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Dalfopristin

About: Dalfopristin is a(n) research topic. Over the lifetime, 696 publication(s) have been published within this topic receiving 26621 citation(s). The topic is also known as: RP-54476 & Dalfopristina.


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Journal ArticleDOI
TL;DR: Few anti-staphylococcal agents were launched from 1970 to 1995, but the situation is now improving, and S. aureus is a resilient foe, able to regain its importance if drugs are used profligately or if hygiene is slackened.
Abstract: When penicillin was introduced in 1944 over 94% of Staphylococcus aureus isolates were susceptible; by 1950 half were resistant. By 1960 many hospitals had outbreaks of virulent multi-resistant S. aureus. These were overcome with penicillinase-stable penicillins, but victory was brief; methicillin-resistant S. aureus (MRSA) were recorded in the year of the drug's launch. MRSA owe their behaviour to an additional, penicillin-resistant peptidoglycan transpeptidase, PBP-2', encoded by mecA. Their spread is clonal, with transfer of mecA being extremely rare. MRSA accumulated and then declined in the 1960s and 1970s, but became re-established in the early 1980s. Some early MRSA strains were colonists rather than invaders and the proportion of MRSA among S. aureus bacteraemias in England remained under 3% until 1992. However, this proportion rose to 34-37% by 1998-1999, reflecting the dissemination of two new epidemic strains, EMRSA 15 and 16. These may be more virulent than earlier MRSA, or their success may reflect changing hospital practice. Until 1996, glycopeptides were universally active against S. aureus; then glycopeptide-intermediate S. aureus (GISA) were found in Japan, France, and the USA. This resistance is associated with increased wall synthesis. Coagulase-negative staphylococci (CNS) are less pathogenic than S. aureus but are important in line-associated bacteraemias and prosthetic device infections. They are even more often resistant than S. aureus, notably to teicoplanin. Few anti-staphylococcal agents were launched from 1970 to 1995, but the situation is now improving. Dalfopristin/quinupristin inhibits virtually all S. aureus, although its bactericidal activity is impaired against strains with constitutive MLSB-type resistance; other new agents are in advanced development. New agents give a renewed opportunity for control, but S. aureus is a resilient foe, able to regain its importance if drugs are used profligately or if hygiene is slackened.

425 citations

Journal ArticleDOI
TL;DR: Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin.
Abstract: The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

326 citations

Journal ArticleDOI
TL;DR: Clonal spread appears to be a dominant factor of MDR VRE dissemination on both continents, and further monitoring is critical to assist in the control of these resistant pathogens.
Abstract: Increases in prevalence of vancomycin-resistant enterococci (VRE) have been documented globally since its emergence in the 1980s. A SENTRY Antimicrobial Surveillance Program (2003) objective monitored VRE isolates with respect to antimicrobial susceptibility trends, geographic resistance variability, and clonal dissemination. In 2003, VRE isolates from North America (United States and Canada, n = 839, 26 sites) and Europe (n = 56, 10 sites) were susceptibility tested using Clinical and Laboratory Standards Institute (CLSI) reference methodologies. Based on resistance profiles, 155 isolates displayed similar multidrug-resistant (MDR) profiles and were temporally related; these were subsequently submitted for typing by pulsed-field gel electrophoresis (PFGE). Most of the submitted isolates were Enterococcus faecium (91.0%) and Enterococcus faecalis (7.8%). Among VRE, the VanA phenotype was more prevalent in North America (76%) than Europe (40%), and all isolates had elevated resistance rates to other antimicrobial classes including the following: 1) chloramphenicol resistance among E. faecalis being greater in North America than in Europe (28.6% versus 7.1%, respectively) but reversed among E. faecium (0.5% and 15.0%, the latter due to clonal occurrences); 2) ciprofloxacin resistance in North America >99% for both species and in Europe varying from 85.7% to 87.5%; 3) rare occurrences of linezolid resistance in North America (0.8% to 1.8%) due to G2576U ribosomal mutation; 4) higher quinupristin/dalfopristin resistance observed among European E. faecium strains (10.0% versus 0.6%); and 5) higher rifampin resistance rates among European E. faecalis (21.4% versus 5.4%). Thirty-five MDR epidemic clusters were identified by PFGE in 21 North American and 2 European medical centers including the following: 1) VanA (20 sites, 27 clonal occurrences) and VanB (1 site, 2 clonal occurrences); 2) elevated quinupristin/dalfopristin MIC results (not vatD/E, 3 sites); and 3) chloramphenicol resistance (chloramphenicol acetyltransferase-positive strains, 3 sites). The esp gene, part of the putative E. faecium pathogenicity island and a marker for the clonal complex-17 lineage, was detected in 76% of vancomycin-resistant E. faecium. Clonal spread appears to be a dominant factor of MDR VRE dissemination on both continents, and further monitoring is critical to assist in the control of these resistant pathogens.

321 citations

Journal ArticleDOI
TL;DR: Combined therapies and newer agents hold promise for the future treatment of vancomycin-resistant Enterococcus infections, but further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.
Abstract: Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

290 citations

Journal ArticleDOI
TL;DR: Finding of acquired resistance genes in isolates intended for probiotic or nutritional use highlights the importance of antimicrobial susceptibility testing in documenting the safety of commercial LAB.
Abstract: Results: Tentative ECOFF values of 13 antibiotics were determined for up to 12 LAB species. Generally, LAB were susceptible to penicillin, ampicillin, ampicillin/sulbactam, quinupristin/dalfopristin, chloramphenicol and linezolid. LAB exhibited broad or partly species-dependent MIC profiles of trimethoprim, trimethoprim/sulfamethoxazole, vancomycin, teicoplanin and fusidic acid. Three probiotic Lactobacillus strains were highly resistant to streptomycin. Although erythromycin, clindamycin and oxytetracycline possessed high antimicrobial activities, 17 Lactobacillus isolates were resistant to one or more of these antibiotics. Eight of them, including six probiotic and nutritional cultures, possessed erm(B) and/or tet(W), tet(M) or unidentified members of the tet(M) group. In vitro intra- and interspecies filter-mating experiments failed to show transfer of resistance determinants.

288 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20219
202010
201913
201811
201717
201612