In vivo pharmacodynamic study of the novel polymyxin MRX-8.

Abstract

In previous studies, polymyxin MRX-8 demonstrated potent in vitro antibacterial activity with a reduced nephrotoxicity risk and an improved PK/PD profile compared with polymyxin B. In this study, the in vivo antibacterial efficacy of intravenously administered MRX-8 was evaluated in murine models of systemic infection (induced by intraperitoneal injection), lung infection (induced by intratracheal route inoculation), and ascending urinary tract infection (induced by intraurethral inoculation) with P. aeruginosa, K. pneumoniae, E. coli, and A. baumannii as the challenging pathogens. MRX-8 demonstrated superiority to polymyxin B against carbapenem-resistant K. pneumoniae, P. aeruginosa and E. coli infections; however, the efficacy of MRX-8 was less than or comparable with that of polymyxin B against carbapenem-resistant A. baumannii infections. The results suggest MRX-8 could be an efficacious treatment alternative versus Gram-negative, treatment-resistant pathogens that can confound current antimicrobial agents.