Penicillin

Penicillin (PCN or pen) is a group of antibiotics which include penicillin G (intravenous use), penicillin V (use by mouth), procaine penicillin, and benzathine penicillin (intramuscular use). Penicillin antibiotics were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today, though many types of bacteria have developed resistance following extensive use.

About 10% of people report that they are allergic to penicillin; however, up to 90% of this group may not actually be allergic.[2] Serious allergies only occur in about 0.03%.[2] All penicillins are β-lactam antibiotics.

Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming.[3] People began using it to treat infections in 1942.[4] There are several enhanced penicillin families which are effective against additional bacteria; these include the antistaphylococcal penicillins, aminopenicillins and the antipseudomonal penicillins. They are derived from Penicillium fungi.[5]

Penicillin
Penicillin core
Penicillin core structure, where "R" is the variable group
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • US: B (No risk in non-human studies) [1]
Routes of
administration
Intravenous, intramuscular, by mouth
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolismliver
Elimination half-lifebetween 0.5 and 56 hours
ExcretionKidneys
Identifiers
ChemSpider
  • none
Chemical and physical data
FormulaC9H11N2O4S
Molar mass243.26 g·mol−1

Medical uses

The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G, the original penicillin found in 1928), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer period of time. Phenoxymethylpenicillin is less active against gram-negative bacteria than benzylpenicillin.[6][7] Benzylpenicillin, procaine penicillin and benzathine penicillin can only be given by intravenous or intramuscular injections, but phenoxymethylpenicillin can be given by mouth because of its acidic stability.[8]

Susceptibility

While the number of penicillin-resistant bacteria is increasing, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria, including Streptococci, Staphylococci, Clostridium, Neisseria, and Listeria genera. The following list illustrates minimum inhibitory concentration susceptibility data for a few medically significant bacteria:[9][10]

  • Listeria monocytogenes: from less than or equal to 0.06 μg/ml to 0.25 μg/ml
  • Neisseria meningitidis: from less than or equal to 0.03 μg/ml to 0.5 μg/ml
  • Staphylococcus aureus: from less than or equal to 0.015 μg/ml to more than 32 μg/ml

Side effects

Common (≥ 1% of people) adverse drug reactions associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis.[11] Penicillin can also induce serum sickness or a serum sickness-like reaction in some individuals. Serum sickness is a type III hypersensitivity reaction that occurs one to three weeks after exposure to drugs including penicillin. It is not a true drug allergy, because allergies are type I hypersensitivity reactions, but repeated exposure to the offending agent can result in an anaphylactic reaction. Allergy will occur in 1-10% of people, presenting as a skin rash after exposure. IgE mediated Anaphylaxis will occur in approximately 0.01% of patients.[12][11]

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

Members

Names Method of administration Notes
Penicillin G, benzylpenicillin IV or IM It has high urinary excretion and is produced as a salt of potassium or sodium.
Penicillin V, phenoxymethylpenicillin By mouth It is less active than benzylpenicillin against Gram-negative bacteria.
Benzathine benzylpenicillin, benzathine penicillin G IM Benzathine is a stabilizer that causes slower release over two to four weeks.
Procaine benzylpenicillin, penicillin G procaine IM Slow release.

Natural penicillins

β-lactamase-resistant

Aminopenicillins

Carboxypenicillins

Ureidopenicillins

β-lactamase inhibitors

Pharmacology

Penicillin inhibits activity of enzymes that are needed for the cross linking of peptidoglycans in bacterial cell walls, which is the final step in cell wall biosynthesis. It does this by binding to penicillin binding proteins with the beta-lactam ring, a structure found on penicillin molecules. [13][14]. This causes the cell wall to weaken due to fewer cross links and means water uncontrollably flows into the cell because it cannot maintain the correct osmotic gradient. This results in cell lysis and death.

Some bacteria produce enzymes that breakdown the beta-lactam ring, called beta-lactamases, which make the bacteria resistant to penicillin. Therefore, some penicillins are modified or given with other drugs for use against antibiotic resistant bacteria or in immunocompromised patients. Use of clavulanic acid or tazobactam, beta-lactamase inhibitors, alongside penicillin gives penicillin activity against beta-lactamase producing bacteria. Beta lactamase inhibitors irreversibly bind to beta-lactamase preventing it breaking down on beta lactam rings on the antibiotic molecule. Alternatively, flucloxacillin is a modified penicillin that has activity against beta-lactamase producing bacteria due to an acyl side chain that protects the beta lactam ring form beta lactamase. [12]

Mechanism of action

Penicillin spheroplast generation horizontal
Bacteria that attempt to grow and divide in the presence of penicillin fail to do so, and instead end up shedding their cell walls.
Penicillin inhibition
Penicillin and other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.

Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links in the bacterial cell wall; this is achieved through binding of the four-membered β-lactam ring of penicillin to the enzyme DD-transpeptidase. As a consequence, DD-transpeptidase cannot catalyze formation of these cross-links, and an imbalance between cell wall production and degradation develops, causing the cell to rapidly die.

