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

Abstract

Acute bacterial skin and skin structure infections (ABSSSI) are a common disease causing patients to seek treatment through the health care system. With the continued increase of drug-resistant bacterial pathogens, these infections are becoming more difficult to successfully cure. Lipoglycopeptides have unique properties that allow the drug to remain active toward both common and challenging pathogens at the infected site for lengthy periods of time. Dalbavancin, a new lipoglycopeptide, provides two unique dosing regimens for the treatment of ABSSSI. The original regimen of 1,000 mg intravenous infusion followed by a 500 mg intravenous infusion after a week has been shown as safe and effective in multiple, randomized noninferiority trials. These studies also demonstrated that dalbavancin was similar to standard regimens in terms of both safety and tolerability. Recently a single 1,500 mg dose was demonstrated to be equivalent to the dalbavancin two-dose regimen for treating ABSSSI. With the introduction of dalbavancin, clinicians have the option to provide an intravenous antimicrobial agent shown to be as effective as traditional therapies, without requiring admission into the hospitals or prescribing a medication which may not be utilized optimally. Further understanding of dalbavancin and its unusual properties can provide unique treatment situations with potential benefits for both the patient and the overall health care system, which should be further explored.

Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

“…5 The pharmacokinetics (PK) of dalbavancin in humans is linear, dose-proportional, and characterized by high protein binding 7,8 ; approximately 93% of an intravenous dose was reported to be bound to serum albumin, with the remaining 7% existing in unbound form, a proportion that is largely unchanged by drug concentration, renal impairment, or hepatic function. 6,9,10 Initial distribution occurs in a volume of approximately 10 L, and drug levels in plasma decline rapidly over the first 48 hours as the drug distributes extensively into body tissues, including bone and articular tissue, with a total volume of distribution (V d ) of nearly 16 L. 11,12 In healthy volunteers, approximately onethird of a 1000-mg intravenous dose of dalbavancin is excreted in urine unmodified, 8 with an additional one-third of dalbavancin excreted in the feces and a further 12% excreted as a minor metabolite, hydroxyldalbavancin, by 42 days postdose. 10,13 As a result, nonrenal methods play a major role in dalbavancin metabolism.…”

“…6,9,10 Initial distribution occurs in a volume of approximately 10 L, and drug levels in plasma decline rapidly over the first 48 hours as the drug distributes extensively into body tissues, including bone and articular tissue, with a total volume of distribution (V d ) of nearly 16 L. 11,12 In healthy volunteers, approximately onethird of a 1000-mg intravenous dose of dalbavancin is excreted in urine unmodified, 8 with an additional one-third of dalbavancin excreted in the feces and a further 12% excreted as a minor metabolite, hydroxyldalbavancin, by 42 days postdose. 10,13 As a result, nonrenal methods play a major role in dalbavancin metabolism. 13 Total drug clearance has been estimated to be approximately 0.04 L/h in healthy subjects 7 and 0.058 L/h in patients.…”

Resistência aos antimicrobianos: uma revisão dos desafios na busca por novas alternativas de tratamento

“…21 Em alternativa, o efeito benéfico proveniente da associação de duas drogas ou mais, vem apresentando-se mais intenso do que quando administradas de forma isolada. 20 Oliveira, 2014 20 Lopes, 2009 21 Lin et al, 2015 17 Lin et al 24 Fala, 2015 25 Brade, Rybak, Rybak, 2016 26 Giancola et al,…”

“…3 Em vista disso, as indústrias farmacêuticas enfrentam desafios para o desenvolvimento constante de novos medicamentos, tratamentos e estratégias a fim de sanar essa calamidade global, como ocorre na aplicação nismos de extrema relevância global (Quadro 1). 11 tâncias antimicrobianas, bem como documentos relacionados ao registro de novas drogas por agências de saúde internacionais. Os critérios de exclusão incluíram teses, anais de congressos ou conferências, relatórios técnicos ou artigos que não tratavam exclusivamente do tema exposto.…”

Tedizolid in skin and skin structure infections: brave new world?

“…Moreover, the common adverse event of bone marrow suppression often observed after long-term treatment with linezolid is an obstacle for the specific antibiotic. Fortunately, new agents are in the pipeline, enabling single-dose administration, such as dalbavancin (1000 mg intravenous infusion followed by a 500 mg intravenous infusion after a week) or oritavancin (as a single dose treatment) and may improve the outlook of patients with ABSSSI [6,7].…”