The Function of Dalbavancin in Acute Bacterial Skin and Skin Tissue Infections (ABSSSI)
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The Function of Dalbavancin in Acute Bacterial Skin and Skin Tissue Infections (ABSSSI)

2018-08-18

Introduction 

Dalbavancin, marketed under the brand name of Dalvance, is a new semi-synthetic glycopeptide antibiotic for antibacterial treatment of complex infections and infections caused by multi-drug resistant bacteria. It is an intravenous drug with excellence in vivo antibacterial activity and safety. Dalbavancin consists of five components A1, A2, B0, B1, and B2 with the same mother nucleus, of which B0 is the main component and B0 free base is doxycycline.

 Molecular structure of dalbavancin (Liu et al. 2014)

Figure 1: Molecular structure of dalbavancin (Liu et al. 2014)

Pharmacologic Action

Dalbavancin inhibits the biosynthesis of the cell wall of Gram-positive (G+) bacteria and is widely used as a drug for the treatment of skin and soft tissue infections. In vitro and in vivo tests have shown that dalbavancin has antibacterial activity against G+ bacteria including methicillin -resistant staphylococcus aureus (MRSA), methicillin-sensitive staphylococcus aureus (MSSA), coagulase-negative staphylococcus (CoNS), streptococci, etc. It is active against G+ pathogens including penicillin and ceftriaxone pneumoniae, teicoplanin-insensitive CoNS, non -van A type enterococci, and also active against G+ anaerobic bacteria. Its bactericidal mechanism is that dalbavancin binds to aminoacyl-D-alanyl-D-alanine at the end of the cell wall peptidoglycan precursor at the cleavage stage to suppress the synthesis of cell walls, thereby inhibiting and killing bacteria, and its lipophilic side chain extends into the bacterial cell membrane, increasing its stability and affinity.

Function

Dalbavancin is better tolerated and has a lower incidence of adverse reactions than the commonly used linezolid, with a 25.4% incidence of gastrointestinal symptoms for the most common adverse events, and the efficacy of dalbavancin and linezolid was similar. A dalbavancin phase 2 clinical trial using a single-dose group of 1100m g, two doses of 100 mg, 50 mg after 1 week, and a standard treatment group for comparative analysis showed that all treatment doses were well tolerated. The incidence of adverse reactions was similar in the three groups, and most of them were mild to moderate, and there was no significant change in biochemical or blood parameters. In a randomized, double-blind, double-dummy, multi-center, and non-inferior phase III clinical trial, the clinical effective rate of dalbavancin was 88.9%, and the recurrence rate after 1 month was less than 1.0%. The clinical efficacy of Staphylococcus aureus (including MRSA) is > 85%.

Pharmacokinetics and Metabolism

Dalbavancin is not a substrate, inhibitor, and inducer of the cytochrome P450 enzyme, thus it is less likely to interact with drugs metabolized by the P450 enzyme. Healthy subjects received 1 000 mg of dalbavancin in a single dose, 33% of the dose in 42 days was excreted in urine by the original form, 12% was excreted in the urine by the metabolite hydroxy dalbavancin, and the dose was taken within 70 days. 20% is excreted in the feces. The clearance rate is 0. 051 3 L·h-1 , and the half-life is 346 h.

References:

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3. Ciabatti R, Malabarba A. Semisynthetic glycope-ptides: chemistry, structure-activity relationships and prospects[J]. Farmaco, 1997, 52(5): 313-321.

4. Buckwalter M, Dowell JA. Population pharmacokinetic analysis of dalbavancin, a novel lipoglycopeptide. J ClinPharmacol. 2005, 45(11), 1279-1287.

5. Liu pengpeng. Dalbavancin [J]. Chinese Journal of Medicinal Chemistry, 2014,24(6): 122.

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