In-vitro activity of moxifloxacin against fluoroquinolone-resistant strains of aerobic Gram-negative bacilli and Enterococcus faecalis

MICs of the new fluoroquinolone, moxifloxacin, and those of ciprofloxacin, ofloxacin and sparfloxacin for 19 genetically characterized fluoroquinolone -resistant strains were determined by the agar dilution method. The MICs of moxifloxacin for Escherichia isolates with one mutation in gyrA (correspon ding to Ser83-->Leu or Asp87-->Gly substitution) were 0.25-0.5 mg/L, while those of ciprofloxacin, ofloxacin and sparfloxacin were 0.06-0.25, 1 and 0. 12-0.5 mg/L, respectively. These values were four- to 16-fold higher than t hose of the same antibiotics for the wild-type strain, E. coli KL16. Simila r results were observed with clinical isolates of Salmonella spp. harbourin g one mutation in gyrA leading to the substitution of Ser83 by Phe or Tyr. In the presence of two mutations in the E. coli gyrA gene, the MICs of moxi floxacin ciprofloxacin, ofloxacin and sparfloxacin were 2, 0.5, 4 and 1 mg/ L, respectively; these were 32 times higher than the MICs of these agents f or E. coli KL16. The MICs of the four quinolones for triple mutants with tw o mutations in gyrA and one in parC were even higher, i.e. 8, 8, 16 and 8-1 6 mg/L, respectively. The MICs of moxifloxacin for Campylobacter coli and C ampylobacter jejuni strains with a gyrA mutation leading to Thr86-->IIe sub stitution ranged from 1 to 2 mg/L, while the MICs of ciprofloxacin, ofloxac in and sparfloxacin were 16-32 mg/L, 8-16 and 4-8 mg/L, respectively. For h igh-level ciprofloxacin-resistant (MICs of 32 mg/L) clinical isolates of En terococcus faecalis with one substitution at position 83 in GyrA (E. coli c oordinates), the MICs of moxifloxacin, ofloxacin and sparfloxacin were 8-16 , greater than or equal to 128 and 32 mg/L respectively. In conclusion, mox ifloxacin and ct her fluoroquinolones exhibit cross-resistance against aero bic Gram-negative bacilli and enterococci. The in-vitro activity of moxiflo xacin was greater than that of ofloxacin and slightly less than that of cip rofloxacin and sparfloxacin against Enterobacteriaceae, but greater than th ose of the three other compounds tested against Campylobacter spp and E. fa ecalis.