BACTERICIDAL AND INHIBITORY ACTIVITY OF QUINUPRISTIN DALFOPRISTIN AGAINST VANCOMYCIN-RESISTANT AND GENTAMICIN-RESISTANT ENTEROCOCCUS-FAECIUM/

There is a need for new agents, or combinations of agents, for the tre atment of infections caused by vancomycin- and gentamicin-resistant En terococcus faecium (VGREF) that may be resistant to all available anti microbial agents. The early in-vitro activity of quinupristin/??? dalf opristin (30:70)-an injectable streptogramin-encouraged us to test thi s agent against VGREF. By broth dilution, the MICs of quinupristin/dal fopristin against 38 isolates of VGREF ranged from 0.06 mg/L to 2.0 mg /L (mode 0.12 mg/L). The addition of 0.5 mg/L of ciprofloxacin signifi cantly reduced the modal MIC of quinupristin/dalfopristin to 0.015 mg/ L (P=5.75 x 10(-8)). Although the addition of 8.0 mg/L of teicoplanin or 4 mg/L of tetracycline did not significantly reduce the modal MIG, the lowest concentration of the MIC range was reduced from 0.06 to 0.0 15 mg/L, In broth, quinupristin/dalfopristin had slow bactericidal act ivity against the four strains tested over 48 h, with a 1-2 log(10) cf u/mL reduction after 24 h in >1 mg/L of quinupristin/dalfopristin for two strains and >8 mg/L for the two other strains. A mixture of quinup ristin/dalfopristin in a 70:30 ratio was more bactericidal: against on e of the four strains 4-32 mg/L of the combination produced a further 0.5-1.0 log(10) reduction in cfu/mL after 24 h and there was a reducti on of 6.0 log(10) cfu/mL after 48 h for another. By ultracentrifugatio n, the binding of 32 mg/L quinupristin/dalfopristin to human plasma pr otein was 90%, and in plasma broth, 32 mg/L of quinupristin/dalfoprist in maintained bacteriostatic but not bactericidal activity. There is s ome useful synergy with ciprofloxacin and tetracycline, and the activi ty of quinupristin/dalfopristin may be enhanced against some strains b y reversing the concentrations of its two components, quinupristin and dalfopristin, as that may occur in vivo.