Modulation of efficacies and pharmacokinetics of antibiotics by granulocyte colony-stimulating factor in neutropenic mice with multidrug-resistant Enterococcus faecalis infection
Co. Onyeji et al., Modulation of efficacies and pharmacokinetics of antibiotics by granulocyte colony-stimulating factor in neutropenic mice with multidrug-resistant Enterococcus faecalis infection, J ANTIMICRO, 46(3), 2000, pp. 429-436
It has been demonstrated previously that, in non-neutropenic animals, inter
feron-gamma markedly enhances the efficacies of gentamicin and vancomycin a
gainst Enterococcus faecalis resistant to these antibiotics. The aim of our
study was to determining whether granulocyte colony-stimulating factor (G-
CSF) can be beneficial as an adjunct to gentamicin and vancomycin in the tr
eatment of the same infection in neutropenic mice. After induction of neutr
openia by cyclophosphamide, mice were inoculated ip with the organism. The
infected animals received sc administrations of G-CSF, antibiotic or a comb
ination of both agents at determined dosing regimens. Infected animals trea
ted with G-CSF alone showed a dose-dependent increase in survival. The inoc
ulum size used in establishing infection affected the effectiveness of the
cytokine. Survival was significantly (P < 0.01) better in the infected anim
als given gentamicin and vancomycin plus G-CSF than in those given antibiot
ics or G-CSF alone. The possibility of pharmacokinetic interaction between
G-CSF and each of the antibiotics was examined. The cytokine significantly
increased the plasma clearance of gentamicin, with a resultant decrease in
the area under the concentration-time curve (AUC), while the disposition of
vancomycin was not affected. This study suggests that G-CSF may be a usefu
l adjunct to gentamicin and vancomycin for the treatment of multidrug-resis
tant E. faecalis infection in neutropenic patients.