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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.

References

^ http://findarticles.com/p/articles/mi_m0PDG/is_4_3/ai_n12417033/ Telithromycin: a brief review of a new ketolide antibiotic. 2004
^ Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor Basic & Clinical Pharmacology, 11e McGraw-Hill 2009 via "accessmedicine.com"

External links

Ketek Company Drugs Page

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1. マクロライド系剤、アザライド系剤、リンコサミン系剤、およびケトライド系剤に対する肺炎レンサ球菌の耐性 resistance of streptococcus pneumoniae to the macrolides azalides lincosamines and ketolides
2. アジスロマイシン、クラリスロマイシン、およびテリスロマイシン azithromycin clarithromycin and telithromycin
3. 重症筋無力症の治療 treatment of myasthenia gravis
4. 成人における市中肺炎の治療に関する抗菌薬の研究 antibiotic studies for the treatment of community acquired pneumonia in adults
5. ウィップル病 whipples disease

English Journal

ClpP-Independent Function of ClpX Interferes with Telithromycin Resistance Conferred by Msr(A) in Staphylococcus aureus.

Vimberg V1, Lenart J1, Janata J1, Balikova Novotna G2.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2015 Jun;59(6):3611-4. doi: 10.1128/AAC.04367-14. Epub 2015 Mar 23.
The ABCF family protein Msr(A) confers high resistance to macrolides but only low resistance to ketolides in staphylococci. Mutations in conserved functional regions of ClpX as well as deletion of clpX significantly increased Msr(A)-mediated resistance to the ketolide antibiotic telithromycin. ClpX
PMID 25801573

The slow dissociation rate of K-1602 contributes to the enhanced inhibitory activity of this novel alkyl-aryl-bearing fluoroketolide.

Krokidis M1, Bougas A, Stavropoulou M, Kalpaxis D, Dinos GP.
Journal of enzyme inhibition and medicinal chemistry.J Enzyme Inhib Med Chem.2015 Mar 25:1-6. [Epub ahead of print]
Ketolides belong to the latest generation of macrolides and are not only effective against macrolide susceptible bacterial strains but also against some macrolide resistant strains. Here we present data providing insights into the mechanism of action of K-1602, a novel alkyl-aryl-bearing fluoroketol
PMID 25807301

Inhalation of macrolides: a novel approach to treatment of pulmonary infections.

Siekmeier R1, Hofmann T, Scheuch G.
Advances in experimental medicine and biology.Adv Exp Med Biol.2015;839:13-24. doi: 10.1007/5584_2014_50.
Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of an
PMID 25252902