The enzymes that hydrolyze the peptidoglycan cross-links continue to function, even while those that form such cross-links do not. This weakens the cell wall of the bacterium, and osmotic pressure becomes increasingly uncompensated—eventually causing cell death (cytolysis). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the cell wall's peptidoglycans. The small size of the penicillins increases their potency, by allowing them to penetrate the entire depth of the cell wall. This is in contrast to the glycopeptide antibiotics vancomycin and teicoplanin, which are both much larger than the penicillins.[15]

Gram-positive bacteria are called protoplasts when they lose their cell walls. Gram-negative bacteria do not lose their cell walls 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 their disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for susceptible organisms.[16]

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. 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.[17]

The chemical structure of penicillin is triggered with a very precise, pH-dependent directed mechanism, effected by a unique spatial assembly of molecular components, which can activate by protonation. It can travel through bodily fluids, targeting and inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria, meanwhile avoiding the surrounding non-targets. Penicillin can protect itself from spontaneous hydrolysis in the body in its anionic form, while storing its potential as a strong acylating agent, activated only upon approach to the target transpeptidase enzyme and protonated in the active centre. This targeted protonation neutralizes the carboxylic acid moiety, which is weakening of the β-lactam ring N–C(=O) bond, resulting in a self-activation. Specific structural requirements are equated to constructing the perfect mouse trap for catching targeted prey.[18]

Pharmacokinetics

Penicillin has low protein binding in plasma, the bioavailability of penicillin depends on the type; penicillin G has a low bioavailability, below 30%, whereas penicillin V has a higher bioavailability between 60 and 70%. Penicillin has a short half life and is excreted via the kidneys.[19]

Structure

Penicillin-G 3D
Chemical structure of Penicillin G. The sulfur and nitrogen of the five-membered thiazolidine ring are shown in yellow and blue respectively. The image shows that the thiazolidine ring and fused four-membered β-lactam are not in the same plane.

The term "penam" is used to describe the common core skeleton of a member of the penicillins. This core has the molecular formula R-C9H11N2O4S, where R is the variable side chain that differentiates the penicillins from one another. The penam core has a molar mass of 243 g/mol, with larger penicillins having molar mass near 450—for example, cloxacillin has a molar mass of 436 g/mol. The key structural feature of the penicillins is the four-membered β-lactam ring; this structural moiety is essential for penicillin's antibacterial activity. The β-lactam ring is itself fused to a five-membered thiazolidine ring. The fusion of these two rings causes the β-lactam ring to be more reactive than monocyclic β-lactams because the two fused rings distort the β-lactam amide bond and therefore remove the resonance stabilisation normally found in these chemical bonds.[20]

History

Discovery

Alexander Fleming
Alexander Fleming, who is credited with discovering penicillin in 1928.
Sample of penicillin mould presented by Alexander Fleming to Douglas Macleod, 1935 (9672239344)
Sample of penicillium mould presented by Alexander Fleming to Douglas Macleod, 1935

Starting in the late 19th century there had been many accounts by scientists and physicians on the antibacterial properties of the different types of moulds including the mould penicillium but they were unable to discern what process was causing the effect.[21] The effects of penicillium mould would finally be isolated in 1928 by Scottish scientist Alexander Fleming, in work that seems to have been independent of those earlier observations.[22] Fleming recounted that the date of his discovery of penicillin was on the morning of Friday 28 September 1928.[23] The traditional version of this story describes the discovery as a serendipitous 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 Staphylococci that had been mistakenly left open was contaminated by blue-green mould from an open window, which formed a visible growth.[24] There was a halo of inhibited bacterial growth around the mould. Fleming concluded that the mould released a substance that repressed the growth and caused lysing of the bacteria.[25]

Once Fleming made his discovery he grew a pure culture and discovered it was a Penicillium mould, now known as Penicillium chrysogenum. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould. Fleming asked C. J. La Touche to help identify the mould, which he incorrectly identified as Penicillium rubrum (later corrected by Charles Thom). He expressed initial optimism that penicillin would be a useful disinfectant, because of its high potency and minimal toxicity in comparison to antiseptics of the day, and noted its laboratory value in the isolation of Bacillus influenzae (now called Haemophilus influenzae).[24][26]

Fleming was a famously poor communicator and orator, which meant his findings were not initially given much attention.[24] He was unable to convince a chemist to help him extract and stabilize the antibacterial compound found in the broth filtrate. Despite this, he remained interested in the potential use of penicillin and presented a paper entitled "A Medium for the Isolation of Pfeiffer's Bacillus" to the Medical Research Club of London, which was met with little interest and even less enthusiasm by his peers. Had Fleming been more successful at making other scientists interested in his work, penicillin for medicinal use would possibly have been developed years earlier.[24]

Despite the lack of interest of his fellow scientists, he did conduct several experiments on the antibiotic substance he discovered. The most important result proved it was nontoxic in humans by first performing toxicity tests in animals and then on humans. His subsequent experiments on penicillin's response to heat and pH allowed Fleming to increase the stability of the compound.[26] The one test that modern scientists would find missing from his work was the test of penicillin on an infected animal, the results of which would likely have sparked great interest in penicillin and sped its development by almost a decade.[24] The importance of his work has been recognized by the placement of an International Historic Chemical Landmark at the Alexander Fleming Laboratory Museum in London on November 19, 1999.[27]

Medical application

Howard Walter Florey 1945
Florey (pictured), Fleming and Chain shared a Nobel Prize in 1945 for their work on penicillin.

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. 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, and failed to cure a fifth.[28][29][30]

In 1939, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain, Edward Abraham, Arthur Duncan Gardner, Norman Heatley, Margaret Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made progress in showing the in vivo bactericidal action of penicillin.[31][32] In 1940, they showed that penicillin effectively cured bacterial infection in mice.[33][34] In 1941, they treated a policeman, Albert Alexander, with a severe face infection; his condition improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully.[35] In December 1942, survivors of the Cocoanut Grove fire in Boston were the first burn patients to be successfully treated with penicillin.[36]

Mass production

Penicillin Past, Present and Future- the Development and Production of Penicillin, England, 1943 D16959
A technician preparing penicillin in 1943

By late 1940, the Oxford team under Howard Florey had devised a method of mass-producing the drug, but yields remained low.[35] In 1941, Florey and Heatley travelled to the US in order to interest pharmaceutical companies in producing the drug and inform them about their process.[35]

Florey and Chain shared the 1945 Nobel Prize in Medicine with Fleming for their work.

