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New Lipoglycopeptides

A Comparative Review of Dalbavancin, Oritavancin and Telavancin

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An Erratum to this article was published on 01 March 2011

Abstract

Dalbavancin, oritavancin and telavancin are semisynthetic lipoglycopeptides that demonstrate promise for the treatment of patients with infections caused by multi-drug-resistant Gram-positive pathogens. Each of these agents contains a heptapeptide core, common to all glycopeptides, which enables them to inhibit transglycosylation and transpeptidation (cell wall synthesis). Modifications to the heptapeptide core result in different in vitro activities for the three semisynthetic lipoglycopeptides. All three lipoglycopeptides contain lipophilic side chains, which prolong their half-life, help to anchor the agents to the cell membrane and increase their activity against Gram-positive cocci. In addition to inhibiting cell wall synthesis, telavancin and oritavancin are also able to disrupt bacterial membrane integrity and increase membrane permeability; oritavancin also inhibits RNA synthesis. Enterococci exhibiting the VanA phenotype (resistance to both vancomycin and teicoplanin) are resistant to both dalbavancin and telavancin, while oritavancin retains activity. Dalbavancin, oritavancin and telavancin exhibit activity against VanB vancomycin-resistant enterococci. All three lipoglycopeptides demonstrate potent in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis regardless of their susceptibility to meticillin, as well as Streptococcus spp. Both dalbavancin and telavancin are active against vancomycin-intermediate S. aureus (VISA), but display poor activity versus vancomycin-resistant S. aureus (VRSA). Oritavancin is active against both VISA and VRSA. Telavancin displays greater activity against Clostridium spp. than dalbavancin, oritavancin or vancomycin.

The half-life of dalbavancin ranges from 147 to 258 hours, which allows for once-weekly dosing, the half-life of oritavancin of 393 hours may allow for one dose per treatment course, while telavancin requires daily administration. Dalbavancin and telavancin exhibit concentration-dependent activity and AUC/MIC (area under the concentration-time curve to minimum inhibitory concentration ratio) is the pharmacodynamic parameter that best describes their activities. Oritavancin’s activity is also considered concentration-dependent in vitro, while in vivo its activity has been described by both concentration and time-dependent models; however, AUC/MIC is the pharmacodynamic parameter that best describes its activity.

Clinical trials involving patients with complicated skin and skin structure infections (cSSSIs) have demonstrated that all three agents are as efficacious as comparators. The most common adverse effects reported with dalbavancin use included nausea, diarrhoea and constipation, while injection site reactions, fever and diarrhoea were commonly observed with oritavancin therapy. Patients administered telavancin frequently reported nausea, taste disturbance and insomnia. To date, no drug-drug interactions have been identified for dalbavancin, oritavancin or telavancin. All three of these agents are promising alternatives for the treatment of cSSSIs in cases where more economical options such as vancomycin have been ineffective, in cases of reduced vancomycin susceptibility or resistance, or where vancomycin use has been associated with adverse events.

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No sources of funding were used to assist in the preparation of this review. The authors have declared that they have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    George G. Zhanel, Divna Calic, Frank Schweizer, Heather Adam, Philippe R. S. Lagacé-Wiens, Ethan Rubinstein, Alfred S. Gin, Daryl J. Hoban & James A. Karlowsky

  2. Department of Medicine, MS 673 Microbiology, Health Sciences Centre, 820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada

    George G. Zhanel & Ethan Rubinstein

  3. Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada

    Divna Calic, Sheryl Zelenitsky & Alfred S. Gin

  4. Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada

    Frank Schweizer

  5. Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba, Canada

    Heather Adam, Philippe R. S. Lagacé-Wiens, Daryl J. Hoban & James A. Karlowsky

  6. Department of Pharmacy, Health Sciences Centre, Winnipeg, Manitoba, Canada

    Alfred S. Gin

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  1. George G. Zhanel
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An Erratum for this chapter can be found at http://dx.doi.org/0012-6667/11/0005-0526/

An erratum to this article is available at http://dx.doi.org/10.2165/11591910-000000000-00000.

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Zhanel, G.G., Calic, D., Schweizer, F. et al. New Lipoglycopeptides. Drugs 70, 859–886 (2010). https://doi.org/10.2165/11534440-000000000-00000

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