Efficacy of Dalbavancin against Methicillin-Resistant
            <i>Staphylococcus aureus</i>
            in the Rat Granuloma Pouch Infection Model

Jabès, Daniela; Candiani, Gianpaolo; Romanò, Gabriella; Brunati, Cristina; Riva, Simona; Cavaleri, Marco

doi:10.1128/aac.48.4.1118-1123.2004

Cited by 51 publications

(43 citation statements)

References 22 publications

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“…With respect to dalbavancin, it showed activity in a rat granuloma pouch infection model by MSSA and MRSA [113], in neutropenic murine thigh and lung infection models by S. aureus or S. pneumoniae [114], in rabbit endocarditis caused by S. aureus, including strains with reduced susceptibility to glycopeptides [115], in foreign body infection by MRSA in guinea pigs [116], and in an anthrax inhalation model [117].…”

Section: Animal Pharmacodynamic Modelsmentioning

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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Section: Animal Pharmacodynamic Modelsmentioning

confidence: 99%

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

Bambeke

2015

Drugs

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“…Both of these companies have undergone a merger into Vicuron Pharmaceuticals, which filed the new drug application in 2005 and was subsequently acquired by Pfizer (USA). Dalbavancin is more potent than Oritavanacin and has a MIC range of 0.03-1 µg/µL for MRSA, MSSA, VRSA and GISA [79,80]. Pfizer received approval from the U.S. …”

Section: Dalbavancin (Bi397)mentioning

confidence: 99%

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Saxena

Gomber

2010

Open Medicine

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AbstractStaphylococcus aureus is the third most dreaded pathogen posing a severe threat due to its refractory behavior against the current armamentarium of antimicrobial drugs. This is attributed to the evolution of an array of resistance mechanisms responsible for morbidity and mortality globally. Local and international travel has resulted in the movement of drug resistant S. aureus clones from hospitals into communities and further into different geographical areas where they have been responsible for epidemic outbreaks. Thus, there is a dire necessity to refrain further cross movement of these multidrug resistant clones across the globe. The plausible alternative to prevent this situation is by thorough implementation of regulatory aspects of sanitation, formulary usage and development of new therapeutic interventions. Various strategies like exploring novel antibacterial targets, high throughput screening of microbes, combinatorial and synthetic chemistry, combinatorial biosynthesis and vaccine development are being extensively sought to overcome multidrug resistant chronic Staphylococcal infections. The majority of the antibacterial drugs are of microbial origin and are prone to being resisted. Anti-staphylococcal plant natural products that may provide a new alternative to overcome the refractory S.aureus under clinical settings have grossly been unnoticed. The present communication highlights the new chemical entities and therapeutic modalities that are entering the pharmaceutical market or are in the late stages of clinical evaluation to overcome multidrug resistant Staphylococcal infections. The review also explores the possibility of immunity and enzyme-based interventions as new therapeutic modalities and highlights the regulatory concerns on the prescription, usage and formulary development in the developed and developing world to keep the new chemical entities and therapeutic modalities viable to overcome antimicrobial resistance in S. aureus.

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“…These animal studies have demonstrated the effectiveness of dalbavancin in treating infections caused by a variety of gram-positive organisms and have helped defi ne appropriate dosing regimens (Candiani et al 1999;Jabes et al 2004). Candiani et al employed both mouse and rat models in a multifaceted study to evaluate the use dalbavancin in septicemia, lobar pneumonia, and endocarditis (Candiani et al 1999).…”

Section: Animal Studiesmentioning

confidence: 99%

“…In a rodent granuloma pouch model, investigators compared the activities of dalbavancin, linezolid, and vancomycin against experimental MSSA and MRSA bacterial infections (Jabes et al 2004). In this study, suspensions of S. aureus were inoculated into rat granuloma pouches and antibiotic regimens were started shortly after infection.…”

Section: Animal Studiesmentioning

confidence: 99%

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

Ellis¹

2008

TCRM

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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.

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Efficacy of Dalbavancin against Methicillin-Resistant Staphylococcus aureus in the Rat Granuloma Pouch Infection Model

Abstract: Infections due to methicillin-resistant

Cited by 51 publications

References 22 publications

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

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

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

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

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