The challenge of mass-producing this drug was daunting. On March 14, 1942, the first patient was treated for streptococcal septicemia with US-made penicillin produced by Merck & Co.[37] Half of the total supply produced at the time was used on that one patient. By June 1942, just enough US penicillin was available to treat ten patients.[38] In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe.[39] 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. After a worldwide search in 1943, a mouldy cantaloupe in a Peoria, Illinois market was found to contain the best strain of mould for production using the corn steep liquor process.[40] Pfizer scientist Jasper H. Kane suggested using a deep-tank fermentation method for producing large quantities of pharmaceutical-grade penicillin.[41][42] Large-scale production resulted from the development of a deep-tank fermentation plant by chemical engineer Margaret Hutchinson Rousseau.[43] As a direct result of the war and the War Production Board, by June 1945, over 646 billion units per year were being produced.[39]

PenicillinPSAedit
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.[44] 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. 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. Methods for mass production of penicillin were patented by Andrew Jackson Moyer in 1945.[45][46][47] Florey had not patented penicillin, having been advised by Sir Henry Dale that doing so would be unethical.[35]

Penicillin is actively excreted, and about 80% of a penicillin dose is cleared from the body within three to four hours of administration. 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.[48] This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion. 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. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are administered together, probenecid competitively inhibits the excretion of penicillin, increasing penicillin's concentration and prolonging its activity. Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined.[48] Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins.[11]

After World War II, Australia was the first country to make the drug available for civilian use. In the U.S., penicillin was made available to the general public on March 15, 1945.[49]

Dorothy Hodgkin Nobel
Dorothy Hodgkin determined the chemical structure of penicillin.

Structure determination and total synthesis

Molecular model of Penicillin by Dorothy Hodgkin (9663803982)
Dorothy Hodgkin's model of penicillin's structure.

The chemical structure of penicillin was first proposed by Edward Abraham in 1942[31] and was later confirmed in 1945 using X-ray crystallography by Dorothy Crowfoot Hodgkin, who was also working at Oxford.[50] She later received the Nobel prize for this and other structure determinations.

Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957.[51][52][53] Sheehan had started his studies into penicillin synthesis in 1948, and during these investigations developed new methods for the synthesis of peptides, as well as new protecting groups—groups that mask the reactivity of certain functional groups.[53][54] Although the initial synthesis developed by Sheehan was not appropriate for mass production of penicillins, one of the intermediate compounds in Sheehan's synthesis was 6-aminopenicillanic acid (6-APA), the nucleus of penicillin.[53][55][56] Attaching different groups to the 6-APA 'nucleus' of penicillin allowed the creation of new forms of penicillin.

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 isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance).

The first major development was ampicillin in 1961. It offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the methicillin-resistant Staphylococcus aureus (MRSA) strains that subsequently emerged.[57]

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. However, the usefulness of the β-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.[58]

Production

Penicillin bioreactor
A 1957 fermentor (bioreactor) used to grow Penicillium mould.

Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin.

α-ketoglutarate + AcCoAhomocitrateL-α-aminoadipic acidL-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.

The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress, which is required for induction of penicillin production. The available carbon sources are also important: glucose inhibits penicillin production, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must also be carefully controlled.

The biotechnological method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These techniques include error-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR.

Semisynthetic penicillins are prepared starting from the penicillin nucleus 6-APA.

Biosynthesis

Penicillin-biosynthesis
Penicillin G biosynthesis

Overall, there are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin).

  • The first step is the condensation of three amino acids—L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide.[59][60][61] Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine.[62][63] The condensed tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine (ACV). The condensation reaction and epimerization are both catalyzed by the enzyme δ-(L-α-aminoadipyl)-L-cysteine-D-valine synthetase (ACVS), a nonribosomal peptide synthetase or NRPS.
  • The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC.[59][60] Isopenicillin N is a very weak intermediate, because it does not show strong antibiotic activity.[62]
  • The final step is a transamidation by isopenicillin N N-acyltransferase, in which the α-aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins.[59]

