Efficacy of LY333328 against Experimental Methicillin-Resistant
            <i>Staphylococcus aureus</i>
            Endocarditis

Kaatz, Glenn W.; Seo, Susan M.; Aeschlimann, Jeffrey R.; Houlihan, Heather H.; Mercier, Renée-Claude; Rybak, Michael J.

doi:10.1128/aac.42.4.981

Cited by 58 publications

(28 citation statements)

References 14 publications

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“…The single HEQ dose of 1200 mg oritavancin was able to reduce S. aureus to undetectable levels in the blood and to reduce significantly the bacterial burden in the spleen. This efficacy correlates well with data from studies conducted in other bloodstream infection models [35,36,52] and supports further development of oritavancin's use to treat bacteraemia. In a hamster model of C. difficile infection, oritavancin was better than vancomycin at prolonging survival and preventing disease relapse [54].…”

Section: In Vivo Animal Studiessupporting

confidence: 83%

“…60%, 20%, 3%, 2% and 2-10% of the administered dose detected at each site, respectively [3,28,32,33]. Oritavancin penetrates bone [34] and cardiac vegetations [21,[35][36][37]. Entry into the cerebrospinal fluid amounts to 1-5% of the unbound plasma drug concentration [38].…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The use of oritavancin in several disease states has been evaluated in numerous animal models, including a rat model of catheter-related infection [52], two different rabbit models of meningitis [38,53], a rat model of MSSA and three rabbit models of MRSA and VRE endocarditis [21,[35][36][37]. In all these models, oritavancin eradicated infection when used alone or in combination with other agents.…”

Section: In Vivo Animal Studiesmentioning

confidence: 99%

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Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains

Bouza

Burillo

2010

International Journal of Antimicrobial Agents

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Oritavancin is a lipoglycopeptide antibiotic under investigation for the treatment of serious infections caused by Gram-positive bacteria. Oritavancin has demonstrated rapid dose-dependent bactericidal activity towards vancomycin-susceptible and -resistant enterococci, meticillin-susceptible and -resistant Staphylococcus aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), vancomycin-resistant S. aureus (VRSA) and small-colony variants of S. aureus. It is also active against Clostridium difficile. Upon intravenous administration, oritavancin displays a three-compartment pharmacokinetic model, dose proportionality, a distribution volume of ca. 110 L, a terminal elimination half-life in excess of 2 weeks and it is not metabolised. Its pharmacodynamic properties make it an ideal antibiotic for a once-daily or even single-dose regimen. Oritavancin is currently under review by the US Food and Drug Administration. So far, oritavancin has demonstrated efficacy in two pivotal Phase III trials conducted in patients with complicated skin and skin-structure infections in which oritavancin was compared with vancomycin plus cefalexin. In both trials, the primary endpoint (clinical cure in clinically evaluable patients at first follow-up with a 10% non-inferiority margin) was met, with the advantages of shorter duration of therapy and fewer adverse events. Further results indicating its activity against bacteria growing in biofilms as well as stationary-phase bacteria open the way for its use to treat prosthetic device infections, which is to be investigated in upcoming trials.

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Section: In Vivo Animal Studiessupporting

confidence: 83%

Section: Pharmacokineticsmentioning

confidence: 99%

Section: In Vivo Animal Studiesmentioning

confidence: 99%

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Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains

Bouza

Burillo

2010

International Journal of Antimicrobial Agents

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“…Recent autoradiography studies in experimental rabbit endocarditis indicate that LY333328 diffuses through cardiac vegetations similar to that of other glycopeptides [17]. Efficacy with LY333328 has been demonstrated in several animal models of S. aureus endocarditis [18]. However, there is limited data to date in this model for VREF.…”

Section: New Antibiotics With Activity Against Vancomycin-resistant Ementioning

confidence: 97%

Vancomycin-resistant Enterococcus: Infectious endocarditis treatment

Rybak

Coyle

1999

Curr Infect Dis Rep

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Vancomycin-resistant Enterococcus species represent serious gram-positive pathogens for which there is currently no recommended therapy. There are a number of new antibiotics with activity against these pathogens in development. Although there is a great deal of experience with some of these agents for skin and soft tissue infections, bacteremia, pneumonia, and intra-abdominal infections, there is currently little information available for the treatment of endocarditis. Animal and limited human data thus far suggest that new agents such as quinuprisitin-dalfopristin, LY333328 (a new glycopeptide antibiotic), and daptomycin (a lipopeptide antibiotic) may prove useful for this indication. Additional information, and especially combination treatment, are warranted to improve success and limit the emergence of resistance to these new antibiotics.

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“…[45][46][47] In animal studies that involved rabbits as models, oritavancin was successful in the treatment of endocarditis from MRSA. 48 It also has a longer half-life (Ͼ10 days) than vancomycin does and thus can potentially offer a shorter duration of treatment. 49 In a phase III study, intravenous oritavancin (either 1.5 mg/kg or 3.0 mg/kg once daily) followed by placebo was compared with intravenous vancomycin (15 mg/kg once daily) followed by oral cephalexin in 517 patients with complicated skin and soft-tissue infections.…”

Section: Oritavancinmentioning

confidence: 99%