Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have An infection is the detrimental Colonization of a host Organism by a foreign Species. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. “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. ||-||-||-||-||-||-||}A beta-lactam ring ( β -lactam or penam is a Lactam with a Heteroatomic Ring structure, consisting of three A side chain in Organic chemistry and Biochemistry is a part of a Molecule that is attached to a core structure

Contents 1 Discovery and history 2 Developments from penicillin 3 Mechanism of action 4 Variants in clinical use 5 Adverse effects 6 Production 7 See also 8 References

Discovery and history

The discovery of penicillin is 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. Alexander Fleming was the first to suggest that the Penicillium mould must have an antibacterial substance and the first to isolate the active substance which Sir Alexander Fleming (6 August 1881 &ndash 11 March 1955 was a Scottish Biologist and Pharmacologist. Howard Walter Florey Baron Florey, OM, FRS, ( September 24, 1898 &ndash February 21, 1968) was an Australian

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^[1]. The Royal Society of London for the Improvement of Natural Knowledge, known simply as The Royal Society, is a Learned society for science that was founded in 1660 John Tyndall FRS ( August 2, 1820 &ndash December 4, 1893) was a prominent 19th century Irish Physicist. Ernest Duchesne documented it in his 1897 paper; however it was not accepted by the Institut Pasteur because of his young age. Ernest Duchesne ( May 30, 1874 – April 12, 1912) was a French Physician who noted that certain moulds kill bacteria 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). Costa Rica, officially the Republic of Costa Rica ( Spanish: Costa Rica or República de Costa Rica,) is a Country in UserKurt Shaped Box was consulted before re-creating it from scratch The manuscripts explained Picado's experiences between 1915 and 1927 about the inhibitory actions of the fungi of genera Penic. 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.

Fleming recounted later that the date of his breakthrough was on the morning of Tuesday, September 28, 1928^[2]. Events 48 BC - Pompey the Great is assassinated on orders of King Ptolemy of Egypt after landing in Egypt. Year 1928 ( MCMXXVIII) was a Leap year starting on Sunday (link will display full calendar of the Gregorian calendar. At his laboratory in the basement of St. Mary's Hospital in London (now part of Imperial College), Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold Staphylococcus plate culture. Imperial College London (officially The Imperial College of Science Technology and Medicine as given in its Royal Charter It is one of only three universities to have reached WikipediaManual_of_Style#National_varieties_of_English --> Molds (or Staphylococcus (in Greek σταφυλη staphyle means bunch of grapes and κοκκος coccos means granule is a genus of Gram-positive Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic He grew a pure culture of the mold and discovered that it was a Penicillium mold, now known to be Penicillium notatum. Penicillium (from Latin penicillus: paintbrush) is a Genus of Ascomyceteous Fungi that includes Penicillium chrysogenum is a mold that is widely distributed in nature and is often found living on foods and in indoor environments Charles Thom, an American specialist working at the U. S. Department of Agriculture, was the acknowledged expert, and Fleming referred the matter to him. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mold. In Chemistry and common usage a filter is a device (usually a membrane or layer that is designed A microbiological culture, AKA microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol 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)^[3]. Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, is a non-motile Gram-negative Coccobacillus 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^[4].

In 1930 Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to treat sycosis - eruptions in beard follicles - but was unsuccessful, probably because the drug did not get deep enough. Moving on to ophthalmia neonatorum - a gonococcal infection in babies - he achieved the first cure on 25 November 1930. He cured four patients (one adult, three babies) of eye infections, although a fifth patient was not so lucky^[5].

In 1939, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain, A. D. Gardner, Norman Heatley, M. For a topic outline on this subject see List of basic Australia topics. Howard Walter Florey Baron Florey, OM, FRS, ( September 24, 1898 &ndash February 21, 1968) was an Australian Sir Ernst Boris Chain ( June 19, 1906 &ndash August 12, 1979) was a German -born British biochemist and a 1945 co-recipient Arthur Duncan Gardner (1884 - 1977 was a member of the team of Oxford University scientists who developed Penicillin and was Regius Professor of Medicine Norman George Heatley ( 10 January 1911 &ndash 5 January 2004) was a member of the team of Oxford University scientists who developed 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. The University of Oxford (informally "Oxford University" or simply "Oxford" located in the city of Oxford, Oxfordshire, England is the In vivo ( Latin: within the living means that which takes place inside an organism. 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^[6]. Reserve Constable Albert Alexander (c 1873– 15 March 1941) the first Patient to be treated with Penicillin.

Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford. The Radcliffe Infirmary was a hospital in central Oxford, England, located at the southern end of Woodstock Road on the western side backing onto On March 14, 1942, John Bumstead and Orvan Hess became the first in the world to successfully treat a patient using penicillin^[7][8]. Events 1489 - The Queen of Cyprus, Catherine Cornaro, sells her kingdom to Venice. Year 1942 ( MCMXLII) was a Common year starting on Thursday (the link will display the full 1942 calendar of the Gregorian calendar. Orvan Walter Hess ( June 18, 1906 – September 6, 2002) was a physician noted for his early use of Penicillin and the development

The challenge of mass-producing the drug had been daunting. On March 14, 1942 the first patient was successfully treated for streptococcal septicemia with U. Events 1489 - The Queen of Cyprus, Catherine Cornaro, sells her kingdom to Venice. Year 1942 ( MCMXLII) was a Common year starting on Thursday (the link will display the full 1942 calendar of the Gregorian calendar. S. -made penicillin. Half of the total supply produced at the time was used on that one patient. By June 1942 there was just enough U. S. penicillin available to treat ten patients^[9]. 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^[10]. Cantaloupe (also cantaloup) refers to two varieties of Muskmelon ( Cucumis melo), which is a Species in the family Cucurbitaceae (a 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.

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. World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including In general allies are people groups or nations that have joined together in an association for mutual benefit or to achieve some common purpose 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. The kidneys are complicated organs that have numerous biological roles 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^[11].

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. Uricosuric Medications ( Drugs are substances that increase the excretion of Uric acid in the Urine, thus reducing uric acid concentrations in Probenecid is a Uricosuric drug primarily used in treating Gout or Hyperuricemia, that increases uric acid removal in the urine When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing penicillin's concentration and prolonging its activity. The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined. ^[11] Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins^[12].

The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s. Chemical structure refers to Molecular geometry, Electronic structure and Crystal structure. Dorothy Crowfoot Hodgkin, born Dorothy Mary Crowfoot OM, FRS ( 12 May 1910 &ndash 29 July 1994) was a British A team of Oxford research scientists led by Australian Howard Florey, Baron Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass-producing the drug. Howard Walter Florey Baron Florey, OM, FRS, ( September 24, 1898 &ndash February 21, 1968) was an Australian Sir Ernst Boris Chain ( June 19, 1906 &ndash August 12, 1979) was a German -born British biochemist and a 1945 co-recipient Norman George Heatley ( 10 January 1911 &ndash 5 January 2004) was a member of the team of Oxford University scientists who developed 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. John Sheehan (1844 – 12 June 1885) was a 19th century New Zealand politician 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. The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. For a topic outline on this subject see List of basic Australia topics. Penicillin has since become the most widely-used antibiotic to date, and is still used for many Gram-positive bacterial infections. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining.

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 first major development was ampicillin, which offered a broader spectrum of activity than either of the original penicillins. Ampicillin is a beta-lactam Antibiotic that has been used extensively to treat bacterial Infections since 1961 Further development yielded beta-lactamase-resistant penicillins including flucloxacillin, dicloxacillin and methicillin. Beta-lactamases are Enzymes ( produced by some bacteria and are responsible for their resistance to Beta-lactam antibiotics like Penicillins Flucloxacillin ( INN) or floxacillin ( USAN) is a narrow spectrum Beta-lactam antibiotic of the Penicillin class Dicloxacillin ( INN) is a narrow spectrum Beta-lactam antibiotic of the Penicillin class Meticillin ( INN, BAN) or methicillin ( USAN) is a narrow spectrum Beta-lactam antibiotic of the Penicillin class 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 was the antipseudomonal penicillins, such as ticarcillin and piperacillin, useful for their activity against Gram-negative bacteria. Ticarcillin is a Carboxypenicillin. It is almost invariably sold and used in combination with Clavulanate as Timentin. Piperacillin is an extended spectrum beta-lactam Antibiotic of the Ureidopenicillin class Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most important, the cephalosporins, have this at the center of their structures. Carbapenems are a class of Beta-lactam antibiotics with a broad spectrum of antibacterial activity and have a structure which renders them highly resistant to Beta-lactamases The cephalosporins (ˌsɛfələˈspɔrən/ /ˌkɛfə- are a class of β-lactam antibiotics. Ondred Abumbumer also made further discoveries towards penicillin ^[13]

