Chapter e1

Ketolides

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Telithromycin, the one available ketolide, is similar in structure to macrolides but has a broader spectrum of activity. Telithromycin offers activity against both penicillin-resistant and macrolide-resistant pneumococci and is equal to azithromycin against atypical pathogens and H influenzae. The dose is 800 mg/d orally, and no adjustment is needed for kidney disease or liver insufficiency. Upon telithromycin’s approval, upper gastrointestinal toxicity and visual disturbances (occurring more frequently in women than men) were the most commonly observed adverse events. However, telithromycin has since been associated with severe hepatotoxicity resulting in liver transplant and death. Telithromycin also has been found to exacerbate myasthenia gravis. Cytochrome P450 inhibition with telithromycin approximates that of erythromycin, and increased serum levels of warfarin and other agents would be expected with concomitant administration of telithromycin. The serious hepatotoxicity of telithromycin significantly limits its use in the treatment of outpatient respiratory tract infection. There is no clear indication for this agent.

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