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INFECTIOUS DISEASES INFECTIOUS DISEASES ANTIBIOTICS ANTIBIOTICS The magic bullets of medicine In a 1945 interview with The New York Times, Alexander Fleming, who won a Nobel Prize that year for his In 1906 German physician and scientist, Dr Paul Ehrlich predicted that chemists would ‘soon be able to produce substances that would seek out specific disease-causing agents’. He called these substances ‘magic bullets’. Twelve years later, Sir Alexander Fleming, fondly known as the ‘sloppy’ lab technician ‘accidentally’ discovered penicillin and changed the course of modern medicine. discovery of pencillin, warned that misuse of the drug could result in selection for resistant bacteria. True to this prediction, resistance began to emerge within 10 1941-1943 years of the wide scale introduction of penicillin Andrew Moyer, Robert Coghill and Kenneth Raper develop methods for industrialised penicillin production and isolated higheryielding strains of the Penicillium fungus Charles Moran and colleagues save Winston Churchill from pneumonia with the use of sulphonamide René Dubos isolates tyrothricin, the first antibiotic in history to show strong antimicrobial activity experimentally in a mouse Fleming discovers penicillin (ß-lactams) Howard Florey and William Dunn show the in vivo bactericidal action of penicillin Florey and Dunn treat a policeman, Albert Alexander, with a severe face infection. At first his condition improves, but supplies run out and he dies 1939 1941 1928 • • • • • Edmund Kornfield receives a soil sample from a missionary friend based in Borneo, which leads to the discovery of the first glycopeptide Dorothy Hodgkin works out the structure of penicillin using X-rays. Knowledge of the structure finally opens new avenues for creating and developing semisynthetic derivatives of penicillin Albert Schatz and Discovery of Selman Waksman fidaxomicin discover a second (targeting Clostridium clinically important Giuseppe Brotzu difficile), the first antibiotic, streptomycin finds a fungus from Scientists in a new class of (aminoglycosides), seawater near a from Japan narrow spectrum effective against sewage outlet in isolates the macrocyclic e.g. Mycobacterium Sardinia and isolates first polymyxin antibiotic drugs tuberculosis the first cephalosporin 1943 • • 1945 • • 1948 • • • • 1932 1940 1942 1944 1947 1949 Florey and Dunn successfully treat bacterial infection in mice John Fulton uses 5.5g of crude penicillin to save the life of Anne Miller who developed septicaemia after a miscarriage Benjamin Duggar reveals the discovery of the first tetracycline Chloramphenicol is discovered as a natural product secreted by the bacterium Streptomyces venezuelae found in soil and compost Abelardo Aguilar from the Philippines isolates erythromycin producing bacteria Resistance to antibiotics first observed (sulfa drugs) 1941-1944 Jasper Kane and colleagues develop the practical, deep-tank fermentation method for production of large quantities of pharmaceutical-grade penicillin 30 August 2016 The Specialist Forum Vol. 16 No. 7 Ehrlich and colleagues discover the first amphenicol Scientists at the Hamao Umezawa develop azomycin, which later leads the the development of metronidazole Lab scientists at UpJohn Company announce the discovery of novobiocin Scientists at the the Rhône-Poulenc Company in France announce the development of metronidazole 1953 1956 1959 1950 Gerhard Domagk tests sulfonamidochrysoidine, first synthesised by chemists Josef Klarer and Fritz Mietzsch Georgyi Gause and his wife, Maria Brazhnikova, discover Gramicidin S. Within a year, all Russian hospitals start to use it MH McCormick and colleagues discover vancomycin • 1952 • • 1955 Hans Oxazolidinone, a Margreiter class of compounds and Ernst containing Brandl develop 2-oxazolidone the first in the structure, acid-stable is discovered penicillin Oral nitrofuran is for oral used for the first administration, time to treat urinary penicillin V tract infections Samuel Kushner and colleagues announce the discovery of pyrazinamide • • • Scientists discover Quinolones, a family a new class of of synthetic broadβ-lactam antibiotics, spectrum antibiotic carbapenems, which drugs, are ‘accidently’ proved able to kill discovered by GY bacteria resistant to Lesher et al other β-lactams 1962 • 1957 1961 John Sheehan of the Massachusetts Institute of Technology completes the first chemical synthesis of penicillin Scientists at UpJohn announce the discovery of Spectinomycin Piero Sensi and Maria Timbal isolate rifamycins from a fermentation culture of Streptomyces mediterranei Scientists at the Umezawa Group in Japan isolate kanamycin. It was a breakthrough drug for killing penicillin and streptomycin resistant bacteria • Lipopetides are discovered. A lipopeptide is a molecule consisting of a lipid connected to a peptide. Bacteria express these molecules. Certain lipopeptides are used as antibiotics 1976 • 1963 1986 • • • 1985 • 1997 Barry Marshall Diarylquinolines, Streptogramin, swallows a petri dish a chemical effective in the of Helicobacter pylori class of drugs treatment of used to treat vancomycin-resistant to prove they caused stomach diseases tuberculosis, Staphylococcus The Lederle aureus, is discovered such as peptic ulcers. are discovered Company announces He cures himself the discovery of with antibiotics etambutol, and antituberculosis drug SOURCES History of the Development of Antibiotics. World of Microbiology and Immunology, 2003. Front Microbiol, 2010. Aminov RI. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future, 2010. Lewis K. Timeline of the discovery and introduction of antibiotics. Nature Reviews Drug Discovery, 2013. White RJ. The early history of antibiotic discovery: Empiricism ruled. Antibiotic Discovery and Development, 2011. Sponsored article. SF The Specialist Forum Vol. 16 No. 7 August 2016 31