Penicillin Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived [1] from Penicillium fungi.

They include penicillin G,procaine penicillin, benzathine penicillin, and penicillin V. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases, such as syphilis, and infections caused by staphylococci and streptococci. Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are β-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.

Medical uses
The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), andphenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer period. Phenoxymethylpenicillin is less active against Gram-negative bacteria than [2][3] benzylpenicillin. Benzylpenicillin, procaine penicillin and benzathine penicillin are given by injection (parenterally), but phenoxymethylpenicillin is given orally.

Adverse effects
Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection(including candidiasis). Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in epileptics), andpseudomembranous [4] colitis.

which further digest the bacteria's existing peptidoglycan. β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links in the bacterial cell wall. even in the absence of cell division. simultaneously building and breaking down portions of the cell wall as they grow and divide. the antibiotic causes cytolysis or death due to osmotic pressure). The enzymes that hydrolyze the peptidoglycan cross-links continue to function. the relatively small size of the penicillin molecule allows it to penetrate deeply into the cell wall. the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins. In addition.Mechanism of Action Bacteria that attempt to divide in the presence of penicillin fail to do so and end up shedding their cell walls in the process. This imbalance between cell wall production and degradation is responsible for the rapid cell-killing action of this class of drugs. This is in contrast to the other major class of anitbiotics that inhibit cell wall synthesis. In addition. Bacteria constantly remodel their peptidoglycan cell walls. the glycopeptide antibiotics (which includes vancomycin and teicoplanin). but have no direct effect on cell wall degradation. The β-lactam moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the peptidoglycan molecules in bacteria. . affecting its entire depth. which weakens the cell wall of the bacterium (in other words.

which he dubbed penicillin. Normal penicillin has a molecular weight of 313 to 334 g/mol (latter for penicillin G). since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily. like other β-lactam antibiotics. cloxacillin has a molar mass of 476 g/mol and dicloxacillin has a molar mass of 492 g/mol. The term "penam" is used to describe the core skeleton of a member of the penicillin antibiotics. Penicillins. and the division of chloroplasts of bryophytes. He showed that. Production is also limited by feedback in the synthesis pathway of penicillin. fig 1680. they have no effect on the plastids of the highly developed vascular plants. This skeleton has the molecular formula R-C9H11N2O4S. several others reported the bacteriostatic effects of Penicillium earlier than Fleming. It is not produced during active growth. Penicillin types with additional molecular groups attached may have a molar mass around 500 g/mol. but also the division of cyanelles. This results in a lowered MBC for susceptible organisms. However. if Penicillium notatum were grown in the appropriate substrate. including cyanobacteria. [6] [7][8] Production Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. Professor of Botany and Zoology of the Faculty of Medicine of Rio de Janeiro. he stated: O bolor (Penicillium infestans. Penicillium glaucum. The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey. Ascophora e tantos outros) é util porque nutre-se decompondo e destruindo as materias organicas em putrefacção. This supports the endosymbiotic theory of the evolution of plastid division in [5] land plants. "Elements of General and Medical Botany" (under a section titled 'Useful fungi. e de . harmful and curious'). Brazil. Joaquim Monteiro Caminhoá. Gram-negative bacteria do [citation needed] not lose their cell walls completely and are called spheroplasts after treatment with penicillin. In his book. thephotosynthetic organelles of the glaucophytes.Gram-positive bacteria are called protoplasts when they lose their cell walls. where R is a variable side chain. by John [16] Tyndall. allowing their disruption of bacterial protein synthesis within the cell. block not only the division of bacteria. This serendipitous observation began the modern era of antibiotic discovery. The use of bread with a blue mould (presumed to be Penicillium) as a means of treating suppurating [citation needed] wounds was a staple of folk medicine in Europe since the Middle Ages. The first published reference appears in the publication of the Royal Society in 1875. In contrast. it would exude a substance with antibiotic properties. Penicillin shows a synergistic effect with aminoglycosides. For [9] example. also recognised the antibiotic activity of Penicillium and other fungi in 1877. History Discovery The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in [15] 1928. together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley.

