampicillin
  • Sulacillin

Adverse effects

Adverse drug reactions

Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include: diarrhea, nausea, rash, urticaria, and/or superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of patients) include: fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in epileptics) and/or pseudomembranous colitis.<ref name="AMH2006" />

Pain and inflammation at the injection site is also common for parenterally-administered benzathine benzylpenicillin, benzylpenicillin, and to a lesser extent procaine benzylpenicillin.


Although penicillin is still the most commonly reported allergy, less than 20% of all patients who believe that they have a penicillin allergy are truly allergic to penicillin;[10] nevertheless, penicillin is still the most common cause of severe allergic drug reactions.

Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients.<ref name="AMH2006" /> There is about a 5% cross-sensitivity between penicillin-derivatives, cephalosporins and carbapenems.[11] This risk warrants extreme caution with all β-lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.

See also


1. ^ Flemming A. (1929). "On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ.". Br J Exp Pathol 10 (31): 226–36. 
2. ^ Brown, Kevin. (2004). Penicillin Man: Alexander Fleming and the Antibiotic Revolution.. Stroud: Sutton. ISBN 0-7509-3152-3. 
3. ^ [1]
4. ^ Saxon, W.. "Anne Miller, 90, first patient who was saved by penicillin", The New York Times, 1999-06-09. 
5. ^ Krauss K, editor (1999). Yale-New Haven Hospital Annual Report (PDF). Yale-New Haven Hospital.
6. ^ Silverthorn, DU. (2004). Human physiology: an integrated approach.. Upper Saddle River (NJ): Pearson Education. ISBN 0-8053-5957-5. 
7. ^ (2006) in Rossi S, editor: Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3. 
8. ^ (2005) "Inadvertent use of Bicillin C-R to treat syphilis infection--Los Angeles, California, 1999-2004". MMWR Morb. Mortal. Wkly. Rep. 54 (9): 217-9. PMID 15758893. 
9. ^ United States Food & Drug Administration. "FDA Strengthens Labels of Two Specific Types of Antibiotics to Ensure Proper Use." Published December 1, 2004. Last accessed June 18, 2007.
10. ^ Salkind AR, Cuddy PG, Foxworth JW (2001). "Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy". JAMA 285 (19): 2498–2505. 
11. ^ Gruchalla RS, Pirmohamed M (2006). "Clinical practice. Antibiotic allergy". N. Engl. J. Med. 354 (6): 601-9. DOI:10.1056/NEJMcp043986. PMID 16467547. 
Penicillin is a Japanese rock band formed in 1992.


Formed by friends at Tokai University in Kanagawa, Japan on February 14, 1992 Penicillin went on to become one of the largest acts in the Japanese Visual Kei scene and is still thriving today, fifteen years later.
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β-lactam antibiotics are a broad class of antibiotics which include penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure.
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An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply (usually at the expense of the host).
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Gram-positive bacteria are those that retain a crystal violet dye during the Gram stain process.[1] Gram-positive bacteria appear blue or violet under a microscope, while Gram-negative bacteria appear red or pink.
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A beta-lactam ring (β-lactam) or penam is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom. The beta-lactam ring is part of the structure of several antibiotic families, principally the penicillins, cephalosporins,
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side chain in organic chemistry and biochemistry is a part of a molecule that is attached to a core structure. An R group is a generic label for a side chain which can be anything; however, it is typically stable and covalently linked to the adjoining atom.
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Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish biologist and pharmacologist. Fleming published many articles on bacteriology, immunology, and chemotherapy.
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Howard Walter Florey, Baron Florey, OM, FRS, (September 24, 1898 – February 21, 1968) was a pharmacologist who shared the Nobel Prize for Physiology or Medicine in 1945 with Ernst Boris Chain and Sir Alexander Fleming for his role in the extraction of penicillin.
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¡Vivan siempre el trabajo y la paz!   (Spanish)
"May Work And Peace Live Forever"
Noble patria, tu hermosa bandera   (Spanish)
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Clodomiro Picado Twight, also known as Clorito Picado, was a Latin American pioneer in toxicology.

He published some 115 research papers in his lifetime, delving into nearly all aspects of his environment: soil, flora, fauna, human tissues, water, plant pathology and
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Imperial College London (officially Imperial College of Science, Technology and Medicine) is a British university in London. Imperial's teaching and research have traditionally focused on science, engineering and medicine, although more recently its faculties in these areas
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Molds (or moulds, see spelling differences) include all species of microscopic fungi that grow in the form of multicellular filaments, called hyphae.[1] In contrast, microscopic fungi that grow as single cells are called yeasts.
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Rosenbach 1884


S. afermentans
S. aureus
S. auricularis
S. capitis
S. caprae
S. cohnii
S. epidermidis
S. felis
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Penicillium bilaiae
Penicillium camemberti
Penicillium candida
Penicillium claviforme
Penicillium crustosum
Penicillium glaucum
Penicillium marneffei
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P. chrysogenum

Binomial name
Penicillium chrysogenum

Penicillium chrysogenum
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filter is a device (usually a membrane or layer) that is designed to block certain objects or substances while letting others through. Filters are often used to remove harmful substances from air or water, for example to remove air pollution, to make water drinkable, to prepare
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A microbiological culture, or microbial culture, is a method of growing a microbial organism to determine what it is, its abundance in the sample being tested, or both. It is one of the primary diagnostic methods of microbiology.
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Gram-positive bacteria are those that retain a crystal violet dye during the Gram stain process.[1] Gram-positive bacteria appear blue or violet under a microscope, while Gram-negative bacteria appear red or pink.
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Gram-negative bacteria are those that do not retain crystal violet dye in the Gram staining protocol.[1] Gram-positive bacteria will retain the dark blue dye after an alcohol wash.
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Haemophilus influenzae
Classification & external resources

ICD-10 A 49.2
ICD-9 041.5

Haemophilus influenzae

H. influenzae on a blood agar plate.

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Advance Australia Fair [1]

Capital Canberra

Largest city Sydney
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Howard Walter Florey, Baron Florey, OM, FRS, (September 24, 1898 – February 21, 1968) was a pharmacologist who shared the Nobel Prize for Physiology or Medicine in 1945 with Ernst Boris Chain and Sir Alexander Fleming for his role in the extraction of penicillin.
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Sir Ernst Boris Chain (June 19, 1906 – August 12, 1979) was a German-born British biochemist, and a 1945 co-recipient of the Nobel Prize for Physiology or Medicine for his work on penicillin.
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Arthur Duncan Gardner (1884 - 1977) was a member of the team of Oxford University scientists who developed penicillin and was Regius Professor of Medicine at Oxford from 1948 to 1954.
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Norman George Heatley (January 10, 1911 – January 5, 2004) was a member of the team of Oxford University scientists who developed penicillin.

He was born in Woodbridge, Suffolk, and as a boy was an enthusiastic sailor of a small boat on the River Deben; an experience
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University of Oxford (usually abbreviated as Oxon. for post-nominals, from "Oxoniensis"), located in the city of Oxford, England, is the oldest university in the English-speaking world.
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In vivo (Latin: (with)in the living) means that which takes place inside an organism. In science, in vivo refers to experimentation done in or on the living tissue of a whole, living organism as opposed to a partial or dead one.
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Reserve Constable Albert Alexander (c. 1873 – 15 March 1941), the first patient to be treated with penicillin.

Albert Alexander was a constable in the police force of the County of Oxford, England.
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Oxford Radcliffe Hospitals NHS Trust

Place Oxford, Oxfordshire, England, (UK)

Care System Public NHS
Hospital Type Specialist

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