ANTIMICROBIAL CHARACTERISTICS OF QUINUPRISTIN DALFOPRISTIN (SYNERCID(R) AT 30/70 RATIO) COMPARED TO ALTERNATIVE RATIOS FOR IN-VITRO TESTING/

Quinupristin/dalfopristin is a new streptogramin combination that occu rs at a natural ratio and formulation of 30:70. Rapid metabolism of th e dalfopristin component to RP 12536 in vivo puts in question the vali dity of in vitro test of spectrum with the parent combination. In stud ies of quinupristin with both dalfopristin and RP 12536, a wide range of unties (30:70, 50: 50, 70:301 were tested by reference MIC and MBC tests. No significant potency differences were observed between combin ation ratios or metabolic components when testing 256 bacterial strain s. Quinupristin/dalfopristin or quinupristin/RP 12536 remained active, by bactericidal action against many staphylococci and Streptococcus s sp. Enterococcus faecium strains were susceptible (MIC90, 2 mu g/ml; s tatic effect only) to the streptogramin, but E. faecalis, Pasteurella multocida, Pediococcus ssp., Haemophilus influenzae, and Bacteroides f ragilis were generally less susceptible (MIC90, greater than or equal to 8 mu g/ml). The log phase inoculum was preferred for MBC and kill-c urve tests with this combination. The 30:70 ratio in vitro susceptibil ity test of quinupristin/dalfopristin as used to date, seems to predic t the potency and spectrum of this streptogramin accurately and all cl inically 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-resistan t E. faecium that exhibit susceptibility in this investigation. (C) 19 97 Elsevier Science Inc.