Time kill curve analysis of vancomycin and rifampin alone and in combination against nine strains of nutritionally deficient streptococci

Abstract

Endocarditis caused by nutritionally deficient streptococci has a high bacteriologic and clinical failure rate, despite appropriate antimicrobial therapy. We investigated by time kill curve methodology nine clinical endocarditis isolates of nutritionally deficient streptococci to determine the in vitro efficacies of vancomycin and rifampin alone and in combination. The combination of vancomycin and rifampin demonstrated synergy and bactericidal activity in five of the strains. In one strain, this combination inhibited growth by greater than 2 log10 CFU/ml when compared to the growth control or either antibiotic alone, but it failed to be bactericidal. Indifference, defined as less than or equal to 2 log10 CFU per milliliter increase in killing of the combination compared to the next most active single agent, was demonstrated with the remaining three isolates. Changing the antibiotic concentrations in the time kill curve studies for these latter strains failed to demonstrate synergistic activity of the antibiotic combination. The vancomycin and rifampin combination may be a promising therapeutic modality for which in vivo correlation is indicated.