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218 Jain et al.the polypeptide (P) site. However, some drugs in this family (14 and 16 memberedstructures) also bind several proteins in the 50S subunit (1) and this may alsocontribute to their antibacterial effect. Macrolides are also known to weaken thenonspecific binding between the ribosome and the peptidyl-tRNA promotingdisassociation (3). The mechanism of action of ketolides is similar to macrolidesand they also inhibit protein synthesis by interacting with the peptidyl transferasesite of the 50S subunit (4,5). Both macrolides and ketolides interact within domainsII and V of the 23S rRNA, binding in a 1:1 ratio. Within their binding site on thebacterial ribosome, ketolides interact with two regions of the 23S rRNA. Telithromycinbinds to A752 in addition to A2058 bound by erythromycin and othermacrolides and azalides (Fig. 1) (7,8). Blurry vision, unmasking and worsening ofmyasthenia gravis and acute hepatotoxicity have been noted with use of telithromycin.This has led to loss of its indication for AECB and acute bacterial sinusitis.Though it still has an indication for CAP, it is not to be used in patients withmyasthenia gravis. In the latest CAP guidelines, final recommendations fortelithromycin are pending safety evaluation by the FDA (93).The ketolides display a higher affinity than macrolides for forming interactionswith the ribosome (9,10). Ketolides also have a significant inhibitory effect onthe formation of the 50S ribosomal subunits (4,11). Ketolides have been shown toABUAG G CC AG C752A A A U UA GC AUAAA U745A GGT v7482060 A CG2058 A AAAGACGGU C U CCA U CUGA752G745G748C12C11C6A2058CG748G352G748G352G345A2058G345A2058FIGURE 1 Within their binding site on the bacterial ribosome, ketolides interact with two regionsof the 23S rRNA. The C11, 12 carbamate extension of telithromycin additionally spans thedistance across the channel to bind with A752 in addition to A2058. (A) Secondary structures ofthe nucleotides that make up the target site, with the relevant portions of domain II in blue on theleft and those of domain V in green on the right. (B) Cross-section of the ribosomal tunnel, showingerythromycin (orange) bound within the macrolide- and ketolide-binding site. (C) Stereo viewshowing the perspective of the domain II and V nucleotides that makes up the macrolide- andketolide-binding site. Source: From Ref. 6.