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Journal of Antimicrobial Chemotherapy, Vol 39, 33-39, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy

ORIGINAL ARTICLES

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

SL Kang and MJ Rybak
School of Pharmacy, University of the Pacific, Santa Barbara, CA, USA. uoplena@aol.com

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 10(7) 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.
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