See also

References

  1. ^ Walling AD (September 15, 2006). "Tips from Other Journals – Antibiotic Use During Pregnancy and Lactation". American Family Physician. 74 (6): 1035. Retrieved September 25, 2015.
  2. ^ a b Gonzalez-Estrada A, Radojicic C (May 2015). "Penicillin allergy: A practical guide for clinicians". Cleveland Clinic Journal of Medicine. 82 (5): 295–300. doi:10.3949/ccjm.82a.14111. PMID 25973877.
  3. ^ "Discovery and Development of Penicillin". American Chemical Society. Retrieved 30 August 2015.
  4. ^ Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford. 2009. p. 56. ISBN 978-0-19-103962-1.
  5. ^ "penicillin" – via The Free Dictionary.
  6. ^ Garrod LP (February 1960). "Relative antibacterial activity of three penicillins". British Medical Journal. 1 (5172): 527–9. doi:10.1136/bmj.1.5172.527. PMC 1966560. PMID 13826674.
  7. ^ Garrod LP (December 1960). "The relative antibacterial activity of four penicillins". British Medical Journal. 2 (5214): 1695–6. doi:10.1136/bmj.2.5214.1695. PMC 2098302. PMID 13703756.
  8. ^ "Penicillin G and Penicillin V". livertox.nih.gov. Retrieved 2016-09-25.
  9. ^ "Penicillin (Benzylpenicillin, Penicillin G, Bicillin C-R/L-A, Pfizerpen, Wycellin)". The Antimicrobial Index. Knowledgebase. Retrieved 4 March 2014.
  10. ^ "Penicillin G sodium salt Susceptibilty and Resistance Data" (PDF). TOKU-E. Retrieved 4 March 2014.
  11. ^ a b c Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 978-0-9757919-2-9.
  12. ^ a b Hitchings A, Lonsdale D, Burrage D, Baker E (2015). Top 100 drugs : clinical pharmacology and practical prescribing. pp. 174–181. ISBN 978-0-7020-5516-4.
  13. ^ Yocum RR, Rasmussen JR, Strominger JL (May 1980). "The mechanism of action of penicillin. Penicillin acylates the active site of Bacillus stearothermophilus D-alanine carboxypeptidase". The Journal of Biological Chemistry. 255 (9): 3977–86. PMID 7372662.
  14. ^ "Benzylpenicillin". www.drugbank.ca. Retrieved 22 January 2019.
  15. ^ Van Bambeke F, Lambert D, Mingeot-Leclercq M, Tulkens P (1999). Mechanism of Action (PDF).
  16. ^ Winstanley TG, Hastings JG (February 1989). "Penicillin-aminoglycoside synergy and post-antibiotic effect for enterococci". The Journal of Antimicrobial Chemotherapy. 23 (2): 189–99. doi:10.1093/jac/23.2.189. PMID 2708179.
  17. ^ Kasten B, Reski R (March 30, 1997). "β-lactam antibiotics inhibit chloroplast division in a moss (Physcomitrella patens) but not in tomato (Lycopersicon esculentum)". Journal of Plant Physiology. 150 (1–2): 137–140. doi:10.1016/S0176-1617(97)80193-9.
  18. ^ Mucsi Z, Chass GA, Ábrányi-Balogh P, Jójárt B, Fang DC, Ramirez-Cuesta AJ, Viskolcz B, Csizmadia IG (December 2013). "Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory". Physical Chemistry Chemical Physics. 15 (47): 20447–55. Bibcode:2013PCCP...1520447M. doi:10.1039/c3cp50868d. PMID 23760063.
  19. ^ Levison ME, Levison JH (December 2009). "Pharmacokinetics and pharmacodynamics of antibacterial agents". Infectious Disease Clinics of North America. 23 (4): 791–815, vii. doi:10.1016/j.idc.2009.06.008. PMC 3675903. PMID 19909885.
  20. ^ Nicolaou (1996), pg. 43.
  21. ^ Thomas J. Dougherty, Michael J. Pucci, Antibiotic Discovery and Development, Springer Science & Business Media – 2011, pages 79–80
  22. ^ Ralph Landau, Basil Achilladelis, Alexander Scriabine, Pharmaceutical Innovation: Revolutionizing Human Health, Chemical Heritage Foundation – 1999, page 162
  23. ^ Haven KF (1994). Marvels of Science : 50 Fascinating 5-Minute Reads. Littleton, CO: Libraries Unlimited. p. 182. ISBN 978-1-56308-159-0.
  24. ^ a b c d e Lax E (2004). The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle. Holt Paperbacks. ISBN 978-0-8050-7778-0.
  25. ^ Bud R (2009). Penicillin: Triumph and Tragedy. Oxford University Press. ISBN 978-0-19-954161-4.
  26. ^ a b Krylov AK (1929). "[Gastroenterologic aspects of the clinical picture of internal diseases]". Terapevticheskii Arkhiv. 63 (2): 139–41. PMC 2048009. PMID 2048009. Reprinted in Fleming A (2001). "On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. 1929". Bulletin of the World Health Organization. 79 (8): 780–90. PMC 2566493. PMID 11545337.
  27. ^ "Discovery and Development of Penicillin". International Historic Chemical Landmarks. American Chemical Society. Retrieved August 21, 2018.
  28. ^ Wainwright M, Swan HT (January 1986). "C.G. Paine and the earliest surviving clinical records of penicillin therapy". Medical History. 30 (1): 42–56. doi:10.1017/S0025727300045026. PMC 1139580. PMID 3511336.
  29. ^ Howie J (July 1986). "Penicillin: 1929-40". British Medical Journal. 293 (6540): 158–9. doi:10.1136/bmj.293.6540.158. PMC 1340901. PMID 3089435.
  30. ^ Wainwright M (January 1987). "The history of the therapeutic use of crude penicillin". Medical History. 31 (1): 41–50. doi:10.1017/s0025727300046305. PMC 1139683. PMID 3543562.
  31. ^ a b Jones DS, Jones JH (2014-12-01). "Sir Edward Penley Abraham CBE. 10 June 1913 – 9 May 1999". Biographical Memoirs of Fellows of the Royal Society. 60: 5–22. doi:10.1098/rsbm.2014.0002. ISSN 0080-4606.
