From 8,419 worldwide clinical isolates of Streptococcus pneumoniae obtained during 1997-1998, 69 isolates with reduced susceptibility or resistance to fluoroquinolones (FQs) were molecularly characterized. For the isolates in this prevalence study, only parC (Ser-793Tyr) and gyrA (Ser-813Phe or Tyr) mutations, especially in combination, were found to contribute significantly to resistance. These mutations influenced the FQ MICs to varying degrees, although the rank order of activity remains independent of mutation type, with ciprofloxacin the least active, followed by levofloxacin, gatifloxacin/grepafloxacin/moxifloxacin/sparfloxacin/trovafloxacin, and clinafloxacin/sitafloxacin. Efflux likely plays a crucial role in reduced susceptibility for new hydrophilic FQs.Streptococcus pneumoniae is a leading cause of illness in humans (32). Recent increases in resistance (4,8,9,(29)(30)(31) have spawned the development of several new fluoroquinolones (FQs) with improved in vitro antipneumococcal activity (1, 7, 10-12, 14, 15, 34, 35). In pneumococci, reports indicate mutations in gyrA, gyrB, parC, and parE to be associated with FQ resistance (16, 18, 20-23, 28, 33). Efflux is also reported to contribute significantly to reduced susceptibility for some hydrophilic FQs, such as ciprofloxacin, while more hydrophobic FQs, like grepafloxacin, appear less affected (5, 13).(This work was presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1999.) This work aimed to define the prevalence of predominant mutations conferring FQ resistance in pneumococci collected during 1 year. Mutations in genes conferring FQ resistance in S. pneumoniae (16, 18, 20-23, 28, 33) have been well studied, but studies have typically included either clinical isolates (few and locally derived) or laboratory-derived mutants. In contrast, this study, the largest molecular surveillance study of FQ resistance in S. pneumoniae to date, comprises clinically significant isolates from locations worldwide, providing the opportunity to characterize the prevalence of mutations globally and their impact on the MICs of several new FQs.A total of 8,419 clinically significant isolates of S. pneumoniae associated with lower respiratory tract or blood infections were derived from 519 geographically distinct hospital laboratories in

The in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin were tested against 72 ciprofloxacin-resistant and 28 ciprofloxacin-susceptible isolates of Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes. Irrespective of the alterations in GyrA and ParC proteins, clinafloxacin exhibited greater activity than all other fluoroquinolones tested against K. pneumoniae and E. aerogenes.