Interferon-γ effects on activities of gentamicin and vancomycin against Enterococcus faecalis resistant to the drugs: an in vitro study with human neutrophils

Abstract

The emergence of multidrug-resistant enterococci presents a major therapeutic challenge since there is currently no clearly effective antimicrobial therapy for these infections. The combinatorial effects of interferon-gamma (IFN-γ) with gentamicin and/or vancomycin against a clinical isolate of drug-resistant Enterococcus faecalis, were evaluated in an in vitro system with human neutrophils. Following inoculation of cultures of human neutrophils with the organism, treatments were initiated immediately after the infection and the number of viable bacteria was determined at 12, 18 and 24 h. Antibiotics were applied at concentrations close to their clinically achievable serum trough and peak levels. Treatment with IFN-γ alone induced a maximal growth inhibition of up to 40% at a concentration of 100 U/ml. Addition of the cytokine to either therapeutic trough or peak concentrations of gentamicin and vancomycin, or a combination of both antimicrobials, was associated with a significant (P<0.01) enhancement of anti-enterococcal activity compared with the effects of the agents alone. Investigation of a potential underlying mechanism of anti-enterococcal action of IFN-γ reveals that it is, most probably, largely due to an activated secretion of the microbicidal reactive oxygen intermediates by neutrophils. The results of this study show that there is a possibility that IFN-γ could be a useful adjunct in the treatment of multidrug-resistant E. faecalis.