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Published on: September 9, 2015
Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections
Jordan R Smith1, Karrine D Roberts2, Michael J Rybak3
1High Point University School of Pharmacy, 833 Montlieu Avenue, High Point, NC, 27265, USA.
Abstract:
Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). It is active against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and minimum inhibitory concentrations (MICs) are consistently <0.125 µg/ml, much lower than most other anti-MRSA agents. Dalbavancin possesses an extended half-life of over 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. It is approximately 95% protein bound and is widely distributed throughout the body, achieving concentrations similar to plasma levels in numerous tissues. Against MRSA, dalbavancin is 4-8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin such as hVISA and VISA. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against vancomycin-resistant enterococci is lacking. In phase 3 ABSSSI studies, dalbavancin demonstrated similar activity to vancomycin and provides a more convenient dosing regimen. Limited phase 2 data suggest dalbavancin also possesses activity in catheter-related bloodstream infections. Potential further therapeutic uses include conditions that require long-term treatment such as osteomyelitis and infective endocarditis, although data are currently lacking. The extended half-life of dalbavancin, along with its in vitro activity against gram-positive organisms with reduced susceptibility to other anti-MRSA antibiotics, suggest it could have an exciting clinical role going forward.
Insights
Dalbavancin is a new antibiotic effective against Gram-positive bacteria, including MRSA. Its extended half-life allows for convenient dosing for acute bacterial skin infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Dalbavancin is a lipoglycopeptide antibiotic approved for acute bacterial skin and skin structure infections (ABSSSIs).
- It exhibits potent in vitro activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).
- Dalbavancin has a prolonged half-life, enabling a simplified dosing regimen.
Purpose of the Study:
- To review the efficacy and pharmacokinetic profile of dalbavancin for ABSSSIs.
- To compare dalbavancin's activity against MRSA and other Gram-positive organisms with existing agents.
- To explore potential future therapeutic applications of dalbavancin.
Main Methods:
- Review of in vitro studies assessing dalbavancin's minimum inhibitory concentrations (MICs).
- Analysis of Phase 3 clinical trial data comparing dalbavancin to vancomycin for ABSSSI treatment.
- Evaluation of pharmacokinetic data regarding dalbavancin's protein binding and tissue distribution.
- Assessment of limited Phase 2 data for catheter-related bloodstream infections.
Main Results:
- Dalbavancin demonstrates potent in vitro activity against MRSA (MICs <0.125 µg/ml), exceeding vancomycin's potency by 4-8 times.
- It shows activity against vancomycin-intermediate and -heterogeneous strains of Staphyloccocus aureus (VISA/hVISA).
- Phase 3 trials indicate dalbavancin has comparable efficacy to vancomycin for ABSSSI with a more convenient dosing schedule.
- Dalbavancin exhibits activity against streptococci and enterococci, but not vancomycin-resistant enterococci.
Conclusions:
- Dalbavancin offers a valuable therapeutic option for ABSSSIs due to its potent Gram-positive activity and extended half-life.
- Its favorable pharmacokinetic profile and in vitro potency suggest potential utility in other serious Gram-positive infections.
- Further research is warranted to establish dalbavancin's role in conditions like osteomyelitis and infective endocarditis.
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