Mechanism of action

Main article: beta-lactam antibiotic

β-lactam antibiotics work by inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall. β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems Not to be confused with Glycoprotein. Peptidoglycan, also known as murein, is a Polymer consisting of sugars and amino Cross-links are bonds that link one Polymer chain to another They can be Covalent bonds or Ionic bonds "Polymer chains" can refer A cell wall is a tough flexible and sometimes fairly rigid layer surrounding a cell, located external to the Cell membrane, which provides the cell with structural 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). ||-||-||-||-||-||-||}A beta-lactam ring ( β -lactam or penam is a Lactam with a Heteroatomic Ring structure, consisting of three In Organic chemistry, functional groups are specific groups of Atoms within Molecules that are responsible for the characteristic Chemical reactions Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins A transpeptidase (EC 34164 is a Bacterial Enzyme that Cross-links the Peptidoglycan chains to form rigid Cell walls This enzyme Cytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to move into the cell Death is the termination of the biological functions that define living Organisms It refers both to a specific Osmosis is the Diffusion of a solvent (frequently water through a semi-permeable membrane, from a solution of low solute concentration (high water potential 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.

Gram-positive bacteria are called protoplasts when they lose their cell wall. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This article discusses protoplasts in the biological sense For the theological use see Adam and Eve Protoplast, from the Ancient Greek Gram-negative bacteria do not lose their cell wall completely and are called spheroplasts after treatment with penicillin. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol A spheroplast is a cell from which the Cell wall has been almost completely removed as by the action of 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. An aminoglycoside is a molecule composed of a sugar group and an Amino group This results in a lowered MBC for susceptible organisms. The Minimum Bactericidal Concentration (MBC is the lowest concentration of antibiotic required to kill an organism

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 (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections

Penicillin G
Systematic (IUPAC) name
4-Thia-1-azabicyclo(3. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general 2. 0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-((phenylacetyl)amino)- (2S-(2α,5α,6β))-
Identifiers
CAS number	61-33-6
ATC code	?
PubChem	?
Chemical data
Formula	C16H18N2O4S
Mol. mass	334. CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 4 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	parenteral

Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. For other uses of the words gram or gramme see Gram (disambiguation. The mole (symbol mol) is a unit of Amount of substance: it is an SI base unit, and almost the only unit to be used to measure this In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route In Pharmacology and Toxicology, a route In Medicine, a gold standard test or criterion standard test is a Diagnostic test or benchmark that is regarded as definitive Penicillin G is typically given by a parenteral route of administration (not orally) because it is unstable in the hydrochloric acid of the stomach. In Pharmacology and Toxicology, a route Hydrochloric acid is the Solution of Hydrogen chloride ( H[[Chlorine Cl]] in water 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:^[12]

• Cellulitis
• Bacterial endocarditis
• Gonorrhea
• Meningitis
• aspiration pneumonia, lung abscess
• Community-acquired pneumonia
• Syphilis
• Septicemia in children

Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. Cellulitis is an Infection of the deep Subcutaneous tissue of the Skin. Endocarditis is an Inflammation of the inner layer of the Heart, the Endocardium. Gonorrhea (also gonorrhoea) caused by the bacteria Neisseria gonorrhoeae, is a common Sexually transmitted disease. Meningitis is Inflammation of the protective membranes covering the Brain and Spinal cord, known collectively as the Meninges. Aspiration pneumonia is Bronchopneumonia that develops due to the entrance of foreign materials that enter the bronchial tree usually oral or gastric contents (including food An abscess (abscessus is a collection of Pus (dead Neutrophils) that has accumulated in a cavity formed by the tissue on the basis of an infectious process Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused It is less active than benzylpenicillin, however, and is appropriate only in conditions where high tissue concentrations are not required.

Specific indications for phenoxymethylpenicillin include:^[12]

• Infections caused by Streptococcus pyogenes
  • Tonsillitis
  • Pharyngitis
  • Skin infections
• Prophylaxis of rheumatic fever
• Moderate-to-severe gingivitis (with metronidazole)

Penicillin V is the first choice in the treatment of odontogenic infections. Streptococcus pyogenes is a spherical Gram-positive Bacteria that grows in long chains and is the cause of Group A streptococcal infections Tonsillitis is an Infection of the Tonsils and will often but not necessarily cause a Sore throat and Fever. See also Strep throat. Pharyngitis (ˌfarɪnˈdʒʌɪtɪs is in most cases a Painful inflammation of the Pharynx, and is The skin is the outer covering of living tissue of an animal (or plant Rheumatic fever is an Autoimmune inflammatory Disease which may develop two to three weeks after a Group A streptococcal infection (such as Metronidazole ( INN) (mɛtrəˈnaɪdəzoʊl is a Nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible

