Triple Combination Penicillin-Vancomycin-Gentamicin for Experimental Endocarditis Caused by a Highly Penicillin- and Glycopeptide-Resistant Isolate of Enterococcus faecium
A combination of low-dose penicillin (75,000 IV/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IV/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to β-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 εg/mL) and vancomycin (MIC, 512 εg/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killingcurve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.