most importantly in the case of penicillin. penicillin was found to be most effective against Gram-positive bacteria. but then he dismissed the fungi. Fleming recounted that the date of his discovery of penicillin was on the morning of Friday. even though his investigations started years before Fleming's. 1928. viruses and other agents was unknown. and ineffective against Gram-negative organisms and fungi.modo que o cheiro infecto não se produz. bacteria. Charles Thom. After further experiments. ou produz-se em proporções infinitamente menores. He grew a pure culture and discovered it was a Penicillium mould. They reported Picado's observations on the inhibitory actions of fungi of the genus Penicillium between 1915 and 1927. em via de regra. Picado reported his discovery to the Paris Academy of Sciences. which was not accepted by the Institut Pasteur because of his youth. He found that it weakened the microbes. He restarted clinical trials in 1934. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of thePenicillium mould. now known to be Penicillium notatum. Fleming concluded that the mould released a substance that repressed the growth and lysing the bacteria. Ascophora and many others) is useful because it feeds on decaying organic matter and destroys putrifaction so that. and the idea that infections were caused by transmissible agents was not widely accepted at the time. In March 2000. Fleming was convinced penicillin could not last long enough in the human body to kill pathogenic bacteria. He expressed initial optimism that penicillin would be a useful disinfectant. doctors at the San Juan de Dios Hospital in San José. Sterilization measures had been shown to limit the outbreak and spread of disease. and continued to try to get someone to [22] purify it until 1940. Mary's Hospital in London (now part of Imperial College). the mechanism of transmission of disease by parasites. how they manage infection once it has begun and. figure 1680. the effect that natural and man-made agents could have on the progress of infection. There was a halo of inhibited bacterial growth around the mould. [20] September 28. It was a fortuitous accident: in his laboratory in the basement of St. Penicillium glaucum. [Translation: "The mould (Penicillium infestans. and Fleming referred the matter to him. as a rule.S. and stopped studying it after 1931. Vincenzo Tiberio. Joseph Lister was experimenting with Penicillum in 1871 for his aseptic surgery. being highly potent with minimal toxicity compared to antiseptics of the day. an American specialist working at the U. Costa Rica. and noted its laboratory value in the isolation of Bacillus [21] influenzae (now Haemophilus influenzae). These early investigations did not lead to the use of antibiotics to treat infection because they took place in obscure circumstances. yet did not patent it. or is produced in infinitely smaller amounts. Fleming noticed a Petri dish containing Staphylococcus plate culture he mistakenly left open. published the manuscripts of the Costa Rican scientist and medical doctorClodomiro (Clorito) Picado Twight (1887–1944). Department of Agriculture. the odour of infection does not occur. was contaminated by bluegreenmould. physician of the University of Naples published a research about a mold ( [18][19] Penicillium ) in a water well that had a antibacterial action. Even in these early stages. which formed a visible growth. Ernest Duchesne documented it in an 1897 paper. however. In the late 19th century. there was increasing knowledge of the mechanisms by which living organisms become infected. was the acknowledged expert. Medical application ."] [17] In 1895.

Approximately 1300 people were infected as part of the study (including orphaned children). University of Oxford made significant progress in showing the in vivobactericidal action of penicillin. insane asylum patients. Sanders) at the Sir William Dunn School of Pathology. to test the effectiveness of penicillin in treating such diseases. In 1939. the National Institutes of Health and the Pan American Health Sanitary Bureau (now theWorld Health Organization's Pan American Health Organization) and the Guatemalan government. He then cured four additional patients (one adult and three infants) of eye infections. but they [24] proved it harmless and effective on mice. John Bumstead and Orvan Hess saved a dying [25][26] patient's life using penicillin.S. Fleming and Chain shared a Nobel Prize in 1945 for their work on penicillin. on November 25. researchers used prostitutes to infect prison inmates. The Presidential Commission for the Study of Bioethical Issues determined that 83 . The study was sponsored by the Public Health Service. 1930. Unethical experimentation In a 1946 to 1948 study in Guatemala.. In 1930. who later participated in the Tuskegee syphilis experiments. he achieved the first recorded cure with penicillin. Orr-Ewing and G. Their attempts to treat humans failed because of insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert Alexander). They later tried infecting people with "direct inoculations made from syphilis bacteria poured into the men's penises and on forearms and faces that were slightly abraded . On March 14. failing to [23] cure a fifth. Cutler chose to do the study in Guatemala because he would not have been permitted to do it in the United [35][36][37][38] States. M. Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford. J. Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain. The team was led by John Charles Cutler. Arthur Duncan Gardner. Norman Heatley. and Guatemalan soldiers with syphilis and other sexually transmitted diseases (STDs). 1942. probably because the drug did not penetrate the skin deeply enough. a pathologist at the Royal Infirmary in Sheffield. These trials continue to be cited by some sources as the first cures using penicillin. attempted to use penicillin to treat sycosis barbae.Florey (pictured). eruptions in beard follicles. Jennings. Moving on to ophthalmia neonatorum.. though the Paine [23] trials took place earlier. or in a few cases through [34] spinal punctures". Cecil George Paine. U. England. but was unsuccessful. a gonococcal infection in infants.

led to the search for derivatives of penicillin that could treat a wider range of infections. but were ineffective against the methicillinresistant Staphylococcus aureus (MRSA) strains that subsequently emerged. . along with the poor activity of the orally active phenoxymethylpenicillin. with various improvements over benzylpenicillin (bioavailability.people died. The first major development was ampicillin. Further development yielded β-lactamase-resistant penicillins. Another development of the line of true penicillins was the antipseudomonal penicillins. it was not possible to determine whether the experiments were the direct [39] cause of death. However. useful for their activity against Gram-negativebacteria. dicloxacillin. the nucleus of penicillin. and methicillin. the cephalosporins. however. stability. The isolation of 6-APA. and piperacillin. tolerance). allowed for the preparation of semisynthetic penicillins. which offered a broader spectrum of activity than either of the original penicillins. the usefulness of the β-lactam ring was such that related antibiotics. These were significant for their activity against βlactamase-producing bacterial species. ticarcillin. Developments from penicillin The narrow range of treatable diseases or "spectrum of activity" of the penicillins. such as carbenicillin. the carbapenems and. including flucloxacillin. including the mecillinams. spectrum. still retain it at the center [40] of their structures. most important.

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