Journal of Antimicrobial Chemotherapy, Vol 39, 23-28, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
RL Hill, CT Smith, M Seyed-Akhavani and MW Casewell
There is a need for new agents, or combinations of agents, for the
treatment of infections caused by vancomycin- and gentamicin-resistant
Enterococcus faecium (VGREF) that may be resistant to all available
antimicrobial agents. The early in-vitro activity of
quinupristin/dalfopristin (30:70)--an injectable streptogramin-- encouraged
us to test this agent against VGREF. By broth dilution, the MICs of
quinupristin/dalfopristin 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 significantly 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 MIC, the lowest concentration of the MIC
range was reduced from 0.06 to 0.015 mg/L. In broth,
quinupristin/dalfopristin had slow bactericidal activity against the four
strains tested over 48 h, with a 1-2 log10 cfu/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 quinupristin/dalfopristin in a
70:30 ratio was more bactericidal: against one of the four strains 4-32
mg/L of the combination produced a further 0.5-1.0 log10 reduction in
cfu/mL after 24 h and there was a reduction of 6.0 log10 cfu/mL after 48 h
for another. By ultracentrifugation, the binding of 32 mg/L
quinupristin/dalfopristin to human plasma protein was 90%, and in plasma
broth, 32 mg/L of quinupristin/dalfopristin maintained bacteriostatic but
not bactericidal activity. There is some useful synergy with ciprofloxacin
and tetracycline, and the activity of quinupristin/dalfopristin may be
enhanced against some strains by reversing the concentrations of its two
components, quinupristin and dalfopristin, as that may occur in vivo.
ORIGINAL ARTICLES
Bactericidal and inhibitory activity of quinupristin/dalfopristin against vancomycin- and gentamicin-resistant Enterococcus faecium
Joint Microbiology Research Unit, Dulwich Public Health Laboratory & Medical Microbiology, King's College School of Medicine and Dentistry, London, UK.
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