  32. ^ "Ernst B. Chain – Nobel Lecture: The Chemical Structure of the Penicillins". www.nobelprize.org. Retrieved 2017-05-10.
  33. ^ Clark R (1985). The Life of Ernst Chain: Penicillin and Beyond.
  34. ^ "Animal Experiments: Further Views". The New York Times. 1992-05-24. Retrieved 2014-10-11.
  35. ^ a b c d "Making Penicillin Possible: Norman Heatley Remembers". ScienceWatch. Thomson Scientific. 2007. Archived from the original on February 21, 2007. Retrieved 2007-02-13.
  36. ^ Levy SB (2002). The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. Da Capo Press. pp. 5–7. ISBN 978-0-7382-0440-6.
  37. ^ Grossman CM (July 2008). "The first use of penicillin in the United States". Annals of Internal Medicine. 149 (2): 135–6. doi:10.7326/0003-4819-149-2-200807150-00009. PMID 18626052.
  38. ^ Mailer JS, Mason B. "Penicillin : Medicine's Wartime Wonder Drug and Its Production at Peoria, Illinois". lib.niu.edu. Retrieved February 11, 2008.
  39. ^ a b Parascandola J (1980). The History of antibiotics: a symposium. American Institute of the History of Pharmacy No. 5. ISBN 978-0-931292-08-8.
  40. ^ Bellis M. "The History of Penicillin". Inventors. About.com. Retrieved October 30, 2007.
  41. ^ Lehrer S (2006). Explorers of the Body: Dramatic Breakthroughs in Medicine from Ancient Times to Modern Science (2nd ed.). New York: iUniverse. pp. 329–330. ISBN 978-0-595-40731-6.
  42. ^ Greenwood D (2008). Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. Oxford: Oxford University Press. p. 109. ISBN 978-0-19-953484-5.
  43. ^ Madhavan G (Aug 20, 2015). Think Like an Engineer. Oneworld Publications. pp. 83–85, 91–93. ISBN 978-1-78074-637-1. Retrieved 20 November 2016.
  44. ^ "ExplorePAhistory.com". Retrieved May 11, 2009.
  45. ^ Andrew Jackson Moyer, Method for Production of Penicillin, United States Patent Office, US Patent 2,442,141, filed 11 May 1945, issued 25 March 1948.
  46. ^ Andrew Jackson Moyer, Method for Production of Penicillin, United States Patent Office, US Patent 2,443,989, filed 11 May 1945, issued 22 June 1948.
  47. ^ Andrew Jackson Moyer, Method for Production of Penicillin, United States Patent Office, US Patent 2,476,107, filed 11 May 1945, issued 12 July 1949.
  48. ^ a b Silverthorn DU (2004). Human physiology: an integrated approach (3rd ed.). Upper Saddle River (NJ): Pearson Education. ISBN 978-0-8053-5957-2.
  49. ^ "Discovery and development of penicillin". American Chemical Society. 1999.
  50. ^ The Nobel Prize in Chemistry 1964, Perspectives. Retrieved July 14, 2012.
  51. ^ Sheehan JC, H enery-Logan KR (March 5, 1957). "The Total Synthesis of Penicillin V". Journal of the American Chemical Society. 79 (5): 1262–1263. doi:10.1021/ja01562a063.
  52. ^ Sheehan JC, Henery-Loganm KR (June 20, 1959). "The Total Synthesis of Penicillin V". Journal of the American Chemical Society. 81 (12): 3089–3094. doi:10.1021/ja01521a044.
  53. ^ a b c Corey EJ, Roberts JD. "Biographical Memoirs: John Clark Sheehan". The National Academy Press. Retrieved January 28, 2013.
  54. ^ Nicolaou KC, Vourloumis D, Winssinger N, Baran PS (January 2000). "The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century". Angewandte Chemie. 39 (1): 44–122. doi:10.1002/(SICI)1521-3773(20000103)39:1<44::AID-ANIE44>3.0.CO;2-L. PMID 10649349.
  55. ^ "Professor John C. Sheehan Dies at 76". MIT News. April 1, 1992. Retrieved January 28, 2013.
  56. ^ Sheehan JC (1982). The Enchanted Ring: The Untold Story of Penicillin. MIT Press. ISBN 978-0-262-19204-0.
  57. ^ Colley EW, Mcnicol MW, Bracken PM (March 1965). "Methicillin-Resistant Staphylococci in a General Hospital". Lancet. 1 (7385): 595–7. doi:10.1016/S0140-6736(65)91165-7. PMID 14250094.
  58. ^ James CW, Gurk-Turner C (January 2001). "Cross-reactivity of beta-lactam antibiotics". Proceedings. 14 (1): 106–7. PMC 1291320. PMID 16369597.
  59. ^ a b c Al-Abdallah Q, Brakhage AA, Gehrke A, Plattner H, Sprote P, Tuncher A (2004). "Regulation of Penicillin Biosynthesis in Filamentous Fungi". In Brakhage AA. Molecular Biotechnology of Fungal beta-Lactam Antibiotics and Related Peptide Synthetases. Advances in Biochemical Engineering/Biotechnology. 88. pp. 45–90. doi:10.1007/b99257. ISBN 978-3-540-22032-9.
  60. ^ a b Brakhage AA (September 1998). "Molecular regulation of beta-lactam biosynthesis in filamentous fungi". Microbiology and Molecular Biology Reviews. 62 (3): 547–85. PMC 98925. PMID 9729600.
  61. ^ Schofield CJ, Baldwin JE, Byford MF, Clifton I, Hajdu J, Hensgens C, Roach P (December 1997). "Proteins of the penicillin biosynthesis pathway". Current Opinion in Structural Biology. 7 (6): 857–64. doi:10.1016/s0959-440x(97)80158-3. PMID 9434907.
  62. ^ a b Martín JF, Gutiérrez S, Fernández FJ, Velasco J, Fierro F, Marcos AT, Kosalkova K (September 1994). "Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins". Antonie van Leeuwenhoek. 65 (3): 227–43. doi:10.1007/BF00871951. PMID 7847890.
  63. ^ Baker, W. L., Lonergan, G. T. "Chemistry of Some Fluorescamine-Amine Derivatives with Relevance to the Biosynthesis of Benzylpenicillin by Fermentation". J Chem Technol Biot. 2002, 77, pp1283-1288.

