Isolation, identification, and clinical application of a novel phage targeting carbapenem-resistant Acinetobacter baumannii

Abstract:

[Background] Infections by antibiotic-resistant pathogens pose tremendous threats to human health, and there is an urgent need to develop alternative or adjuvant therapies for classic antibiotics. Phages as the natural predators of bacteria demonstrate promising prospects in treating bacterial infections. [Objective] To isolate virulent phages against carbapenem-resistant Acinetobacter baumannii (CRAB) and then treat CRAB-caused pulmonary infection with the isolated phages.[Methods] We isolated new phages from hospital sewage by using the CRAB clinical strain NAB11B as the host bacteria and then studied the biological and genomic characteristics of the isolated phages. Subsequently, we employed aerosol inhalation of a phage cocktail to treat a patient with CRAB pulmonary infection. Finally, we evaluated the efficacy and safety of phage therapy. [Results] We isolated a novel phage AB_SZL4, which could produce a transparent plaque with a halo in NAB11B lawn and inhibit the growth of NAB11B at low multiplicity of infection (MOI). AB_SZL4 showed the latent period of about 15 min and the burst size of 75 PFU/cell. AB_SZL4 remained stable at pH 3.0–11.0 and 70℃ and below. There was no detrimental gene in the genome of AB_SZL4. NAB11B was eliminated following phage therapy combined with antibiotics within a week, and no phage-related side effect was observed. [Conclusion] AB_SZL4 is a potent lytic phage with great potential for clinical application.

Key words:carbapenem-resistant Acinetobacter baumannii (CRAB);phage;biological characteristics;genomic analysis;phage therapy