Once-Weekly Dalbavancin versus Standard-of-Care Antimicrobial Regimens for Treatment of Skin and Soft-Tissue Infections

Seltzer, Elyse; Dorr, Mary Beth; Goldstein, Beth P.; Perry, Marc D.; Dowell, James A.; Henkel, Tim; Skin, Dalbavancin

doi:10.1086/379015

Cited by 218 publications

(154 citation statements)

References 8 publications

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“…Dalbavancin has a prolonged halflife of 6 to 10 days and can potentially be administered as 2 doses 1 week apart. 99 It is currently being studied in phase 3 trials for the treatment of ABSSSIs. 100 Another lipoglycopeptide, oritavancin, is being investigated for ABSSSIs and has the potential to be used as single-dose therapy.…”

Section: Treatment Failurementioning

confidence: 99%

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Amin

Cerceo

Deitelzweig

et al. 2014

Mayo Clinic Proceedings

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The prevalence of skin and soft tissue infections (SSTIs) has been increasing in the United States. These infections are associated with an increase in hospital admissions. Hospitalists play an increasingly important role in the management of these infections and need to use hospital resources efficiently and effectively. When available, observation units are useful for treating low-risk patients who do not require hospital admission. Imaging tools may help to exclude abscesses and necrotizing soft tissue infections; however, surgical exploration remains the principal means of diagnosing necrotizing soft tissue infections. The most common pathogens that cause SSTIs are streptococci and Staphylococcus aureus. Methicillin-resistant S aureus (MRSA) is a prevalent pathogen, and concerns are increasing regarding the unclear distinctions between community-acquired and hospital-acquired MRSA. Other less frequent pathogens that cause SSTIs include Enterococcus species, Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa. Cephalexin and clindamycin are suitable options for infections caused by streptococcal species and methicillin-susceptible S aureus. The increasing resistance of S aureus and Streptococcus pyogenes to erythromycin limits its use in these infections, and better alternatives are available. Parenteral cefazolin, nafcillin, or oxacillin can be used in hospitalized patients with nonpurulent cellulitis caused by streptococci and methicillin-susceptible S aureus. When oral MRSA therapy is indicated, clindamycin, doxycycline, trimethoprim-sulfamethoxazole, or linezolid is appropriate. Vancomycin, linezolid, daptomycin, tigecycline, telavancin, and ceftaroline fosamil are intravenous options that should be used in MRSA infections that require patient hospitalization. In the treatment of patients with SSTIs, hospitalists are at the forefront of providing proper patient care that reduces hospital costs, duration of therapy, and therapeutic failures. This review updates guidelines on the management of SSTIs with a focus on infections caused by S aureus, particularly MRSA, and outlines the role of the hospitalist in the effective management of SSTIs.

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Section: Treatment Failurementioning

confidence: 99%

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Amin

Cerceo

Deitelzweig

et al. 2014

Mayo Clinic Proceedings

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“…In skin and soft tissue infections, a 92-94% microbiological and clinical response respectively was found in an open label phase 2 comparative dosing trial. 73 Clinical success at follow-up visits for the two dose dalbavancin group was 80% for MRSA versus 50% for comparator therapy (which included beta-lactams, clindamycin, vancomycin and linezolid, respectively).…”

Section: Dalbavancinmentioning

confidence: 92%

“…This antibiotic has been evaluated for catheterrelated bacteremia 72 and skin and soft tissue infections. 73 Dalbavancin was effective and well tolerated in adult patients with catheter-related bacteremia caused by coagulasenegative Staphylococci, MSSA and MRSA in a comparative trial with vancomycin. In skin and soft tissue infections, a 92-94% microbiological and clinical response respectively was found in an open label phase 2 comparative dosing trial.…”

Section: Dalbavancinmentioning

confidence: 97%

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

Manfredi¹,

Sabbatani²

2010

Braz J Infect Dis

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Introduction: methicillin-and also vancomycin (glycopeptide)-resistant Gram-positive organisms have emerged as an increasingly problematic cause of hospital-acquired infections, also spreading into the community. Vancomycin (glycopeptide) resistance has emerged primarily among Enterococci, but the MIC values of vancomycin for the entire Staphylococcus species are also increasing worldwide. Material and Methods: the aim of our review is to evaluate the efficacy and tolerability of newer antibiotics with activity against methicillin-resistant and glycopeptide-resistant Gram-positive cocci, on the ground of our experience at a tertiary care metropolitan Hospital, and the most recent literature evidences in this field. Results: Quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline show an excellent in vitro activity, comparable to the activity of vancomycin and teicoplanin for methicillin-resistant staphylococci, and superior to the one that vancomycin for vancomycin-resistant isolates. Dalbavancin, televancin, and oritavancin are new lipoglycopeptide agents with excellent activity against Gram-positive cocci, and have superior pharmacodynamics properties compared to vancomycin. We review the bacterial spectrum, clinical indications and practical use, pharmacologic properties, and expected adverse events and contraindications associated with each of these novel antimicrobial agents, compared with the present standard of care. Discussion: linezolid activity is substantially comparable to that of vancomycin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although its penetration into the respiratory tract is exceptionally elevated. Tigecycline has activity against both Enterococus species and MRSA; it is also active against a broad spectrum of Enterobacteriaceae and anaerobes, which allows for use intraabdominal, diabetic foot and surgical infections. Daptomycin has a rapid bactericidal activity for Staphylococcus aureus and it is approved in severe complications, such as bacteremia and right-sided endocarditis. It cannot be used to treat pneumonia and respiratory diseases, due to its inactivation in the presence of pulmonary surfactant.

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“…The adoption of an updated test-of-cure clinical response (C90 % reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibacterialcs/significant surgical procedures) concluded that there was equivalence between telavancin-and vancomycin-treated patients (68.0 vs. 63.3 % cure rates). Phase II studies determined the optimal dosing regimen as being a single dose of 1200 mg for oritavancin (SIM-PLIFI trial [3]), a 1000 mg dose at day 1 followed by a 500 mg dose at day 7 for dalbavancin [136], and a 10 mg/ kg daily dose for telavancin (FAST 2 trial [137]). Thus, a possible advantage of oritavancin and dalbavancin resides in their simplified therapeutic scheme, which may even allow their use for home therapy [138,139].…”

Section: Registered Indicationsmentioning

confidence: 99%

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

Bambeke

2015

Drugs

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Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Grampositive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospitalacquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections. Key PointsNew lipoglycopeptides (telavancin, oritavancin, dalbavancin) differ from vancomycin by the presence of a lipophilic side chain, which profoundly modifies their pharmacokinetic and/or pharmacodynamic profile.Among these agents, telavancin and oritavancin have multiple modes of action and are highly bactericidal.Oritavancin and dalbavancin have prolonged halflives, allowing for their use a single-dose or twodose (once-a-week) regimen, respectively. These three drugs are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin is indicated for hospital-acquired and ventilator-associated bacterial pneumonia.

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Once-Weekly Dalbavancin versus Standard-of-Care Antimicrobial Regimens for Treatment of Skin and Soft-Tissue Infections

Cited by 218 publications

References 8 publications

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

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