Dalfopristin

About: Dalfopristin is a research topic. Over the lifetime, 696 publications have been published within this topic receiving 26621 citations. The topic is also known as: RP-54476 & Dalfopristina.

What is the role of streptogramins in intensive care

Abstract: The combination of two injectable streptogramins, quinupristin/dalfopristin, provides a new pharmacological choice proven to be therapeutically efficacious against most Gram-positive, multi-resistant microorganisms. They have been shown to be efficacious above all in critically ill patients hospitalized in intensive care who have unique alterations in homeostasis that makes tissue penetration of various pharmacological antimicrobials difficult. In cases of infection localized in difficult-to-treat sites, the combination with other drugs, such as cefepime, a glycopeptide or linezolid, is able to potentiate the action of the streptogramin with positive results which allow resolution of the illness. In this article, we review data from the literature on the use of quinupristin/dalfopristin in the treatment of Gram-positive, multi-resistant infections in critically ill patients.

Susceptibility of Glycopeptide-Resistant Enterococci to Linezolid, Quinupristin/dalfopristin, Tigecycline and Daptomycin in a Tertiary Greek Hospital.

Abstract: We investigated the antibiotic susceptibility of glycopeptide-resistant enterococci (GRE). Seventy consecutive GRE were tested. Sixty-two isolates were identified as Enterococcus faecium (88.6%), and 8 (11.4%) as Enterococcus faecalis. All strains were susceptible to linezolid and daptomycin, while 17.1% (12/70) and 11.4% (8/70) were resistant to quinupristin/dalfopristin (QD) and tigecycline, respectively. All E. faecalis isolates were resistant to QD, while 4 of 62 (6.5%) E. faecium isolates were resistant to QD. All E. faecalis isolates were susceptible to tigecycline, while 14.5% (9/62) E. faecium isolates were resistant. Continued surveillance of GRE antibiotic susceptibilities is important for combating these multi-resistant nosocomial pathogens.

First report of clinical linezolid-resistant Staphylococcus cohnii mediated by the cfr gene

Abstract: cfr (chloramphenicol-florfenicol resistance) gene, initially associated with chloramphenicol resistance, represents an additionally natural linezolid resistance mechanism, which could be transmitted between species. Coagulase-negative staphylococci may be a reservoir ofcfr gene and cfr-carrying isolates may become a serious threat to several potent Gram-positive-active agents. We isolated two linezolid-resistant Staphylococcus cohnii from clinical patients in China for the first time. Both isolates were carrying cfr gene and no G2576T mutation. They are resistant to quinolones, tetracycline, erythromycin, clindamycin, trimethoprim/sulfamethoxazole and chloramphenicol, and susceptible to vacomycin, teicoplanin, rifampicin, gentamicin, tigecycline, quinupristin/dalfopristin. The minimum inhibitory concentrations (MICs) of linezolid to each S. cohnii were more than 256 mg/L; the MICs of vancomycin were 2 mg/L. Our results raise concerns about the future clinical efficacy of several antimicrobial classes; effective measures, such as hygiene, separate and prospective resistance surveillance, should be taken to prevent cfr gene transmission. Key words: cfr (chloramphenicol-florfenicol resistance), resistance, Staphylococcus cohnii, linezolid.

New anti-Gram-positive agents.

Abstract: As the prevalence of resistant Gram-positive organisms in the critical care unit has increased, so have the associated morbidity and mortality and the cost of their treatment. As a result, more toxic and less active second-line agents and combinations of agents are used, often with limited evidence of clinical benefit. Although widely used, the role of glycopeptides is limited by increasing resistance and poor pharmacokinetics. New agents now in use, such as quinupristin/dalfopristin and Linezolid (Zyvox; Pharmacia & Upjohn, Kalamazoo, MI), show promise, as do diverse agents in development. The future is likely to bring greater therapeutic choice but, inevitably, further resistance.

Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

Abstract: Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question of whether they have a combined effect on antibiotic resistance or growth. We transformed a plasmid-borne cfr gene into a uL3-depleted Escherichia coli strain containing either wild-type L3 or L3 with one of seven mutations, G147R, Q148F, N149S, N149D, N149R, Q150L, or T151P, expressed from plasmid-carried rplC genes. The L3 mutations are well tolerated, with small to moderate growth rate decreases. The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were seen. This study underscores the complex interplay between various resistance mechanisms and cross-resistance, even from antibiotics with overlapping binding sites.