Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin

Evidence of synergism between combinations of vancomycin and beta-lactam an tibiotics against 59 isolates of methicillin-resistant staphylococci (Staph ylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolytic us) for which vancomycin MICs ranged from 1 to 16 mu g/ml were tested by br oth microdilution checkerboard, disk diffusion, agar dilution, and time-kil l antimicrobial susceptibility tests. The combination of vancomycin and oxa cillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxi cillin-clavulanate but not for aztreonam. Evidence of synergy correlated di rectly with vancomycin MICs, The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental e ndocarditis caused by three clinical isolates of glycopeptide-intermediate- susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in th is model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffectiv e for animals infected with HIP5827 or MU50, However, the combination of va ncomycin and nafcillin resulted in a mean reduction of 4.52 log(10) CFU/g o f aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4.15 log(10) CFU/g for animals infected with MU50, Renal abscesses caused by HIP5827 were sterili zed significantly better with the combination of vancomycin and nafcillin t han by either treatment alone. We conclude that the combination of vancomyc in and beta-lactams,vith antistaphylococcal activity is an effective regime n for the treatment of infections with clinical strains of staphylococci wh ich demonstrate reduced susceptibility to glycopeptides.