Further reading

  • Nicolaou KC, Corey EJ (1996). Classics in Total Synthesis : Targets, Strategies, Methods (5. repr. ed.). Weinheim: VCH. ISBN 978-3-527-29284-4.
  • Dürckheimer W, Blumbach J, Lattrell R, Scheunemann KH (March 1, 1985). "Recent Developments in the Field of β-Lactam Antibiotics". Angewandte Chemie International Edition in English. 24 (3): 180–202. doi:10.1002/anie.198501801.
  • Hamed RB, Gomez-Castellanos JR, Henry L, Ducho C, McDonough MA, Schofield CJ (January 2013). "The enzymes of β-lactam biosynthesis". Natural Product Reports. 30 (1): 21–107. doi:10.1039/c2np20065a. PMID 23135477.

External links

Alexander Fleming

Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician, microbiologist, and pharmacologist. His best-known discoveries are the enzyme lysozyme in 1923 and the world's first antibiotic substance benzylpenicillin (Penicillin G) from the mould Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain. He wrote many articles on bacteriology, immunology, and chemotherapy.

Fleming was knighted for his scientific achievements in 1944. In 1999, he was named in Time magazine's list of the 100 Most Important People of the 20th century. In 2002, he was chosen in the BBC's television poll for determining the 100 Greatest Britons, and in 2009, he was also voted third "greatest Scot" in an opinion poll conducted by STV, behind only Robert Burns and William Wallace.

Antibiotic

An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.

Sometimes, the term antibiotic which means "opposing life", based on Greek roots, (ἀντι-) anti: "against" and (βίος-) biotic: "life", is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas nonantibiotic antibacterials (such as sulfonamides and antiseptics) are fully synthetic. However, both classes have the same goal of killing or preventing the growth of microorganisms, and both are included in antimicrobial chemotherapy. "Antibacterials" include antiseptic drugs, antibacterial soaps, and chemical disinfectants, whereas antibiotics are an important class of antibacterials used more specifically in medicine and sometimes in livestock feed.

There's evidence of antibiotic use since ancient times. Many civilizations used topical application of mouldy bread, with many references to its beneficial effects arising from ancient Egypt, China, Serbia, Greece and Rome. The first person to directly document the use of moulds to treat infections was John Parkinson (1567–1650). Antibiotics truly revolutionized medicine in the 20th century. Alexander Fleming (1881–1955) discovered modern day penicillin in 1928. After realizing the great potential there was in penicillin, Fleming pursued the challenge of how to market it and translate it to commercial use. With help from other biochemists, penicillin was finally available for widespread use. This was significantly beneficial during wartime. Unfortunately, it didn't take long for resistance to begin. Effectiveness and easy access have also led to their overuse and some bacteria have developed resistance. This has led to widespread problems, and the World Health Organization have classified antimicrobial resistance as a "serious threat [that] is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country".

Benzathine benzylpenicillin

Benzathine benzylpenicillin, also known as benzathine penicillin G, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is to treat strep throat, diphtheria, syphilis, and yaws. It is also used to prevent rheumatic fever. It is given by injection into a muscle.Side effects include allergic reactions including anaphylaxis, and pain at the site of injection. When used to treat syphilis a reaction known as Jarisch-Herxheimer may occur. It is not recommended in those with a history of penicillin allergy or those with syphilis involving the nervous system. Use during pregnancy is generally safe. It is in the penicillin and beta lactam class of medications and works via benzylpenicillin. The benzathine component slowly releases the penicillin making the combination long acting.Benzathine benzylpenicillin was patented in 1950. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about 0.27 to 1.71 USD for a course of treatment. In the United States the medication costs 50 to 100 USD for a dose as of 2015. In the United Kingdom it costs the NHS about 0.95 to 1.89 pounds a dose as of 2015.

Benzylpenicillin

Benzylpenicillin, also known as penicillin G, is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis, diphtheria, gas gangrene, leptospirosis, cellulitis, and tetanus. It is not a first-line agent for pneumococcal meningitis. Benzylpenicillin is given by injection into a vein or muscle. Two long-acting forms benzathine benzylpenicillin and procaine benzylpenicillin are available for use by injection into a muscle.Side effects include diarrhea, seizures, and allergic reactions including anaphylaxis. When used to treat syphilis a reaction known as Jarisch–Herxheimer may occur. It is not recommended in those with a history of penicillin allergy. Use during pregnancy is generally safe. It is in the penicillin and β-lactam class of medications.Benzylpenicillin was discovered in 1929 by Alexander Fleming and came into commercial use in 1942. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.24–2.72 per day. In the United States a course of treatment costs $100–200.

