In-vitro bactericidal activity of quinupristin/dalfopristin alone and in combination against resistant strains of Enterococcus species and Staphylococcus aureus

Abstract

In-vitro activities of quinupristin/dalfopristin, a semisynthetic injectable streptogramin, and vancomycin were compared against multidrug-resistant Enterococcus faecium and Enterococcus faecalis, methicillin-susceptible Staphylococcus aureus ATCC 25923 and a methicillin-resistant S. aureus (MRSA). Combinations of quinupristin/dalfopristin and/or vancomycin with ofloxacin or gentamicin were evaluated using the chequerboard technique. The only synergy observed was that between quinupristin/dalfopristin plus vancomycin and quinupristin/dalfopristin plus gentamicin against E. faecium (FIC index < 0.5). Time-kill curves were performed over 24 h with an inoculum of 1 x 107 cfu/mL and clinically achievable concentrations of quinupristin/dalfopristin, vancomycin, ofloxacin and gentamicin (6, 30, 5 and 5 mg/L, respectively). In time-kill studies, combinations of quinupristin/dalfopristin plus vancomycin and quinupristin/dalfopristin plus gentamicin were additive, not synergic, against E. faecium and achieved 99.9% killing in 21.2 h and 19.6 h, respectively. None of the combination regimens suppressed the regrowth of E. faecalis. Quinupristin/dalfopristin combined with vancomycin demonstrated consistent synergy against ATCC 25923 and the MRSA, achieving 99.9% killing in 12.1 h and 11.9 h, respectively. Overall, quinupristin/dalfopristin alone demonstrated inhibitory activity against E. faecium, but not against E. faecalis, and bactericidal activity was achieved only with quinupristin/dalfopristin in combination with vancomycin or gentamicin against E. faecium. Quinupristin/dalfopristin plus vancomycin was the most potent and reliable combination against both strains of S. aureus in time-kill studies.