In vivo pharmacokinetics, therapeutic efficacy and immune response of bacteriophage vB_AbaSt_W16 against carbapenem-resistant Acinetobacter baumannii

초록

Background The increasing prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) infections necessitates alternative therapeutic strategies. Bacteriophage therapy has emerged as a promising approach, yet its clinical implementation is hindered by limited pharmacokinetic (PK) and pharmacodynamic (PD) data.Methods The PK and PD properties of Acinetobacter phage vB_AbaSt_W16 were evaluated in a murine model. Systemic distribution, clearance kinetics and efficacy were assessed following oral (PO) and intraperitoneal (IP) administration. Conventional PK/PD analysis and real-time fluorescence imaging were used to examine in vivo phage dynamics.Results After administration, vB_AbaSt_W16 rapidly disseminated systemically within 1 h, reaching peak concentrations at 8 h. Most tissues cleared the phage within 72 h, though residual amounts persisted in the spleen for up to 92 h. In a murine infection model, vB_AbaSt_W16 demonstrated potent antibacterial activity, reducing CRAB bacterial loads by 4-7 log(1)(0) cfu/mL within 24 h. Compared with PO administration, IP administration resulted in higher systemic bioavailability and bacterial clearance. Fluorescence imaging enabled non-invasive, real-time monitoring of phage distribution, demonstrating its utility as a PK assessment tool. Notably, phage treatment did not trigger significant pro-inflammatory cytokine release (TNF-alpha, IL-6) in healthy mice and effectively reduced CRAB-induced inflammation.Conclusions These findings highlight the therapeutic potential of vB_AbaSt_W16 and provide critical insights into its PK behaviour. The results support further clinical development of this phage for CRAB infections.

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