Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review

Abstract

Increasing rates of antimicrobial resistance among strains of Streptococcus, Staphylococcus, and Enterococcus spp. have been widely documented. At least 50% of nosocomial Staphylococcus aureus infections in intensive care units in the US and UK are due methicillin-resistant S. aureus (MRSA). Drug resistance is not confi ned to hospitals, and community-acquired MRSA (CA-MRSA) strains are now common causes of complicated skin and soft-tissue infections (cSSTIs) in many regions. Dalbavancin is a novel parenterally administered semisynthetic lipoglycopeptide similar to the naturally produced glycopeptides vancomycin and teicoplanin. Dalbavancin features a multifaceted mechanism of action that inhibits bacterial cell wall formation by two different mechanisms that enhances its activity against a wide range of gram-positive bacteria including staphylococci, streptococci, enterococci, and some anaerobes. Additionally, dalbavancin possesses unique pharmacokinetic properties, the most signifi cant of which is a long terminal half-life that allows for once weekly dosing. This attribute may prove to yield clinical and cost benefi t. Overall, clinical trials indicate that dalbavancin is a safe, welltolerated, and effective antimicrobial agent. In the largest investigation evaluating dalbavancin for the treatment of cSSTIs, it appeared to be as effective as linezolid. Dalbavancin, which is expected to receive FDA approval in 2008, appears to be a promising new antimicrobial agent for the treatment of cSSTIs.

Multicenter Study of the Real-World Use of Ceftaroline versus Vancomycin for Acute Bacterial Skin and Skin Structure Infections

“…The rise of CA-MRSA as a predominant ABSSSI etiology has complicated treatment decisions (5,11). In recent years, industry and the FDA have recognized and responded to the need for safe and effective therapies for serious MRSA infections with the approval of several new antibiotics, including ceftaroline (12,(14)(15)(16). With the availability of various new antibiotics for ABSSSI, antimicrobial stewardship programs (ASPs) have been tasked with formulary decisions.…”

“…Coverage of MRSA is now considered standard for a proportion of ABSSSI patients (11). Fortunately, numerous antibiotics with activity against MRSA have received regulatory approval for ABSSSI in the past 10 years (12)(13)(14)(15)(16)(17). However, clinical outcomes observed in industry registry trials often do not translate to real-world settings.…”

“…Vancomycin has been the standard of care for serious MRSA infections, but recognition of its disadvantages (e.g., poor tissue penetration, therapeutic drug monitoring, and nephrotoxicity) has led many experts to question its future role in ABSSSI treatment (11,(18)(19)(20). Although none of the newer antibiotics have demonstrated superiority over vancomycin in terms of efficacy, these antibiotics may offer other distinct advantages (e.g., tolerability and convenience) for treatment by clinicians (12)(13)(14)(15)(16)(17).…”

Dalbavancin Alone and in Combination with Ceftaroline against Four Different Phenotypes of Staphylococcus aureus in a Simulated Pharmacodynamic/Pharmacokinetic Model

“…Unlike VAN, DAL's disposition is minimally affected by renal function (14,15). Despite high protein binding, DAL has favorable tissue penetration (8,16,17). Furthermore, the long lipophilic lateral chain in DAL's structure (VAN lacks this side chain) extends its half-life, promotes its anchoring to the cell membrane and improves the drug's affinity for the D-alanyl-D-alanine subgroup, which leads to enhancement of its antibacterial activity (18).…”

Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureusIn Vitro

“…Compared to vancomycin, dalbavancin has improved stability in bacterial membranes that is attributed to its extended lipophilic side chain (4,5). With respect to staphylococcal infection, dalbavancin possesses several key advantages, including potent and rapid bactericidal activity, a long half-life, and slow clearance from the body, allowing a once-per-week dosing schedule (6)(7)(8). While dalbavancin offers superior and extended antibacterial activity, its effects on bacterial toxin production have not been directly studied.…”