Antibiotics -- a Summary

An antibiotic is an agent that either kills or inhibits the growth of a microorganism.

The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.

With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds.  These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems.  Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms: Bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.

History

Before the early 20th century, treatments for infections were based primarily on medicinal folklore.  Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.  Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infectons.  More recent observations made in the laboratory of antibiosis between microorganisms led to the discovery of natural antibacterials produced by microorganisms.  Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".  The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial 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 development of antibacterials began in Germany with Paul Ehrlich in the late 1880s.  Ehrlich noted certain dyes would color human, animal, or bacterial cells, whereas others did not. He then proposed the idea that it might be possible to create chemicals that would act as a selective drug that would bind to and kill bacteria without harming the human host. After screening hundreds of dyes against various organisms, he discovered a medicinally useful drug, the synthetic antibacterial salvarsan now called arsphenamine.

The effects of some types of mold on infection had been noticed many times over the course of history (see: History of penicillin). In 1928, Alexander Fleming noticed the same effect in a Petri dish, where a number of disease-causing bacteria were killed by a fungus of the genus Penicillium. Fleming postulated that the effect is mediated by an antibacterial compound he named penicillin, and that its antibacterial properties could be exploited for chemotherapy. He initially characterized some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists.

The first sulfonamide and first commercially available antibacterial, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 at the Bayer Laboratories of the IG Farben conglomerate in Germany.  Domagk received the 1939 Nobel Prize for Medicine for his efforts. Prontosil had a relatively broad effect against Gram-positive cocci, but not against enterobacteria. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug opened the era of antibacterials.

 

 New Antibiotics Development

In a policy report released by the Infectious Disease Society of America (IDSA) on April 2013, IDSA expressed grave concern over the weak pipeline of antibiotics to combat the growing ability of bacteria, especially the Gram-negative bacilli (GNB), to develop resistance to antibiotics. Since 2009, only 2 new antibiotics were approved in United States, and the number of new antibiotics annually approved for marketing continues to decline. The report could identify only seven antibiotics currently in phase 2 or phase 3 clinical trials to treat the GNB, which includes E. coli, Salmonella, Shigella, and the Enterobacteriaceae bacteria, and these drugs do not address the entire spectrum of the resistance developed by those bacteria. 

http://en.wikipedia.org/wiki/Antibiotics