Cefalexin

Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a beta-lactam antibiotic within the class of first-generation cephalosporins. It works similarly to other agents within this class, including intravenous cefazolin, but can be taken by mouth.Cefalexin can treat certain bacterial infections, including those of the middle ear, bone and joint, skin, and urinary tract. It may also be used for certain types of pneumonia, strep throat, and to prevent bacterial endocarditis. Cefalexin is not effective against infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus, or Pseudomonas. Like other antibiotics, cefalexin cannot treat viral infections, such as the flu, common cold or acute bronchitis. Cefalexin can be used in those who have mild or moderate allergies to penicillin. However, it is not recommended in those with severe penicillin allergies.Common side effects include stomach upset and diarrhea. Allergic reactions or infections with Clostridium difficile, a cause of diarrhea, are also possible. Use during pregnancy or breast feeding does not appear to be harmful to the baby. It can be used in children and those over 65 years of age. Those with kidney problems may require a decrease in dose.In 2012, cefalexin was one of the top 100 most prescribed medications in the United States. In Canada, it was the 5th most common antibiotic used in 2013. In Australia, it is one of the top 15 most prescribed medications. Cefalexin was developed in 1967. It was first marketed in 1969 and 1970 under the names Keflex and Ceporex, among others. Generic drug versions are available under several other trade names and are inexpensive. Cefalexin is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.

Chicken soup

Chicken soup is a soup made from chicken, simmered in water, usually with various other ingredients. The classic chicken soup consists of a clear chicken broth, often with pieces of chicken or vegetables; common additions are pasta, noodles, dumplings, or grains such as rice and barley. Chicken soup has acquired the reputation of a folk remedy for colds and influenza, and in many countries is considered a comfort food.

DD-transpeptidase

DD-transpeptidase (EC 3.4.16.4, DD-peptidase, DD-transpeptidase, DD-carboxypeptidase, D-alanyl-D-alanine carboxypeptidase, D-alanyl-D-alanine-cleaving-peptidase, D-alanine carboxypeptidase, D-alanyl carboxypeptidase, and serine-type D-Ala-D-Ala carboxypeptidase.) is a bacterial enzyme that catalyzes the transfer of the R-L-aca-D-alanyl moiety of R-L-aca-D-alanyl-D-alanine carbonyl donors to the γ-OH of their active-site serine and from this to a final acceptor. It is involved in bacterial cell wall biosynthesis, namely, the transpeptidation that crosslinks the peptide side chains of peptidoglycan strands.The antibiotic penicillin irreversibly binds to and inhibits the activity of the transpeptidase enzyme by forming a highly stable penicilloyl-enzyme intermediate. Because of the interaction between penicillin and transpeptidase, this enzyme is also known as penicillin-binding protein (PBP).

Extended-spectrum penicillin

The extended-spectrum penicillins are a group of antibiotics that have the widest antibacterial spectrum of all penicillins. Some sources identify them with antipseudomonal penicillins, others consider these types to be distinct. This group includes the carboxypenicillins and the ureidopenicillins. Aminopenicillins, in contrast, do not have activity against Pseudomonas species, as their positively charged amino group does not hinder degradation by bacterially produced beta-lactamases.

Flucloxacillin

Flucloxacillin (INN) or floxacillin (USAN) is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus aureus as it is beta-lactamase stable. However, it is ineffective against methicillin-resistant Staphylococcus aureus (MRSA). It is very similar to dicloxacillin; they are considered interchangeable. Flucloxacillin is supplied under a variety of trade names including Floxapen (Beecham, now GSK), Flopen (CSL), Staphylex (Alphapharm), Softapen (Rephco Pharmaceuticals Limited), Flubex (Beximco Pharmaceuticals Ltd, Bangladesh), and Flupen (for state use only in South Africa). It is no longer available in the United States.

Glucose oxidase

The glucose oxidase enzyme (GOx) also known as notatin (EC number 1.1.3.4) is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and insects and displays antibacterial activity when oxygen and glucose are present.

Glucose oxidase is widely used for the determination of free glucose in body fluids (diagnostics), in vegetal raw material, and in the food industry. It also has many applications in biotechnologies, typically enzyme assays for biochemistry including biosensors in nanotechnologies. It was first isolated by Detlev Müller in 1928 from Aspergillus niger.

History of penicillin

The history of penicillin follows a number of observations and discoveries of apparent evidence of antibiotic activity in molds before the modern isolation of the chemical penicillin in 1928. There are anecdotes about ancient societies using molds to treat infections, and in the following centuries many people observed the inhibition of bacterial growth by various molds. However, it is unknown if the species involved were Penicillium species or if the antimicrobial substances produced were penicillin.

The Scottish physician Alexander Fleming was the first to suggest that a Penicillium mold must secrete an antibacterial substance, and the first to concentrate the active substance involved, which he named penicillin, in 1928. Penicillin was the first modern antibiotic. During the next twelve years Fleming grew, distributed, and studied the original mold, which was determined to be a rare variant of Penicillium notatum (now Penicillium chrysogenum).Many later scientists were involved in the stabilization and mass production of penicillin and in the search for more productive strains of Penicillium. Important contributors include Ernst Chain, Howard Florey, Norman Heatley, and Edward Abraham. Shortly after the discovery of penicillin, scientists found that some disease-causing pathogens display antibiotic resistance to penicillin. Research that aims to develop more effective strains and to study the causes and mechanisms of antibiotic resistance continues today.

Howard Florey

Howard Walter Florey, Baron Florey, (24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Sir Ernst Chain and Sir Alexander Fleming for his role in the development of penicillin.

Although Fleming received most of the credit for the discovery of penicillin, it was Florey who carried out the first ever clinical trials in 1941 of penicillin at the Radcliffe Infirmary in Oxford on the first patient, a constable from Oxford. The patient started to recover but subsequently died because Florey was unable, at that time, to make enough penicillin. It was Florey and Chain who actually made a useful and effective drug out of penicillin, after the task had been abandoned as too difficult.

