Using a microbroth method for aerobes and agar dilution for anaerobes, we studied the comparative in vitro activity of gemifloxacin, three fluoroquinolones, two macrolides and two beta-lactams, against 207 aerobic and 162 anaerobic antral sinus puncture isolates. Gemifloxacin was active at < or = 0.25 ug/mL against 198/207 [96%] aerobes and 127/162 [78%] anaerobes or 325/369 [88%] of all isolates and was the most active quinolone on a weight basis against Gram-positive organisms. All Haemophilus and Moraxella species were susceptible to < or =0.06 ug/mL of gemifloxacin. Thirty-five anaerobic isolates [35/162, 22%] required > or =0.5 ug/mL of gemifloxacin for inhibition, including all Prevotella species [all except one strain of P. bivia were susceptible to < or = 2 ug/mL] and occasional strains of Bacteroides uniformis, Bacteroides fragilis, Bilophila wadsworthia, Peptostreptococcus magnus, Peptostreptococcus micros, Propionibacterium acnes, and Veillonella species. All fusobacteria were susceptible to < or =0.25 ug/mL of gemifloxacin. Based on our in vitro study results, we conclude that gemifloxacin may offer a therapeutic alternative for sinus infections.