Ketolide

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Telithromycin Telithromycin.png
Telithromycin

Ketolides are antibiotics belonging to the macrolide group. Ketolides are derived from erythromycin by substituting the cladinose sugar with a keto-group and attaching a cyclic carbamate group in the lactone ring. [1] These modifications give ketolides much broader spectrum than other macrolides. Moreover, ketolides are effective against macrolide-resistant bacteria, due to their ability to bind at two sites at the bacterial ribosome as well as having a structural modification that makes them poor substrates for efflux-pump mediated resistance. [2]

Ketolides block protein synthesis by binding to ribosomal subunits and may also inhibit the formation of newly forming ribosomes. According to a recent study comparing the action of the classic macrolides erythromycin and azithromycin with ketolides, which are used to treat serious infections, the more powerful drugs (ketolides) were the more "leaky" in blocking the production of proteins. The researchers were surprised to discover that ketolides, which are known to be better antibiotics, allow for many more proteins to be made compared to the older, less efficient macrolides. As a result, it is now believed that allowing cells to make some proteins could be much more damaging for a microbe than not letting it make any proteins at all. The findings may point the way to better and more potent antibiotics.

The only ketolide on the market at this moment is telithromycin, which is sold under the brand name of Ketek. Other ketolides in development include cethromycin and solithromycin.

Medical uses

Ketolides are used to treat community-acquired bacterial pneumonia. Other respiratory tract infections were removed as indications when it was recognized that use of telithromycin can result in hepatitis and liver failure.

Related Research Articles

Erythromycin Chemical compound

Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used during pregnancy to prevent Group B streptococcal infection in the newborn, as well as to improve delayed stomach emptying. It can be given intravenously and by mouth. An eye ointment is routinely recommended after delivery to prevent eye infections in the newborn.

Macrolide

The macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Macrolides are bacteriostatic in that they suppress or inhibit bacterial growth rather than killing bacteria completely.

Tetracycline Antibiotic used to treat a number of infections

Tetracycline, sold under the brand name Sumycin among others, is an antibiotic used to treat a number of infections. This includes acne, cholera, brucellosis, plague, malaria, and syphilis. It is taken by mouth.

Clarithromycin

Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.

Oxytetracycline Antibiotic

Oxytetracycline was the second of the broad-spectrum tetracycline group of antibiotics to be discovered.

Aminoglycoside

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.

Clindamycin

Clindamycin is an antibiotic used for the treatment of a number of bacterial infections, including bone or joint infections, pelvic inflammatory disease, strep throat, pneumonia, middle ear infections, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used for malaria. It is available by mouth, by injection into a vein, and as a cream to be applied to the skin or in the vagina.

Azithromycin Antibiotic

Azithromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections. It can also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections. Along with other medications, it may also be used for malaria. It can be taken by mouth or intravenously with doses once per day.

Roxithromycin

Roxithromycin is a semi-synthetic macrolide antibiotic. It is used to treat respiratory tract, urinary and soft tissue infections. Roxithromycin is derived from erythromycin, containing the same 14-membered lactone ring. However, an N-oxime side chain is attached to the lactone ring. It is also currently undergoing clinical trials for the treatment of male-pattern hair loss.

Telithromycin

Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treat community acquired pneumonia of mild to moderate severity. After significant safety concerns, the US Food and Drug Administration sharply curtailed the approved uses of the drug in early 2007.

Lincosamides

Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.

Pristinamycin

Pristinamycin (INN), also spelled pristinamycine, is an antibiotic used primarily in the treatment of staphylococcal infections, and to a lesser extent streptococcal infections. It is a streptogramin group antibiotic, similar to virginiamycin, derived from the bacterium Streptomyces pristinaespiralis. It is marketed in Europe by Sanofi-Aventis under the trade name Pyostacine.

Tetracycline antibiotics

Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named for their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloride, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.

Oleandomycin

Oleandomycin is a macrolide antibiotic. It is synthesized from strains of Streptomyces antibioticus. It is weaker than erythromycin.

Spiramycin

Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico, spiramycin is still considered an experimental drug in the United States, but can sometimes be obtained by special permission from the FDA for toxoplasmosis in the first trimester of pregnancy. Another treatment option are a combination of pyrimethamine and sulfadiazine.

Protein synthesis inhibitor

A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.

Tylosin

Tylosin is a macrolide antibiotic and bacteriostatic feed additive used in veterinary medicine. It has a broad spectrum of activity against Gram-positive organisms and a limited range of Gram-negative organisms. It is found naturally as a fermentation product of Streptomyces fradiae.

A pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae, which is also called the pneumococcus. S. pneumoniae is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. However, it is also a cause of significant disease, being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimates that in 2005 pneumococcal infections were responsible for the death of 1.6 million children worldwide.

Streptogramin A is a group of antibiotics within the larger family of antibiotics known as streptogramins. They are synthesized by the bacteria Streptomyces virginiae. The streptogramin family of antibiotics consists of two distinct groups: group A antibiotics contain a 23-membered unsaturated ring with lactone and peptide bonds while group B antibiotics are depsipeptides. While structurally different, these two groups of antibiotics act synergistically, providing greater antibiotic activity than the combined activity of the separate components. These antibiotics have until recently been commercially manufactured as feed additives in agriculture, although today there is increased interest in their ability to combat antibiotic-resistant bacteria, particularly vancomycin-resistant bacteria.

Solithromycin

Solithromycin is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections.

References

  1. Scheinfeld, N (July 2004). "Telithromycin: a brief review of a new ketolide antibiotic" . Journal of Drugs in Dermatology. 3 (4): 409–13. PMID   15303785.
  2. Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor Basic & Clinical Pharmacology, 11e McGraw-Hill 2009 via "accessmedicine.com"