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

Introduction: (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: 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.