A study of the comparative in vitro activity of telithromycin, a new ketolide, against 155 aerobic and 171 anaerobic antral sinus puncture isolates showed it to be active against a broad range of sinus pathogens. All pneumococci, including erythromycin-resistant strains, were susceptible to telithromycin at < or = 0.5 microg/ml; all Haemophilus influenzae and Eikenella corrodens strains were inhibited by < or = 4 microg of telithromycin/ml; all Moraxella spp. and beta-lactamase-producing Prevotella species strains were inhibited by < or = 0.25 and 0.5 microg of telithromycin/ml, respectively. Among all anaerobes tested, 94% (160 of 171 strains) were susceptible to < or = 4 microg of telithromycin/ml; however, 8 of 17 (47%) Fusobacterium strains, 2 Veillonella strains, and 1 Peptostreptococcus micros strain required > 4 microg of telithromycin/ml for inhibition. Telithromycin may offer a therapeutic alternative for sinus infections, including those due to erythromycin-resistant pneumococci.