Efficacy of Novel Antistaphylococcal Ectolysin P128 in a Rat Model of Methicillin-Resistant Staphylococcus aureus Bacteremia

Staphylococcus aureus causes systemic infections with high morbidity and mortality, and the emergence of drug-resistant strains is a rapidly growing clinical concern. Novel therapeutic agents are required to tackleS. aureus infections. P128 is a bacteriophage-derived chimeric ectolysin with potent and rapid bactericidal activity againstS. aureus . In the present study, the efficacy of P128 was evaluated in a newly developed rat model ofS. aureus bacteremia. Prior toin vivo testing, P128 was shown to be stable in whole blood by incubation in rat blood for up to 6 h and testing its bactericidal activity against the methicillin-resistantS. aureus isolate USA300. Rats succumbed to intravenous challenge with 109 CFU ofS. aureus USA300, resulting in 80 to 100% mortality by day 14. Evaluation of the bacterial load in various organs at 96 h postinfection revealed high bacterial counts in the kidney, and this correlated with the presence of renal abscesses. Treatment of infected animals with P128 either by intravenous bolus administration via tail vein or by 1-h infusion via the jugular vein at 2 h postinfection resulted in the dose-dependent survival of rats. P128 treatment also resulted in very few or no abscesses in the kidneys. These data show that P128 is stable in the physiological milieu and that intravenous treatment with P128 is highly effective in rescuing rats fromS. aureus bacteremia. P128 can be a novel therapeutic option for treatment ofS. aureus systemic infections.