Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently.

Autor: Wang WX; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Wu JZ; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China; Department of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China., Zhang BL; Department of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China., Yu JY; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China; Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China., Han LM; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Lu XL; Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China., Li H; Department of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China., Fu SY; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Ren YY; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Dong H; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Xu Y; Department of Geriatric Medicine, Jiangxi Provincial People's Hospital, Nanchang, China., Wang GT; Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China., Gao JH; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Wang C; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Chen XZ; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China., Liu DX; Department of pathology, the Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, China., Huang Y; Department of Infection Control and Management, the Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, China., Yu JH; Department of Clinical Laboratory, the Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, China., Wang SW; Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China., Yang YF; The Clinical Infectious Disease Center of Nanjing, Nanjing, China. Electronic address: yangyongfeng@njucm.edu.cn., Chen W; Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: njyy039@njucm.edu.cn.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 Aug; Vol. 64 (2), pp. 107220. Date of Electronic Publication: 2024 May 28.
DOI: 10.1016/j.ijantimicag.2024.107220
Abstrakt: Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.
(Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
Databáze: MEDLINE
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