Carbapenem-resistant Acinetobacter baumannii bloodstream infections and specific phages isolation, analysis and application.

Abstract

INTRODUCTION: Antimicrobial resistance poses a major challenge in the treatment ofworldwide, especially(CRAB) bloodstream infections. OBJECTIVES: The objective of this study was to isolate and characterize a CRAB-targeting bacteriophage and to evaluate its therapeutic potential, alone and in combination with polymyxin B. METHODS: From January 2020 to September 2025, adult patients withbloodstream infection were enrolled. Clinically relevant data were collected.strains were isolated from clinical samples and the phage was isolated from wastewater samples collected from hospital by double-layer agar plate method. The synergistic activity of phage-polymyxin B combination therapy was assessed by checkerboard analysis and time-kill assays. BALB/c mice were infected with a CRAB suspension via tail vein to establish the model and were subsequently treated with the phage and phage-antibiotic combination. RESULTS: A total of 50 patients suffered from bloodstream infections caused by Acinetobacter baumannii. Among them, 34 (68%) cases were classified as CRAB. Compared with CSAB, they underwent a longer duration of mechanical ventilation(13.00(6.00,28.00) vs.3.00(2.00,4.00),P =0.019), used more triple therapy(9.41% vs.0%,P=0.041), and had a higher in-hospital mortality(82.35% vs.18.75%,P <0.001). Synergistic antibacterial activity between the phage and colistin B was demonstrated using the checkerboard assay and time-kill curve analysis. In a murine bacteremia model, the vB_AbaP_CV1-antibiotic combination significantly reduced tissue bacterial loads, attenuated inflammatory responses, and ameliorated clinical manifestations. Notably, the combined therapy exhibited superior therapeutic efficacy compared to either monotherapy alone. CONCLUSION: CRAB bloodstream infections are associated with high mortality and poor outcomes. vB_AbaP_CV1 can lyse the CRAB strains. Both phage monotherapy and the phage-colistin B combination exhibited therapeutic efficacy, with the combined regimen yielding the optimal outcome.