Procaine benzylpenicillin (rINN), also known as procaine penicillin, is a combination of benzylpenicillin with the local anaesthetic agent procaine. An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed A local anesthetic is a drug that causes reversible Local anesthesia and a loss of Nociception. Procaine is a Local anesthetic drug of the Amino Ester group It is used primarily to reduce the pain of Intramuscular injection of 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. Intramuscular injection is the injection of a substance directly into a Muscle. Hydrolysis is a Chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions which may go on to participate in further reactions

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

Specific indications for procaine penicillin include:^[12]

• Syphilis
  • It should be noted that in the United States, Bicillin C-R (a injectable suspension which 1. Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. 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. ^[14] 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. ^[15]
• 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. In humans the respiratory tract is the part of the Anatomy that has to do with the process of respiration. Cellulitis is an Infection of the deep Subcutaneous tissue of the Skin. Erysipelas ( Greek ερυσίπελας - red skin) is an acute Streptococcus Bacterial infection of the Dermis, resulting in inflammation Anthrax is an acute Disease in humans and animals caused by the bacterium Bacillus anthracis which is highly lethal in some forms

Benzathine benzylpenicillin (rINN), also known as benzathine penicillin, is slowly absorbed into the circulation, after intramuscular injection, and hydrolysed to benzylpenicillin in vivo. Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Intramuscular injection is the injection of a substance directly into a Muscle. 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 penicillin include:^[12]

• Prophylaxis of rheumatic fever
• Early or latent syphilis

Adverse effects

Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include diarrhea, hypersensitivity, nausea, rash, neurotoxicity urticaria, and/or superinfection (including candidiasis). Rheumatic fever is an Autoimmune inflammatory Disease which may develop two to three weeks after a Group A streptococcal infection (such as Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Candidiasis, commonly called yeast infection or thrush, is a Fungal infection (mycosis of any of the Candida species of which Infrequent adverse effects (0. 1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in epileptics), and/or pseudomembranous colitis. Erythema is redness of the Skin caused by Capillary congestion Angioedema ( BE: angiooedema) also known by its Eponym Quincke's edema, is the rapid swelling ( Edema) of the Dermis ^[12]

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

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;^[16] 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. Allergy is a disorder of the Immune system often also referred to as Atopy. ^[17] Anaphylaxis will occur in approximately 0. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals 01% of patients. ^[12] 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. ^[18][19] However recent assessments have shown no increased risk for cross-allergy for 2nd generation or later cephalosporins. ^[20][21] 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. ^[22]

Production

The production of penicillin is an area that requires scientists and engineers to work together to achieve the most efficient way of producing large amounts of penicillin.

Penicillin is a secondary metabolite of fungus Penicillium, which means the fungus will not produce the antibiotics while it is growing, but will produce penicillin when it feels threatened. There are also other factors that inhibit penicillin production. One of these factors is the synthesis pathway of penicillin:

α-ketoglutarate + AcCoA -> homocitrate -> L-α-aminoadipic acid -> L-Lysine + β-lactam

It turns out that the by-product L-Lysine will inhibit the production of homocitrate, so the presence of exogenous lysine should be avoided in the penicillin production.

The penicillium cells are grown using a technique called fed-batch culture; this way the cells are constantly subject to stress and will produce plenty of penicillin. A fed-batch is a biotechnological Batch process which is based on feeding of a growth limiting nutrient substrate to a culture The carbon sources that are available are also important: Glucose will inhibit penicillin, whereas lactose does not. The pH level, nitrogen level, Lysine level, Phosphate level, and oxygen availability of the batches must be controlled automatically.

Other area of biotechnology such as directed evolution can also be applied to mutate the strains into producing a much larger number of penicillin. Directed evolution is a method used in Protein engineering to harness the power of Natural selection to evolve Proteins or RNA with desirable These directed-evolution techniques include error-prone PCR, DNA shuffling, ITCHY, and strand over-lap PCR.

See also

• β-Lactam antibiotic
• History of Development of Penicillin Article
• Model of Structure of Penicillin, by Dorothy Hodgkin et al., Museum of the History of Science, Oxford

Penicillin production emerged as an industry as a direct result of World War II. β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems During the time of war, there was an abundance of jobs available on the homefront. A War Production Board was made to monitor job distribution and production ^[23]. Penicillin production was a huge surplus during the time of the war especially with all the available jobs and the industry prospered. In July, 1943, the War Production Board had set up a plan to distribute mass stock of penicillin to troops fighting in Europe. At the time of this plan, 425 million units were being produced. As a direct result of the war and the War Production Board, by June 1945, over 646 billion units were being produced ^[24].

References

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