Bacteriophage treatment is effective against carbapenem-resistant Klebsiella pneumoniae (KPC) in a neutropenic murine model of gastrointestinal translocation and renal infection

• DOI: 10.1128/aac.00919-24
• Publication Date: 2024-12-20T14:00:16Z
• Authors: Panagiotis Zagali...; Jordyn Michalik-P...; Eleftheria Mavridou; Ethan Naing; Ioannis S. Viziri...; Dimitrios Chatzid...; Jason J. Gill; Thomas J. Walsh
• Keywords: Phage therapy; Viremia

ABSTRACT Carbapenemase-producing Klebsiella pneumoniae (KPC) are globally emerging pathogens that cause life-threatening infections. Novel treatment alternatives urgently needed. We therefore investigated the effectiveness of three novel bacteriophages (Spivey, Pharr, and Soft) in a neutropenic murine model KPC gastrointestinal colonization, translocation, disseminated infection. Bacteriophage efficacy was determined by residual bacterial burden (CFU/g) kidneys. Parallel studies were conducted bacteriophage pharmacokinetics resistance. Treatment mice with 5 × 10 9 PFU phage cocktail via intraperitoneal injection effective significantly reducing renal CFU 100-fold ( P < 0.01) when administered every 24 h 1000-fold 12 h. Moreover, combination ceftazidime-avibactam produced synergistic effect, resulting -fold reduction cecum kidney 0.001 both tissues). Prophylactic administration oral gavage did not prevent translocation to decay linear regression ln mean concentrations demonstrated R 2 values plasma 0.941, 0.976, 0.918, half-lives t 1/2 = 2.5 Furthermore, phage-resistant mutant displayed increased sensitivity serum killing vitro , but show significant defects infection vivo . A alone synergy ceftazidime/avibactam experimental mice.