PredictingIn VivoEfficacy of Therapeutic Bacteriophages Used To Treat Pulmonary Infections

Abstract

ABSTRACTThe potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis ofin vitroobservations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain ofPseudomonas aeruginosato compare the activitiesin vitroandin vivoof a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found betweenin vitroandin vivoactivity. While the remaining two bacteriophages were activein vitro, they were not sufficiently activein vivounder similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficientin vivo, supporting a personalized approach favoring an optimal treatment.