In-vitro and in-vivo antibacterial activity of BI 397, a new semi-synthetic glycopeptide antibiotic

Abstract

BI 397 (formerly A-A-1) is a semisynthetic derivative of the teicoplanin-like glycopeptide A40926. It was more active in vitro against staphylococci (including some teicoplanin-resistant strains) than teicoplanin and vancomycin. Against streptococci (including penicillin-resistant strains) BI 397 has activity comparable with that of teicoplanin and better than vancomycin. BI 397, when administered to rats by the i.v. route, gives high and long lasting blood levels. It shows excellent activity in models of acute septicaemia in immunocompetent and neutropenic mice. In a rat staphylococcal endocarditis model it is as effective as teicoplanin and vancomycin at reducing bacterial loads in the heart, but at lower dosages and with a reduced number of daily treatments compared with the two glycopeptide controls. BI 397 is highly efficacious in clearing penicillin-susceptible and -resistant pneumococci from lungs of immunocompetent and neutropenic rats. The data from these studies show that BI 397 combines an excellent in-vitro antibacterial activity with favourable pharmacokinetic behaviour resulting in potent in-vivo activity.

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

“…Dalbavancin appeared to be slightly more active than vancomycin in the immunocompetent mice. In the immunocompromised mice infected with S. epidermidis, dalbavancin was by far the most active agent with a signifi cantly lower ED 50 ; however, dalbavancin was slightly less active than teicoplanin against E. faecalis in the immunocompromised mice (Candiani et al 1999).…”

“…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).…”

“…In the lobar pneumonia arm of this investigation, immunocompetent and neutropenic rats were infected with penicillin-susceptible and penicillin-resistant strains of S. pneumoniae (Candiani et al 1999). This pneumonia model demonstrated that animals that received dalbavancin had decreased bacterial load and better survival than those receiving 3 days of penicillin-G regardless of penicillin susceptibility.…”

“…MICs for MSSA, MRSA, and Coagulase negative Staphylococcus (CoNS) range from 0.06 to 0.5 µg/mL in most reports (Candiani et al 1999;Woodford 2003;Flamm et al 2004;Streit et al 2004;Jones et al 2005;Lin et al 2005;Goldstein et al 2006b). Dalbavancin displays generally lower MICs against staphylococci when compared to other agents (Candiani et al 1999;Malabarba and Ciabatti 2001;Woodford 2003;Streit et al 2004;Lin et al 2005). Dalbavancin has been tested against several isolates with reduced susceptibility to vancomycin and has generally been shown to display decreased activity against these strains.…”

“…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).…”