Showing papers on "Dalfopristin published in 1995"
TL;DR: RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum.
Abstract: RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against erythromycin-susceptible and -resistant gram-positive pathogens. The present experiments compared the therapeutic efficacy of RP 59500 with that of vancomycin against experimental endocarditis due to either of two erythromycin-susceptible or two constitutively erythromycin-resistant isolates of methicillin-resistant Staphylococcus aureus. RP 59500 had low MICs for the four test organisms as well as for 24 additional isolates (the MIC at which 90% of the isolates were inhibited was or = 6 h for quinupristin), since successful treatment was restored by artificially prolonging the dalfopristin levels for 6 h. Thus, RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum. This observation is also relevant to humans, in whom the life span of dalfopristin in serum is also shorter than that of quinupristin.
69 citations
TL;DR: Clinical evidence to date indicates that quinupristin/dalfopristin may be effective for the treatment of multidrug-resistant infections, especially those due to vancomycin-resistant enterococci and methicillin-resistant staphylococci.
Abstract: In recent years, the prevalence of multiple drug-resistant strains of common Gram-positive pathogens has grown in many regions of the world. Increasingly, methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, vancomycin-resistant enterococci, and penicillin-resistant pneumococci have been identified as causative organisms in serious and life-threatening infections. This increase in resistance highlights the need for new antimicrobial agents to expand the therapeutic armamentarium. Quinupristin/dalfopristin is the first of a unique class of antibiotics called streptogramins. It is characterized by a unique mechanism of action, intracellular activity, synergistic activity of its components, broad spectrum of activity against most Gram-positive cocci, common respiratory pathogens, and anaerobes, and demonstrated postantibiotic effect. Clinical evidence to date indicates that quinupristin/dalfopristin may be effective for the treatment of multidrug-resistant infections, especially those due to vancomycin-resistant enterococci and methicillin-resistant staphylococci. This article reviews the pharmacology, microbiology, and clinical experience with quinupristin/dalfopristin to date.
67 citations
TL;DR: Based on in vitro susceptibility testing, in vivo studies, and preliminary clinical data, RP 59500 may be an alternative to the glycopeptides, especially for inherently resistant organisms.
Abstract: Objective:To review the current knowledge on RP 59500 (quinupristin/dalfopristin, Synercid), a new streptogramin antibiotic, with respect to its pharmacology, pharmacokinetics, pharmacodynamics, mechanism of resistance, and in vitro inhibitory and bactericidal activity.Data Sources:A MEDLINE search using the keywords RP 59500, pristinamycin, virginiamycin, and streptogramin was performed. Relevant abstracts presented at recent scientific conferences also were consulted.Study Selection:Because RP 59500 is a relatively new investigational agent, relevant in vitro and animal studies were selected. All available human studies were included as well.Data Extraction:Data from in vitro and in vivo studies were included, with particular emphasis on human studies.Data Synthesis:RP 59500 is a new injectable streptogramin antibiotic consisting of a mixture of 2 synergistic pristinamycin compounds. RP 59500 possesses in vitro inhibitory and bactericidal activity against most isolates of gram-positive organisms includi...
49 citations
TL;DR: In time-kill studies the drug was rapidly bactericidal against S. pneumoniae but failed to kill most enterococci, even in the presence of gentamicin or human serum.
42 citations
TL;DR: In the fibrin clot model, RP 59500 was more effective than vancomycin in reducing organism titers over 72 h and the most optimal therapy was the combination regimen.
Abstract: The bactericidal activity and emergence of resistance to RP 59500 (quinupristin/dalfopristin) when it was administered alone and in combination with vancomycin against fibrin clots that have been infected with methicillin-susceptible Staphylococcus aureus ATCC 25923 or methicillin-resistant S. aureus (MRSA) 67 were evaluated in an in vitro pharmacodynamic infected fibrin clot model. Fibrin clots were infected with S. aureus to achieve an inoculum of approximately 10(9) CFU/g. Antibiotics were administered to simulate pharmacokinetics in humans: RP 59500 (7.5 mg/kg of body weight) every 8 h and vancomycin (15 mg/kg) every 12 h over 72 h. Preliminary test tube time-kill experiments with an inoculum of approximately 10(5) CFU/ml suggested that RP 59500 was more rapid in achieving a 99.9% reduction in the number of CFU per milliliter than vancomycin against ATCC 25923 (6.94 versus 24 h; P = 0.0003) and MRSA 67 (6.77 versus 17.03 h; P = 0.004). At a higher inoculum (approximately 10(8) CFU/ml), 99.9% kill was achieved only with the combination regimen against ATCC 25923 and MRSA 67 (10.9 and 10.5 h, respectively), with total reductions of 6.35 and 6.33 log10 CFU/ml over 24 h, respectively. In the fibrin clot model, RP 59500 was more effective than vancomycin in reducing organism titers over 72 h. In the fibrin clot model, the most optimal therapy was the combination regimen.
41 citations
TL;DR: The results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci and suggest it might advantageously replace some of the older prophylactic regimens.
Abstract: RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacteria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-susceptible streptococcal isolates or their constitutively erythromycin-resistant Tn916 delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bactericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 prophylaxis successfully prevented endocarditis due to both the erythromycin-susceptible parent strains and their erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals challenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standard macrolidelincosamide-streptogramin antibiotics used for endocarditis prophylaxis in humans. An oral form of RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed.
10 citations