Antistaphylococcal Activities of Telavancin Tested Alone and in Combination by Time-Kill Assay

Lin, Gengrong; Pankuch, Glenn A.; Ednie, Lois M.; Appelbaum, Peter C.

doi:10.1128/aac.01143-09

Cited by 23 publications

(17 citation statements)

References 29 publications

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“…Synergy has been demonstrated in vitro between oritavancin and aminoglycosides, b-lactams, linezolid, or rifampin against MRSA or enterococci [90][91][92][93] as well as between telavancin and b-lactams, aminoglycosides, or rifampin against MRSA [94,95], or dalbavancin and oxacillin against MRSA [96].…”

Section: In Vitro Pharmacodynamicsmentioning

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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Section: In Vitro Pharmacodynamicsmentioning

confidence: 99%

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

Bambeke

2015

Drugs

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“…TLV was reported to have synergy when combined with all the examined antibiotics, but the highest synergy rates were observed at 24 h when subinhibitory concentrations of TLV were combined with clinically relevant, subinhibitory concentrations of gentamicin, ceftriaxone, meropenem and rifampicin [Lin et al 2010].…”

Section: Pharmacokinetics/pharmacodynamicsmentioning

confidence: 99%

Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilator-associated pneumonia: clinical evidence and experience

Liapikou

Dimakou

Toumbis

2016

Ther Adv Respir Dis

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Telavancin (TLV) is a lipoglycopeptide derivative of vancomycin (VAN), which has activity against Gram-positive aerobic bacteria, and is especially effective against methicillinresistant Staphylococcus aureus (MRSA) and Gram-positive bacteria resistant to VAN. Comparative clinical studies of TLV have demonstrated noninferiority compared with VAN in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for TLV-treated patients with monomicrobial S. aureus infection, including isolates with reduced VAN susceptibility. The results based on the patients' clinical response were supported by supplemental post-hoc analyses of 28-day mortality. In Europe and the USA, TLV is approved as a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. The present article reviews TLV's pharmacological characteristics and clinical efficacy resulting from clinical trials giving a detailed picture of its properties and position in the management of hospital-acquired pneumonia.

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“…Telavancin exerts concentration-dependent bactericidal activity against Gram-positive organisms [32,33]. Concentration-dependent bactericidal effects were demonstrated in time-kill studies against target organisms, including methicillin-sensitive S. aureus (MSSA), MRSA, VISA and coagulase-negative staphylococci.…”

Section: Bactericidal Activitymentioning

confidence: 99%

Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of Gram-positive infection

Hegde

Janc

2014

Expert Review of Anti-infective Therapy

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Antistaphylococcal Activities of Telavancin Tested Alone and in Combination by Time-Kill Assay

Cited by 23 publications

References 29 publications

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

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

Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilator-associated pneumonia: clinical evidence and experience

Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of Gram-positive infection

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