Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens

Streit, Jennifer M; Sader, Hélio S.; Fritsche, Thomas R.; Jones, Ronald N.

doi:10.1016/j.diagmicrobio.2005.03.004

Cited by 70 publications

(46 citation statements)

References 13 publications

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“…It has very good in vitro activity against S. aureus (MIC range of Յ0.015 to 0.5 g per ml; MIC 90 of 0.06 g per ml) with no effect of the methicillin resistance phenotype on MICs (334). It retains good activity against staphylococcal strains that are resistant to vancomycin and other new agents such as linezolid and quinupristin-dalfopristin (335). The MIC range is 0.06 to 2 g per ml against hVISA and VISA (335).…”

Section: Potentially Active Antimicrobials In Developmentmentioning

confidence: 98%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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SUMMARY The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

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Section: Potentially Active Antimicrobials In Developmentmentioning

confidence: 98%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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“…It is also the only one to keep useful activity against VRE harboring the vanA genotype or against VRSA [47]. Teicoplanin, dalbavancin, and telavancin remain active on vanB-type resistant strains because they are not inducers for this specific resistance genotype [48,49]. The MICs are 2-4 dilutions higher against VISA than against MRSA for the three drugs [47,50,51].…”

Section: Spectrum Of Activitymentioning

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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“…Vancomycin-susceptible enterococci have demonstrated MICs comparable to S. aureus (0.06-0.5 µg/mL); however, dalbavancin appears to be slightly less active against Enterococcus faecium (MIC of 0.12 µg/mL) than Enterococcus faecalis (MIC of 0.06 µg/mL) (Streit et al 2004). While the MICs for VanB and VanC VRE phenotypes range from 0.12 to 1 µg/mL, the MICs for dalbavancin against VanA enterococci are considerably higher, ranging from 32 to greater than 128 µg/mL (Candiani et al 1999;Jones et al 2001;Jones et al 2003;Streit et al 2005). For enterococci with resistance to linezolid or quinopristin-dalfopristin, dalbavancin appears to display varrying activity depending on the individual strain (Jones et al 2003;Streit et al 2005).…”

Section: Spectrum Of Activitymentioning

confidence: 99%

“…Despite evidence suggesting less potency against VISA, the levels of dalbavancin obtained with a single 1000 mg dose should be adequate to achieve bactericidal activity (Leighton et al 2004). Importantly, dalbavancin retains activity against S. aureus strains with resistance to linezolid or quinupristin/dalfopristin (Jones et al 2003;Flamm et al 2004;Streit et al 2004;Streit et al 2005). Investigators assessing resistance development in staphylococci by both direct selection and serial passage have noted no stable mutants with decreased susceptibility to dalbavancin (Goldstein et al 2007).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…While the MICs for VanB and VanC VRE phenotypes range from 0.12 to 1 µg/mL, the MICs for dalbavancin against VanA enterococci are considerably higher, ranging from 32 to greater than 128 µg/mL (Candiani et al 1999;Jones et al 2001;Jones et al 2003;Streit et al 2005). For enterococci with resistance to linezolid or quinopristin-dalfopristin, dalbavancin appears to display varrying activity depending on the individual strain (Jones et al 2003;Streit et al 2005). Taken together, dalbavancin appears to have excellent activity across the gram-positive spectrum of pathogens causing cSSTIs; however, one should not consider it as a practical therapy for gram-positive pathogens possessing the VanA gene.…”

Section: Spectrum Of Activitymentioning

confidence: 99%

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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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Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens

Cited by 70 publications

References 13 publications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

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

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

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