Antibiotics Antibiotics, a category of antiinfective drugs, are chemical substances produced by microorganisms such as bacteria and fungi that at low concentrations kill or inhibit other microorganisms. The development of antibiotic drugs was one of the most important advances in twentieth century medicine. Penicillin, the first antibiotic, was first produced in the U.S. in 1942. About the same time new antibiotics, including streptomycin, were discovered in a mixture of microbial substances from a soil bacillus. Many of these drugs were found to be specific in their action but in 1947, chloramphenicol, the first so-called broad spectrum antibiotic was discovered; followed in 1948 by aureomycin, the first broad spectrum tetracycline antibiotic. Chloramphenicol, a nitrobenzene derivative of dichloroacetic acid, is manufactured synthetically and used to treat typhoid fever and severe infections caused by penicillin-resistant microorganisms. As antibiotics destroyed the more common pathogens, highly resistant strains that escape destruction began to pose problems, and new antibiotics were required to eradicate them. By the end of the twentieth century, there were well over 10,000 known antibiotics ranging from simple to extremely complex substances. This great expansion in new antibiotics was achieved through successful synthetic modifications, and many antibiotics are now manufactured in quantity. This approach has been especially successful with antibiotics whose molecular structure contains the four- member b-lactam ring, including the penicillins and cephalosporins that currently account for over 60 percent of world production of antibiotics. The modes of action of different antibiotics vary, though many destroy bacteria by inhibiting cell-wall biosynthesis. Bacterial cells, unlike animal cells, have a cell wall surrounding a cytoplasmic membrane. The cell wall is produced from components within the cell that are transported through the cell membrane and built into the cell wall, and antibiotics that interfere with this process inhibit cell growth. For example, the b-lactam ring in penicillin and cephalosporin molecules interferes with the final stage in the assembly of the cell wall. Other antibiotics inhibit protein synthesis in bacteria, while others act by combining with phos pholipids in the cell membrane to interfere with its function as a selective barrier and allow essential materials in the cell to leak out. This results in the death of the bacterial cell; but since similar phospholipids are found in mammalian cells, this type of antibiotic is toxic and must be used with care. One antibiotic, rifampin, disrupts RNA synthesis in bacterial cells by combining with enzymes in the cell; as its affinity for bacterial enzymes is greater than for mammalian ones, the latter remain largely unaffected at therapeutic dosages. Penicillin is the safest of all antibiotics, although some patients show hypersensitivity toward it, and this results in adverse reactions. Moreover some microorganisms, notably the staphylococci, develop resistance to naturally occurring penicillin, and this has led to the production of new synthetic modifications. Thus there are two groups of penicillins, those that occur naturally and the semisynthetic penicillins made by growing the Penicillium mold in the presence of certain chemicals. To increase the usefulness of the penicillins, the broad-spectrum penicillins were developed to treat typhoid and enteric fevers and certain infections of the urinary tract. Nevertheless, the naturally occurring penicillins are still the drugs chosen for treating many bacterial infections. The cephalosporins, discovered in the 1950s by Sir Edward Abraham, are relatively nontoxic blactam antibiotics. Like penicillin they were first isolated from a fungus, but later modifications of the b-lactam ring have resulted in over 20 variations grouped according to their activity. The first generation cephalosporins were used for patients who had developed sensitivity to penicillin. They were active against many bacteria including Escherichia coli, but they had to be replaced by second and third generation drugs as resistance began to develop. They have been used for treating pulmonary infections, gonorrhea, and meningitis. The aminoglycosides, which include streptomycin (discovered in 1944), inhibit protein biosynthesis. They are poorly absorbed from the gastrointestinal tract and are administered by intramuscular injection. Streptomycin was among the first of the aminoglycosides to be discovered and is still used together with penicillin for treating infections of the heart valves. Other aminoglycosides are used for treating meningitis, septicemia, and urinary tract infections, but the narrow magrin between a therapeutic and a toxic dose poses difficult problems, and the risks increase with age. The antimicrobial activity of the tetracyclines, another group of synthetic antibiotic drugs, depends on the fact that although they inhibit protein biosynthesis in both bacterial and animal cells, bacteria allow the tetracyclines to penetrate the cell, whereas animal cells do not. Tetracyclines are absorbed from the gastrointestinal tract and can be given orally. In addition to their uses in medicine, antibiotics have also had important veterinary applications and are used as animal feed supplements to promote growth in livestock. Tetracyclines make up about half the sales of antibiotics as supplements, which surpasses all other agricultural applications, but many other antibiotics are also used for this purpose. It is thought that feed antibiotics may promote growth by preventing disease. Another important agricultural use of antibiotics is in their use as antiparasitic agents against both worms and other parasites in the gastrointestinal tract and against ectoparasites such as mites and ticks. In addition to the biochemical antibiotics, the sulfonamides, synthetic chemotherapeutic agents, are also used in treating bacterial diseases. The first sulfonamide was prontosil, introduced in 1932 to combat streptococcal infections. The sulfonamides are broad-spectrum agents that were widely used prior to antibiotics. They work by preventing the production of folic acid, which is essential for the synthesis of nucleic acids. The reaction is reversible causing the inhibition but not the death of the microorganisms involved. Their use has diminished due to the availability of better and safer antibiotics, but they are still used effectively to treat urinary tract infections and malaria and to prevent infection after burns. Related to the sulfonamides, the sulfones are also inhibitors of folic acid biosynthesis. They tend to accumulate in the skin and inflamed tissue, and as they are retained in the tissue for long periods, they are useful in treating leprosy. There are also some other chemical synthesized drugs that show antibacterial properties and find specific clinical uses.