title: In vitro activity and post-antibiotic effect of quinupristin/dalfopristin (Synercid).
abstract: The in vitro activities of quinupristin/dalfopristin (Synercid), ampicillin, erythromycin, clarithromycin, vancomycin, teicoplanin, ciprofloxacin and tetracycline were examined and compared against 526 gram-positive bacteria. The minimal inhibitory concentrations (MICs) for quinupristin/dalfopristin against Staphylococcus aureus, including methicillin-resistant strains, were low (MIC(90) = 0.5 mg/l), and were comparable with those of vancomycin and teicoplanin. This compound was superior to the macrolides and highly active against Streptococcus pneumoniae (both penicillin-sensitive and penicillin-resistant strains), with MIC(90) = 2 mg/l. It was also active against other streptococci, with MIC(90) = 4 mg/l. However, this agent is less active against enterococci (MIC(90) = 32 mg/l). Quinupristin/dalfopristin showed high activity against gram-positive anaerobes, including Clostridium spp., Peptococcus spp. and Peptostreptococcus spp., with MIC(90) < or = 2 mg/l. Quinupristin/dalfopristin was also investigated for its post-antibiotic effect (PAE) and bactericidal kinetics against nine strains of gram-positive organisms, including staphylococci, enterococci and pneumococci. Exponentially growing (log phase) cultures were exposed to quinupristin/dalfopristin at 2 x MIC. Growth kinetics was evaluated using viable counting. The drug was uniformly bactericidal against pneumococci and staphylococci within 2 and 8 h of exposure, respectively. The killing activity against enterococci was weak; there was little or no reduction in bacterial count over 24 h of incubation. PAEs ranging from 2.13 to 3.28 h, 0.92 to 3.02 h and 1.89 to 7.07 h were produced on the tested pneumococci, staphylococci and enterococci, respectively. This study showed that quinupristin/dalfopristin is a promising agent active against gram-positive bacteria. The prolonged PAEs also suggest that the drug could be used intermittently at more widely spaced dosing intervals against gram-positive organisms.
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, PR China. lingt@mailserv.med.cuhk.edu.hk
authors.forename: T K
authors.initials: TK
authors.lastname: Ling
authors.forename: K S
authors.initials: KS
authors.lastname: Fung
authors.forename: A F
authors.initials: AF
authors.lastname: Cheng
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D014769:Virginiamycin / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin