Activity of gatifloxacin against strains resistant to ofloxacin and ciprofloxacin and its ability to select for less susceptible bacterial variants

Gatifloxacin is an 8-methoxy fluoroquinolone. On quinolones, this side chain imparts increased activity against Gram-positive bacteria and enhanced killing. Gatifloxacin was tested against ofloxacin non-susceptible (ofloxacin MIC > 2 mg/l) strains of Streptococcus pneumoniae (gatifloxacin MIC90 1 mg/l) and methicillin-resistant Staphylococcus aureus (MRSA, gatifloxacin MIC90, 4 mg/l), and to ciprofloxacin non-susceptible (ciprofloxacin MIC > 1 mg/l) strains of Escherichia coli (gatifloxacin MIC90 > 16 mg/l) and ciprofloxacin non-susceptible (ciprofloxacin MIC > 0.06 mg/l) Neisseria gonorrhoeae (gatifloxacin MIC50 0.12 mg/l and MIC90 0.5 mg/l). Though gatifloxacin showed some reduced susceptibility to these populations, the MIC50 and MIC50 values suggest that gatifloxacin may be useful against pneumococci and some gonococcal strains not susceptible to other fluoroquinolones. Gatifloxacin did not select for less susceptible variants of MRSA and pneumococci, in contrast to the 10- to 100-fold higher selection frequencies with ciprofloxacin and ofloxacin. The single-step E. coli mutants selected by gatifloxacin and the comparator quinolones had quinolone MICs within the susceptible range. These data suggest that gatifloxacin use may hinder the development of quinolone-resistance, particularly in Gram-positive bacteria. (C) 2001 Elsevier Science BN. and International Society of Chemotherapy. All rights reserved.