Comparative in vitro activity and killing effect of trovafloxacin, DU-6859a, levofloxacin and sparfloxacin against Staphylococcus aureus - Focus on methicillin-resistant isolates

The predominance of quinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in the nosocomial environment led to the in vitro comparison of trovafloxacin (CP-99,219) and DU-6859a (which are novel fluoroquinolone compounds) with levofloxacin (the L-geometric isomer of ofloxacin) and sparfloxacin against 152 S. aureus isolates, 104 of which were MRSA. At 2 mg/L trovafloxacin and DU-6859a inhibited 92.3 and 77.9% of MRSA isolates, respectively, possessing lower minimum inhibitory concentration (MIG) and minimum bactericidal concentration (MBC) values than levofloxacin and sparfloxacin, which inhibited 38.5 and 36.5% of isolates, respectively. In contrast, in the methicillin-susceptible population all tested fluoroquinolones had an equal intrinsic activity. Trovafloxacin possessed a superior killing effect compared with DU-6859a and sparfloxacin, whereas levofloxacin was the least bactericidal quinolone. Indeed, the effect of trovafloxacin was mainly expressed at a quinolone concentration of 2 x MIC and after 24 hours of growth. However, in levofloxacin- and sparfloxacin-resistant MRSA isolates, DU-6859a had a superior killing effect compared with travofloxacin. Trovafloxacin had a killing effect in only 20% of DU-6859a-, levofloxacin- and sparfloxacin-resistant isolates. Our findings support trovafloxacin and DU-6859a as highly active in vitro antistaphylococcal agents especially in MRSA, which merit further clinical investigation.