In vitro activity of PD 117596-2, a broad-spectrum difluoroquinolone

Abstract

The activity of PD 117596-2, a novel quinolone, was compared to that of other quinolones, ceftazidime, imipenem and gentamicin. PD 117596-2 inhibited mostEnterobacteriaceae at concentrations <0.25 µg/ml, being equal or superior in activity to ciprofloxacin and 2- to 4-fold more active than ofloxacin. It inhibited ceftazidime-resistantEnterobacter spp.,Citrobacter spp. andSerratia marcescens. The MIC90 forPseudomonas aeruginosa, including strains with imipenem MICs of 8 µg/ml and gentamicin MICs > 16 µg/ml, was 0.25 µg/ml. PD 117596-2 was more active than ciprofloxacin againstPseudomonas cepacia andPseudomonas maltophilia, and it inhibitedNeisseria gonorrhoeae andHaemophilus influenzae at < 0.03 µg/ml. PD 117596-2 inhibited staphylococci at 0.5 µg/ml, being 2-fold superior to other quinolones, and with an MIC of 0.25 µg/ml was more active against group A, B, C and G streptococci andStreptococcus pneumoniae. MICs forBacteroides spp. were 2 µg/ml compared to 8–32 µg/ml for other agents. The frequency of spontaneous resistance was low (< 10⁻¹⁰). Differences in MICs and MBCs were within one dilution, and there was a minimal effect of inoculum size. Although PD 117596-2 was less active at pH 5.5, MICs were < 0.5 µg/ml.