Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection

Abstract

In the era of increasing antibiotic resistance, development of new agents that could provide therapeutic options for difficult to treat pathogens is vital. Dalbavancin is a new lipoglycopeptide recently approved by the US FDA for the treatment of acute bacterial skin and skin structure infections. A derivative of the older glycopeptide class, chemical structure alterations resulted in a molecule with a similar mechanism of action, however, with a comparatively increased activity as reflected by organism MICs. These modifications also resulted in an antibiotic with distinctive properties that allow for once-weekly dosing in the treatment of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and drug resistant Streptococcus spp. As the first of these long acting compounds, understanding the pharmacokinetic and pharmacodynamic properties of agents like dalbavancin is essential for determining a place in therapy.

Clinical efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI)

“… 18 , 21 – 23 Since the clinical application of dalbavancin has not been established against these organisms not listed in the FDA approval, susceptibility breakpoints have not been established, but the susceptibilities based on in vitro testing appear similar to those listed in the dalbavancin prescribing information. As summarized by Leuthner et al, 24 the MIC range for many Gram-positive organisms including Streptococcus pneumoniae , and Viridans group Streptococcus spp. are between <0.03 and 0.25 µg/mL, suggesting that dalbavancin might be successful at treating infections caused by these pathogens.…”

Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance

“…Such clinically relevant lipoglycopeptide derivatives include the second-generation agents dalbavancin (BI-387) and oritavancin (LY-333328), and the third-generation agent telavancin (TD-6424) Pace et al 2003;Zhanel et al 2010;Karlowsky et al 2015;Leuthener et al 2015). Dalbavancin is derived structurally from teicoplanin; the addition of an extended, lipophilic side-chain results in enhanced potency and an extended halflife, whereas an amidated carboxyl side group results in enhanced antistaphylococcal activity ( Fig.…”