Activities of Dalbavancin In Vitro and in a Rabbit Model of Experimental Endocarditis Due to Staphylococcus aureus with or without Reduced Susceptibility to Vancomycin and Teicoplanin

Abstract

For the treatment of rabbit endocarditis, dalbavancin given once daily (10 mg/kg of body weight for 4 days) or as a single 40-mg/kg dose was active against Staphylococcus aureus with or without reduced susceptibility to glycopeptides, as expected from its good in vitro activity, even in broth supplemented with 90% serum and given its prolonged elimination half-life.Worldwide emergence of strains of Staphylococcus aureus with reduced susceptibility to glycopeptides (glycopeptide-intermediate S. aureus [GISA]) (2, 3, 8) emphasizes the need for new therapeutic options. Previous studies showed that dalbavancin (BI-397), a new semisynthetic glycopeptide antibiotic, is active in vitro and in animal models (1, 4) against gram-positive microorganisms, including methicillin-resistant S. aureus. In addition, dalbavancin has unique pharmacokinetics, with high levels in plasma which are sustained in humans for a long time due to its very long elimination half-life of approximately 1 week

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

“…Notably, the dalbavancin MICs are higher for hVISA and VISA strains, and higher concentrations were required to achieve bactericidal activity than for MRSA in an in vitro model (28); however, the clinical implications of this finding are unclear. In an endocarditis model, dalbavancin was equally effective against VISA and teicoplanin-intermediate S. aureus, and the bactericidal results were nearly identical (173).…”

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

“…Additionally, the once-daily dalbavancin dose was more effective than the single dose regimen. This endocarditis model provided evidence that dalbavancin has comparable activity to vancomycin against S. aureus with reduced glycopeptide susceptibility (LeFort et al 2004).…”

“…Dalbavancin has been tested against several isolates with reduced susceptibility to vancomycin and has generally been shown to display decreased activity against these strains. Three VISA isolates tested against dalbavancin were noted to have MICs ranging from 1.0 to 4.0 µg/mL, and one VRSA isolate displayed a MIC of Ͻ0.5 µg/mL (Bozdogan et al 2003;Lefort et al 2004;Goldstein et al 2007). 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).…”

“…LeFort et al also evaluated dalbavancin with a rabbit endocarditis model using S. aureus strains susceptible to vancomycin and teicoplanin (MICs of 2 and 4 µg/mL, respectively) and strains with reduced susceptibility to both glycopeptides (MICs of 8 and 16 µg/mL, respectively) (LeFort et al 2004). In this model, rabbits were infected with S. aureus and then treated with dalbavancin 10 mg/kg once daily for 4 days or with a single 40 mg/kg dose of the agent.…”

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

“…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].…”