Antibiotics
Antibiotics
Antibiotics
that kills, or inhibits the growth of, bacteria. Antibiotics belong to the broader group of antimicrobial compounds, used to treat infections caused by microorganisms, including fungi and protozoa.
The term "antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.
This original definition excluded naturally occurring substances that kill bacteria but are not produced by microorganisms (such as gastric juice and hydrogen peroxide) and also excluded synthetic antibacterial compounds such as the sulfonamides.
Testing the susceptibility of Staphylococcus aureus to antibiotics by the Kirby-Bauer disk diffusion method. Antibiotics diffuse out from antibioticcontaining disks and inhibit growth of S. aureus resulting in a zone of inhibition
With advances in medicinal chemistry, most antibiotics are now semisyntheticmodified chemically from original compounds found in nature, as is the case with beta-lactams (which include the penicillins, produced by fungi in the genus Penicillium, the cephalosporins, and the carbapenems). Some antibiotics are still produced and isolated from living organisms, such as the aminoglycosides, and others have been created through purely synthetic means: the sulfonamides, the quinolones, and the oxazolidinones.
Originally known as antiobiosis, antibiotics were drugs that had actions against bacteria. The term antibiosis which means against life was introduced by the French bacteriologist Vuillemin as a descriptive name of the phenomenon exhibited by these drugs. (Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis). These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist in 1942.
Synthetic antibiotic chemotherapy as a science and the story of antibiotic development began in Germany with Paul Ehrlich, a German medical scientist in the late 1880s. Dr. Ehrlich noted that certain dyes would bind to and color human, animal or bacterial cells, while others did not. He then extended the idea that it might be possible to make certain dyes or chemicals that would act as a magic bullet or selective drug that would bind to and kill bacteria while not harming the human host. After much experimentation, screening hundreds of dyes against various organisms, he discovered a medicinally useful drug, the man-made antibiotic, Salvarsan. However, the adverse side-effect profile of salvarsan, coupled with the later discovery of the antibiotic penicillin, superseded its use as an antibiotic.
Paul Ehrlich (14 March 1854 20 August 1915) was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus". He coined the term "chemotherapy" and popularized the concept of a "magic bullet". Sahachir Hata ( Hata Sahachir?, March 23, 1873 November 22, 1938) was a Japanese bacteriologist who developed the Arsphenamine drug in 1909 in the laboratory of Paul Ehrlich.
Sahachiro Hata discovered the anti-syphilitic activity of this compound in 1908 in the laboratory of Paul Ehrlich, during a survey of hundreds of newly-synthesized organic arsenical compounds.
Arsphenamine was marketed under the trade name Salvarsan in 1910. It was also called 606, because it was the 606th compound synthesized for testing. Salvarsan was the first organic anti-syphillitic, and a great improvement over the inorganic mercury compounds that had been used previously. A more soluble (but slightly less effective) arsenical compound, Neosalvarsan, (neoarsphenamine), became available in 1912. These arsenical compounds came with considerable risk of side effects, and they were supplanted as treatments for syphilis in the 1940s by penicillin.
Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum subspecies pallidum. The route of transmission of syphilis is almost always through sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero.
The work of Ehrlich, which marked the birth of the antibiotic revolution, was followed by the discovery of Prontosil by Domagk in 1932. Prontosil, the first commercially available antibacterial antibiotic was developed by a research team led by Gerhard Domagk (who received the 1939 Nobel Prize for Medicine for his efforts) at the Bayer Laboratories of the IG Farben conglomerate in Germany. Prontosil had a relatively broad effect against Gram-positive cocci . The discovery and development of this first sulfonamide drug opened the era of antibiotics.
Gerhard Johannes Paul Domagk (30 October 1895 24 April 1964) was a German pathologist and bacteriologist credited with the discovery of Sulfonamidochrysoidi ne (KI-730) the first commercially available antibacterial antibiotic (marketed under the brand name Prontosil) for which he received the 1939 Nobel Prize in Physiology or Medicine.
He was appointed the director of Bayer's Institute of Pathology and Bacteriology, where he continued the studies of and , based on works by Paul Ehrlich, to use dyes, at that time a major product of IG Farben, as antibiotics. He found the sulfonamide Prontosil to be effective against streptococcus, and treated his own daughter with it, saving her the amputation of an arm.
Alexander Fleming's discovery of Penicillin in 1928. Even then the therapeutic potential of penicillin was not pursued.
More than ten years later, Florey and Chain succeeded in purifying penicillin. The purified antibiotic displayed antibacterial activity against a wide range of bacteria. It also had low toxicity and could be taken without causing adverse effects. Furthermore its activity was not inhibited by biological constituents such as pus, unlike the synthetic antibiotic class available at the time the sulfonamides. The discovery of such a powerful antibiotic was unprecedented. The development of penicillin led to renewed interest in the search for antibiotic compounds with similar capabilities. Because of their discovery of penicillin Ernst Chain, Howard Florey and Alexander Fleming shared the 1945 Nobel Prize in Medicine.
"When I woke up just after dawn on September 28, 1928, I certainly didn't plan to revolutionize all medicine by discovering the world's first antibiotic, or bacteria killer," Fleming would later say, "But I guess that was exactly what I did".
By 1928, Fleming was investigating the properties of staphylococci. On 3 September 1928, Fleming returned to his laboratory having spent August on vacation with his family. Before leaving he had stacked all his cultures of staphylococci on a bench in a corner of his laboratory. On returning, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci that had immediately surrounded it had been destroyed, whereas other colonies further away were normal. Fleming identified the mould that had contaminated his culture plates as being from the Penicillium genus, andafter some months' of calling it "mould juice" named the substance it released penicillin on 7 March 1929.
Penicillin
Medical application
In 1930 Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use penicillin to treat sycosis barbaeeruptions in beard follicles, but was unsuccessful, probably because the drug did not penetrate the skin deeply enough. Moving on to ophthalmia neonatorum a gonococcal infection in infants he achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, failing to cure a fifth.
A newborn with gonococcal ophthalmia neonatorum.
Mass production The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s.
Mechanism of action Main article: Beta-lactam antibiotic -Lactam antibiotics work by inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall. The -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). 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-negative bacteria do not lose their cell wall completely and are called spheroplasts after treatment with penicillin.
Adverse effects urotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.11%
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a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tube
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