ANTIBACTERIAL ACTIVITY OF QUINUPRISTIN DALFOPRISTIN - RATIONALE FOR CLINICAL USE

Most Gram-positive organisms are highly susceptible to the streptogram in, quinupristin/dalfopristin (RP 59500; Synercid(R)). Minimum inhibit ory concentrations for 90% of isolates (MIC(90)) were less than or equ al to 1 mg/L for Staphylococcus aureus, S. epidermidis, S. haemolyticu s, Streptococcus pneumoniae, S. pyogenes and Listeria monocytogenes. I mportantly, quinupristin/dalfopristin shows similar activity against m ethicillin-susceptible and -resistant strains of S. aureus, and strept ococci with benzylpenicillin (penicillin G)- or erythromycin-acquired resistance. Enterococci have varying susceptibility to quinupristin/ d alfopristin, although most isolates tested are susceptible to the drug , including a vancomycin-resistant and multiresistant Enterococcus fae cium. E. faecalis are generally the least susceptible. Among the Gram- negative respiratory pathogens Moraxella catarrhalis is susceptible an d Haemophilus influenzae is moderately susceptible to quinupristin/ da lfopristin; however, Enterobacteriaceae, Pseudomonas aeruginosa and Ac inetobacter spp. are resistant. The drug is active against anaerobic o rganisms tested, including Clostridium perfringens, Lactobacillus spp. , Bacteroides fragilis and Peptostreptococcus. Synergy has been demons trated in vancomycin-resistant and multiresistant E. faecium, and meth icillin-sensitive and -resistant S. aureus with the combination of van comycin and quinupristin/ dalfopristin. Quinupristin/dalfopristin show s antibacterial activity in vivo in animal models of infection, includ ing methicillin-sensitive and -resistant S. aureus infection in rabbit s, S. aureus and S, pneumoniae in mice, and erythromycin-sensitive and -resistant viridans group streptococci infections in rats. The drug i s rapidly bactericidal against Gram-positive organisms (with the excep tion of enterococci) at concentrations similar to or within 4-fold of the MIC, and it has a long postantibiotic effect both in vitro and in vivo.