Antimicrobial characteristics of quinupristin/dalfopristin (Synercid at 30:70 ratio) compared to alternative ratios for in vitro testing

Quinupristin/dalfopristin is a new streptogramin combination that occurs at a natural ratio and formulation of 30:70. Rapid metabolism of the dalfopristin component to RP 12536 in vivo puts in question the validity of in vitro test of spectrum with the parent combination. In studies of quinupristin with both dalfopristin and RP 12536, a wide range of ratios (30:70, 50:50, 70:30) were tested by reference MIC and MBC tests. No significant potency differences were observed between combination ratios or metabolic components when testing 256 bacterial strains. Quinupristin/dalfopristin or quinupristin/RP 12536 remained active, by bactericidal action against many staphylococci and Streptococcus ssp. Enterococcus faecium strains were susceptible (MIC90, 2 micrograms/ml; static effect only) to the streptogramin, but E. faecalis, Pasteurella multocida, Pediococcus ssp., Haemophilus influenzae, and Bacteroides fragilis were generally less susceptible (MIC90, > or = 8 micrograms/ml). The log phase inoculum was preferred for MBC and kill-curve tests with this combination. The 30:70 ratio in vitro susceptibility test of quinupristin/dalfopristin as used to date, seems to predict the potency and spectrum of this streptogramin accurately and all clinically important in vivo ratios of the injectable form or its major metabolites. Quinupristin/dalfopristin should be further investigated for clinical use against emerging resistant Gram-positive infections, especially penicillin-resistant streptococci and glycopeptide-resistant E. faecium that exhibit susceptibility in this investigation.