ketolides

Ketolides are a class of semi-synthetic macrolide antibiotics developed to address macrolide resistance. They are derived from erythromycin by introducing a ketone-containing modification, typically replacing the cladinose sugar with a C3 ketone, which enhances ribosome binding and activity.

Mechanism of action: Ketolides bind to the 50S subunit of the bacterial ribosome at the peptidyl transferase center and adjacent sites, inhibiting translocation and elongation of the nascent polypeptide. Compared with classical macrolides, they form additional contacts with the 23S rRNA and ribosomal proteins such as L22, enabling higher affinity and activity against strains that carry certain resistance determinants.

Spectrum and clinical use: Ketolides show activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and atypical pathogens such as Mycoplasma pneumoniae and Chlamydophila pneumoniae. They retain activity against some macrolide-resistant strains and have been used for community-acquired pneumonia, acute bacterial sinusitis, and acute bronchitis. Their use is generally tempered by safety considerations and the availability of alternative agents.

Safety and regulatory status: Telithromycin, the first ketolide, has been associated with rare but serious liver injury, as well as concerns about visual disturbances and QT prolongation. Regulatory agencies have issued warnings and restricted certain uses, and safety concerns have limited the development and approval of other ketolides. Ketolides can interact with other drugs via CYP3A4 metabolism. As a result, they are now used infrequently and primarily in situations where other antibiotics are unsuitable.