Telavancin

Corey, G. Ralph; Stryjewski, Martín E.; Weyenberg, Wim; Yasothan, Uma; Kirkpatrick, Peter

doi:10.1038/nrd3051

Cited by 47 publications

(35 citation statements)

References 12 publications

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“…Vancomycin (15), teicoplanin (16), and three recently approved semisynthetic derivatives, oritavancin (17), dalbavancin (18), and telavancin (19), are widely used to treat refractory bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) (20). Vancomycin (1) (Fig.…”

mentioning

confidence: 99%

Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Okano

Isley

Boger

2017

Proc. Natl. Acad. Sci. U.S.A.

180

215

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Significance In a quest for antibiotics that may display durable clinical lifetimes, analogs of the glycopeptide antibiotics, including vancomycin, have been designed that not only directly overcome the molecular basis of existing vancomycin resistance but also contain two added peripheral modifications that endow them with two additional independent mechanisms of actions not found in the parent antibiotics. It is shown that such peripherally and binding pocket-modified vancomycin analogs display little propensity for acquired resistance by vancomycin-resistant Enterococci and that both their antimicrobial potency and durability against such challenges follow trends (three > two > one mechanisms of action) that are now predictable.

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mentioning

confidence: 99%

Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Okano

Isley

Boger

2017

Proc. Natl. Acad. Sci. U.S.A.

180

215

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“…In the phase III cSSSI study ATLAS I ( n = 855 patients), no differences in serious adverse events were noted between the telavancin and vancomycin groups (Corey et al 2009 ). The safety results of two pneumonia phase III studies (ATTAIN I and II, n = 1,506 patients), showed similar rates of adverse events in the telavancin and vancomycin groups (Rubinstein et al 2011 ) The most common adverse events with telavancin were similar to other studies.…”

Section: Toxicity Of Telavancinmentioning

confidence: 96%

Glycopeptides

Gyssens

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Glycopeptides are a class of antibiotic drugs that is composed of glycosylated cyclic or polycyclic nonribosomal peptides. Older molecules used in clinical practice are vancomycin and teicoplanin. Oritavancin, dalbavancin, and telavancin belong to the subclass of lipoglycopeptides. Glycopeptides inhibit bacterial cell wall peptoglycan synthesis of aerobic and anaerobic Gram-positive bacteria. Glyco (lipo)peptides are not absorbed orally and have to be administered intravenously. In this chapter, the pharmacokinetics (Pk) and the pharmacodynamics (Pd) of the glycopeptides are studied. Pk in serum as well as protein binding and elimination are reviewed. Pharmacodynamic data include MICs of Gram-positive bacteria, PK/Pd effects in in vitro systems, animal models and human studies. Adverse effects of glycopeptides on the host are concentration related nephro-and ototoxicity. In the past, because of fear of toxicity, the older glycopeptides have been underdosed in many settings. The implementation of Pk/Pd knowledge into clinical practice by e.g. administering higher doses of vancomycin and teicoplanin and using continuous infusion of vancomycin is urgently needed. This chapter contains clinical vignettes showing the benefi t of Therapeutic Drug Monitoring of glycopeptides.

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“…One of the most widely recognized peripheral modifications of glycopeptide antibiotics is the hydrophobic substitution of the vancosamine free amine first discovered at Eli Lilly and inspired by the lipophilic acyl groups found in teicoplanin. 190–192 To date, three semi-synthetic analogues; oritavancin ( 259 , 2014, The Medicines Company), 193 telavancin ( 260 , 2009, Theravance), 194,195 and dalbavancin ( 261 , 2014, Vicuron Pharmaceuticals Inc.) 196–198 that bear such substitution have been approved for clinical use (Figure 17). Importantly, the hydrophobic substituent enhances the antibiotic potency against both vancomycin sensitive and resistant pathogens.…”

Section: Total Syntheses Of Residue 4 Modified Vancomycins and Keymentioning

confidence: 99%

Total Syntheses of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues

2017

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A review of efforts that have provided total syntheses of vancomycin and related glycopeptide antibiotics, their agylcons, and key analogues is provided. It is a tribute to developments in organic chemistry and the field of organic synthesis that not only can molecules of this complexity be prepared today by total synthesis, but that such efforts can be extended to the preparation of previously inaccessible key analogues that contain deep-seated structural changes. With the increasing prevalence of acquired bacterial resistance to existing classes of antibiotics and with the emergence of vancomycin resistant pathogens (VRSA and VRE), the studies pave the way for the examination of synthetic analogues rationally designed to not only overcome vancomycin resistance, but to provide the foundation for the development of even more powerful and durable antibiotics.

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Telavancin

Cited by 47 publications

References 12 publications

Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Glycopeptides

Total Syntheses of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues

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Telavancin

Cited by 47 publications

References 12 publications

Peripheral modifications of [Ψ[CH 2 NH]Tpg 4 ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Peripheral modifications of [Ψ[CH 2 NH]Tpg 4 ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Glycopeptides

Total Syntheses of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues

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Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics

Peripheral modifications of [Ψ[CH ₂ NH]Tpg ⁴ ]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics