Synergy study of vancomycin or teicoplanin plus gentamicin against enterococci, Staphylococcus aureus and coagulase-negative staphylococci by time-kill method.

ABSTRACT

We conducted a time-kill study comparing the combination of vancomycin plus gentamicin versus teicoplanin plus gentamicin against 20 clinical isolates each, of enterococci, S. aureus and coagulase-negative staphylococci. The concentrations of vancomycin and teicoplanin were selected so that cultures containing these drugs alone contained 10(3) to 10(6) cfu/ml after 24 hr, mostly 2 to 4 times the MIC for each isolate. In this way we could be certain that synergism or antagonism would not go undetected. One-fourth of the gentamicin MIC for each isolate was used throughout the study. In vitro bactericidal synergy was considered to be present when vancomycin plus gentamicin or teicoplanin plus gentamicin yielded at least a 2 log 10 decline in cfu/ml compared to vancomycin or teicoplanin alone. There was no significant difference between the two antibiotic combinations against these gram-positive cocci. The antibiotic combinations showed synergy against 75 per cent of enterococcal isolates, 70 per cent of S. aureus isolates and 50 per cent of coagulase-negative staphylococcal isolates when measured at 24 hr of incubation. Five (25%) enterococcal strains resistant to the synergistic effect of the antibiotic combinations had gentamicin MICs greater than 64 mg/L. For staphylococcal isolates, no association was found between synergy and gentamicin susceptibility, methicillin resistance, or tolerance to vancomycin or teicoplanin.