Florey's discoveries, along with the discoveries of Alexander Fleming and Ernst Chain, are estimated to have saved over 200 million lives, and he is consequently regarded by the Australian scientific and medical community as one of its greatest figures. Sir Robert Menzies, Australia's longest-serving Prime Minister, said, "In terms of world well-being, Florey was the most important man ever born in Australia".

Pathogenic bacteria

Pathogenic bacteria are bacteria that can cause disease. This article deals with human pathogenic bacteria. Although most bacteria are harmless or often beneficial, some are pathogenic, with the number of species estimated as fewer than a hundred that are seen to cause infectious diseases in humans. By contrast, several thousand species exist in the human digestive system.

One of the bacterial diseases with the highest disease burden is tuberculosis, caused by Mycobacterium tuberculosis bacteria, which kills about 2 million people a year, mostly in sub-Saharan Africa. Pathogenic bacteria contribute to other globally important diseases, such as pneumonia, which can be caused by bacteria such as Streptococcus and Pseudomonas, and foodborne illnesses, which can be caused by bacteria such as Shigella, Campylobacter, and Salmonella. Pathogenic bacteria also cause infections such as tetanus, typhoid fever, diphtheria, syphilis, and leprosy. Pathogenic bacteria are also the cause of high infant mortality rates in developing countries.Koch's postulates are the standard to establish a causative relationship between a microbe and a disease.

Penicillin binding proteins

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics (except for tabtoxinine-β-lactam, which inhibits glutamine synthetase) bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases. Specifically, PBPs are DD-transpeptidases.

Phenoxymethylpenicillin

Phenoxymethylpenicillin, also known as penicillin V and penicillin VK, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for the treatment of strep throat, otitis media, and cellulitis. It is also used to prevent rheumatic fever and to prevent infections following removal of the spleen. It is given by mouth.Side effects include diarrhea, nausea, and allergic reactions including anaphylaxis. It is not recommended in those with a history of penicillin allergy. It is relatively safe for use during pregnancy. It is in the penicillin and beta lactam family of medications. It usually results in bacterial death.Phenoxymethylpenicillin was first made in 1948. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is about US$0.05–0.96 per day. In the United States a course of treatment costs less than $25.

Procaine benzylpenicillin

Procaine benzylpenicillin also known as penicillin G procaine, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for syphilis, anthrax, mouth infections, pneumonia, diphtheria, cellulitis, and animal bites. It is given by injection into a muscle.Side effects include pain at the site of injection, blood clotting problems, seizures, and allergic reactions including anaphylaxis. When used to treat syphilis a reaction known as Jarisch-Herxheimer may occur. It is not recommended in those with a history of penicillin allergy or procaine allergy. Use during pregnancy and breastfeeding is relatively safe. Procaine benzylpenicillin is in the penicillin and beta lactam family of medications. It works via benzylpenicillin and results in bacterial death. Procaine makes the combination long acting.Procaine benzylpenicillin was introduced for medical use in 1948. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.09–0.18 per day. In the United States a course of treatment costs $100–200.

Side effects of penicillin

The side effects of penicillin are bodily responses to penicillin and closely related antibiotics that do not relate directly to its effect on bacteria. A side effect is an effect that is not intended with normal dosaging. Some of these reactions are visible and some occur in the body's organs or blood. Penicillins are a widely used group of medications that are effective for the treatment of a wide variety of bacterial infections in human adults and children as well as other species. Some side effects are predictable, of which some are common but not serious, some are uncommon and serious and others are rare. The route of administration of penicillin can have an effect on the development of side effects. An example of this is irritation and inflammation that develops at a peripheral infusion site when penicillin is administered intravenously. In addition, penicillin is available in different forms. There are different penicillin medications (penicillin G benzathine, penicillin G potassium, Penicillin G sodium, penicillin G procaine, and penicillin V) as well as a number of β-lactam antibiotics derived from penicillin (e.g. amoxicillin) generally also referred to as "penicillin".

Side effects may only last for a short time and then go away. Side effects can be relieved in some cases with non pharmacological treatment. Some side effects require treatment to correct potentially serious and sometimes fatal reactions to penicillin. Penicillin has not been found to cause birth defects.

Tonsillitis

Tonsillitis is inflammation of the tonsils, typically of rapid onset. It is a type of pharyngitis. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and large lymph nodes around the neck. Complications include peritonsillar abscess.Tonsillitis is most commonly caused by a viral infection, with about 5% to 40% of cases caused by a bacterial infection. When caused by the bacterium group A streptococcus, it is referred to as strep throat. Rarely bacteria such as Neisseria gonorrhoeae, Corynebacterium diphtheriae, or Haemophilus influenzae may be the cause. Typically the infection is spread between people through the air. A scoring system, such as the Centor score, may help separate possible causes. Confirmation may be by a throat swab or rapid strep test.Treatment efforts involve improving symptoms and decreasing complications. Paracetamol (acetaminophen) and ibuprofen may be used to help with pain. If strep throat is present the antibiotic penicillin by mouth is generally recommended. In those who are allergic to penicillin, cephalosporins or macrolides may be used. In children with frequent episodes of tonsillitis, tonsillectomy modestly decreases the risk of future episodes.About 7.5% of people have a sore throat in any three-month period and 2% of people visit a doctor for tonsillitis each year. It is most common in school aged children and typically occurs in the fall and winter months. The majority of people recover with or without medication. In 40% of people, symptoms resolve within three days, and in 80% symptoms resolve within one week, regardless of if streptococcus is present. Antibiotics decrease symptom duration by approximately 16 hours.

Β-lactam antibiotic

β-lactam antibiotics (beta-lactam antibiotics) are a class of antibiotic consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds.Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.

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