BACKGROUND Streptococcus pneumoniae is a leading pathogen causing pneumonia, meningitis, otitis media, bacteremia and sinusitis resulting in significant morbidity and mortality. We examined in vitro activities of five quinolones in comparison with other antibiotics against 85 invasive pneumococcal isolates. METHODS Minimal inhibitory concentrations (MICs) of penicillin G, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulfamethoxazole (SXT), ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin and gemifloxacin were determined using a broth microdilution method. RESULTS The overall rates of resistance to penicillin (46%), cefuroxime (20%), azithromycin (20%), clarithromycin (18%) and SXT (46%) were considerable. Among all of the isolates, 9 isolates (11%) were highly resistant (MIC >/=2 mg/l) and 30 isolates (35%) had intermediate resistance (MIC 0.12- 1.0 mg/l). Of the quinolones gemifloxacin and trovafloxacin had the highest activity. The penicillin resistance status of the isolates did not have any effect on the resistance pattern of new quinolones. CONCLUSION The new quinolones show great potential in the treatment of invasive infections caused by both penicillin-susceptible and penicillin-resistant pneumococci.