Telithromycin (a ketolide) was largely withdrawn from use due to serious hepatotoxicity. However, its mechanism of binding to bacterial ribosomes was superior to macrolides because:

• A Telithromycin binds to the 30S ribosomal subunit unlike macrolides
• B Telithromycin irreversibly crosslinks the 50S and 30S subunits
• C Telithromycin has two binding sites on the 50S ribosomal subunit (domain II and V of 23S rRNA), overcoming erm-mediated methylation resistance that only modifies domain V ✓
• D Telithromycin activates autolysins even at sub-MIC concentrations

Explanation

Macrolide resistance via methylases encoded by erm (erythromycin ribosome methylation) genes modifies adenine residue A2058 in domain V of 23S rRNA, preventing macrolide binding. Telithromycin, unlike erythromycin-type macrolides, has an additional binding site at domain II (loop region of 23S rRNA) via its carbamate side chain. This dual-domain binding allows telithromycin to retain ribosomal inhibitory activity even when the domain V target is methylated by ErmB or ErmC. Despite this mechanistic advantage, telithromycin's hepatotoxicity (due to its pyridyl-imidazole group interacting with nicotinic acetylcholine receptors causing liver toxicity) led to restricted use.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.