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Antibacterial activity of quinupristin/dalfopristin. Rationale for clinical use.

Most Gram-positive organisms are highly susceptible to the streptogramin, quinupristin/dalfopristin (RP 59500; Synercid). Minimum inhibitory concentrations for 90% of isolates (MIC90) were < or = 1 mg/L for Staphylococcus aureus, S. epidermidis, S. haemolyticus, Streptococcus pneumoniae, S. pyogenes and Listeria monocytogenes. Importantly, quinupristin/dalfopristin shows similar activity against methicillin-susceptible and -resistant strains of S. aureus, and streptococci with benzylpenicillin (penicillin G)- or erythromycin-acquired resistance. Enterococci have varying susceptibility to quinupristin /dalfopristin, although most isolates tested are susceptible to the drug, including vancomycin-resistant and multiresistant Enterococcus faecium. E. faecalis are generally the least susceptible. Among the Gram-negative respiratory pathogens Moraxella catarrhalis is susceptible and Haemophilus influenzae is moderately susceptible to quinupristin/ dalfopristin; however, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. are resistant. The drug is active against anaerobic organisms tested, including Clostridium perfringens, Lactobacillus spp., Bacteroides fragilis and Peptostreptococcus. Synergy has been demonstrated in vancomycin-resistant and multiresistant E. faecium, and methicillin-sensitive and -resistant S. aureus with the combination of vancomycin and quinupristin/ dalfopristin. Quinupristin/dalfopristin shows antibacterial activity in vivo in animal models of infection, including methicillin-sensitive and -resistant S. aureus infection in rabbits, S. aureus and S. pneumoniae in mice, and erythromycin-sensitive and -resistant viridans group streptococci infections in rats. The drug is rapidly bactericidal against Gram-positive organisms (with the exception 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.