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Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii

Abstract:

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD0, LD50, LD100). Protective dose 50 (PD50) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD0. The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD0 (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD50 was not achieved with non-toxic doses (≤LD0). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p<0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii. © 2011 Springer-Verlag.