Dalbavancin

Dalbavancin (INN, trade names Dalvance in the US and Xydalba in Europe) is a novel second-generation lipoglycopeptide antibiotic. It belongs to the same class as vancomycin, the most widely used and one of the few treatments available to patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin (INN, trade names Dalvance in the US and Xydalba in Europe) is a novel second-generation lipoglycopeptide antibiotic. It belongs to the same class as vancomycin, the most widely used and one of the few treatments available to patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin is a semisynthetic lipoglycopeptide that was designed to improve upon the natural glycopeptides currently available, vancomycin and teicoplanin. It possesses in vitro activity against a variety of Gram-positive pathogens including MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE). It is a once-weekly, two-dose antibiotic, the rights to which Actavis acquired when it bought Durata Therapeutics in 2014. The Food and Drug Administration approved dalbavancin in May 2014 for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by certain susceptible bacteria such as Staphylococcus aureus including methicillin-susceptible and methicillin-resistant strains of Streptococcus pyogenes, in intravenous dosage form. Dalbavancin is an antibiotic used to treat acute bacterial skin and skin structure infections (ABSSSI) in adults caused by susceptible Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). MRSA infections have become problematic in the community and in healthcare settings due to resistance to many available antibiotics. Because dalbavancin has demonstrated efficacy against MRSA and other microorganisms to treat serious or life-threatening infections, it was the first drug approved as a Qualified Infectious Disease Product under the Generating Antibiotic Incentives Now (GAIN) act, which is part of the FDA Safety and Innovation Act. It has strong activity against many Gram-positive bacteria, including methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus. Based on MIC data and other studies, dalbavancin is more potent and bactericidal and therefore requires lower concentrations than vancomycin against these organisms. Dalbavancin also shows in vitro activity against vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. Other Gram-positive organisms belonging to the Bacillus spp., Listeria spp., and Corynebacterium spp. may show in vitro susceptibility, and dalbavancin may exhibit activity against enterococci expressing the VanB or VanC phenotype of acquired resistance against vancomycin. There is no clinically significant activity against Gram-negative bacteria. Two trials, DISCOVER 1 and DISCOVER 2, demonstrated noninferiority of dalbavancin compared to vancomycin/linezolid in the treatment of ABSSSI. Patients were randomly assigned to receive two doses of dalbavancin on days 1 and 8, or to receive intravenous vancomyin for at least 3 days with the option of switching to oral linezolid to complete 10 to 14 days of therapy. Investigators assessed the cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours as the primary endpoint and found that once-weekly dalbavancin was as effective as twice-daily intravenous vancomycin followed by oral linezolid. This once-weekly dosing regimen may offer an advantageous treatment option compared to daily or twice-daily dosing. Dalbavancin is contraindicated in patients with hypersensitivity to dalbavancin, such as skin reactions or anaphylaxis, and caution is advised for patients with known hypersensitivity to other glycopeptides. There is currently no data on cross-reactivity between dalbavancin and vancomyin. The most common adverse reactions encountered in Phase II and Phase III trials were nausea (5.5%), headache (4.7%), and diarrhea (4.4%), as well as rash (2.7%) and itchiness (2.1%). Other less frequent but serious adverse reactions included hematologic disorders, hepatotoxicity, Clostridium difficile colitis, bronchospasm, infusion-related reactions including Red Man Syndrome, and anaphylactic shock. In trials, dalbavancin was associated with higher rates of hemorrhagic events compared to comparator groups and should be a precaution in patients undergoing surgery or taking anticoagulants. Patients on dalbavancin also had post-baseline alanine aminotransferase (ALT) levels that were 3 times the upper normal limit, some even having elevations 10 times the upper normal limit; however, eight of the twelve dalbavancin-treated patients had comorbid conditions that could affect their ALT, compared to only one patient in the comparator group. There is no evidence of ototoxicity associated with dalbavancin.