Telavancin Versus Vancomycin for the Treatment of Complicated Skin and Skin‐Structure Infections Caused by Gram‐Positive Organisms

Stryjewski, Martín E.; Graham, Donald R.; Wilson, Samuel E.; O’Riordan, William; Young, David M.; Lentnek, Arnold; Ross, Douglas Patrick; Fowler, Vance G.; Hopkins, Alan R.; Friedland, H. David; Barriere, Steven L.; Kitt, Michael M.; Corey, G. Ralph; Study, Skin-Structure Infections

doi:10.1086/587896

Cited by 278 publications

(236 citation statements)

References 27 publications

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“…[9][10][11][12]14,[63][64][65][66][67][68][69][70][71][72][73] Vancomycin is effective and often used against MRSA cSSTIs in the hospital. Empiric therapy with vancomycin has increased from 2000 (18%) to 2006 (93%).…”

Section: Treatment Failurementioning

confidence: 99%

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Amin

Cerceo

Deitelzweig

et al. 2014

Mayo Clinic Proceedings

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The prevalence of skin and soft tissue infections (SSTIs) has been increasing in the United States. These infections are associated with an increase in hospital admissions. Hospitalists play an increasingly important role in the management of these infections and need to use hospital resources efficiently and effectively. When available, observation units are useful for treating low-risk patients who do not require hospital admission. Imaging tools may help to exclude abscesses and necrotizing soft tissue infections; however, surgical exploration remains the principal means of diagnosing necrotizing soft tissue infections. The most common pathogens that cause SSTIs are streptococci and Staphylococcus aureus. Methicillin-resistant S aureus (MRSA) is a prevalent pathogen, and concerns are increasing regarding the unclear distinctions between community-acquired and hospital-acquired MRSA. Other less frequent pathogens that cause SSTIs include Enterococcus species, Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa. Cephalexin and clindamycin are suitable options for infections caused by streptococcal species and methicillin-susceptible S aureus. The increasing resistance of S aureus and Streptococcus pyogenes to erythromycin limits its use in these infections, and better alternatives are available. Parenteral cefazolin, nafcillin, or oxacillin can be used in hospitalized patients with nonpurulent cellulitis caused by streptococci and methicillin-susceptible S aureus. When oral MRSA therapy is indicated, clindamycin, doxycycline, trimethoprim-sulfamethoxazole, or linezolid is appropriate. Vancomycin, linezolid, daptomycin, tigecycline, telavancin, and ceftaroline fosamil are intravenous options that should be used in MRSA infections that require patient hospitalization. In the treatment of patients with SSTIs, hospitalists are at the forefront of providing proper patient care that reduces hospital costs, duration of therapy, and therapeutic failures. This review updates guidelines on the management of SSTIs with a focus on infections caused by S aureus, particularly MRSA, and outlines the role of the hospitalist in the effective management of SSTIs.

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Section: Treatment Failurementioning

confidence: 99%

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Amin

Cerceo

Deitelzweig

et al. 2014

Mayo Clinic Proceedings

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“…1), a novel lipoglycopeptide antibiotic with a unique, multifunctional mechanism of action and rapid, concentration-dependent bactericidal activity, has completed two Phase III trials for complicated skin and skin structure infections, and is currently under evaluation for the treatment of hospital-acquired pneumonia [7]. Unlike vancomycin and teicoplanin, telavancin disrupts bacterial cell membrane integrity in addition to inhibiting peptidoglycan synthesis [8].…”

mentioning

confidence: 99%

In Vitro Antimicrobial Activity of Telavancin against Methicillin-resistant Staphylococcus aureus Clinical Isolates from Japan (2006)

et al. 2007

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In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 m g/ml to 0.5 m g/ml and a MIC 90 value of 0.5 mg/ml. The MIC 90 s of vancomycin and linezolid were 1.0m g/ml and 2 m g/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.Keywords telavancin, S. aureus, MRSA, surveillance, vancomycin, Japan, lipoglycopeptideThe global emergence of severe infections caused by Gram-positive pathogens with resistance or reduced susceptibility to antibiotics has become a major public health concern. Importantly, among Staphylococcus aureus isolates, the frequency with which methicillin-resistant strains (MRSA) are isolated is rising [1]. In addition, MRSA strains with reduced susceptibility to vancomycin, teicoplanin and linezolid are reported with increasing frequency [2ϳ4]. Failure of vancomycin to effectively treat serious staphylococcal infections has been reported and many experts believe that this may be due to its limited bactericidal activity [5,6].Telavancin (Fig. 1), a novel lipoglycopeptide antibiotic with a unique, multifunctional mechanism of action and rapid, concentration-dependent bactericidal activity, has completed two Phase III trials for complicated skin and skin structure infections, and is currently under evaluation for the treatment of hospital-acquired pneumonia [7]. Unlike vancomycin and teicoplanin, telavancin disrupts bacterial cell membrane integrity in addition to inhibiting peptidoglycan synthesis [8]. This dual mechanism of action may be the reason for the potent bactericidal activity observed with telavancin, which may also be a factor in limiting the emergence of resistance

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“…In patients from phase III trials, however, 1.5 % of those patients treated with telavancin for skin infections (vs. 0.6 % of vancomycin-treated patients) and 8 % of those treated for pneumonia (vs. 7 % with vancomycin) experienced QTc interval prolongation of [60 ms or a QTc interval [500 ms, the risk being higher when coadministered with drugs known to prolong the QTc interval or to induce torsades de pointes [10,140,156]. For oritavancin, two adverse reactions were more frequent than in the comparator-treated population [157].…”

Section: Adverse Eventsmentioning

confidence: 99%

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

Bambeke

2015

Drugs

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Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Grampositive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospitalacquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections. Key PointsNew lipoglycopeptides (telavancin, oritavancin, dalbavancin) differ from vancomycin by the presence of a lipophilic side chain, which profoundly modifies their pharmacokinetic and/or pharmacodynamic profile.Among these agents, telavancin and oritavancin have multiple modes of action and are highly bactericidal.Oritavancin and dalbavancin have prolonged halflives, allowing for their use a single-dose or twodose (once-a-week) regimen, respectively. These three drugs are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin is indicated for hospital-acquired and ventilator-associated bacterial pneumonia.

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Telavancin Versus Vancomycin for the Treatment of Complicated Skin and Skin‐Structure Infections Caused by Gram‐Positive Organisms

Abstract: Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.

Cited by 278 publications

References 27 publications

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

In Vitro Antimicrobial Activity of Telavancin against Methicillin-resistant Staphylococcus aureus Clinical Isolates from Japan (2006)

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

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