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鲍曼不动杆菌:发病机制、毒力因子、新型治疗选择以及对抗微生物药物的耐药机制,重点关注替加环素。

Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline.

机构信息

Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Clin Pharm Ther. 2022 Nov;47(11):1875-1884. doi: 10.1111/jcpt.13787. Epub 2022 Oct 6.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections. A wide range of virulence factors are responsible for pathogenesis and high mortality of A. baumannii including outer membrane proteins, lipopolysaccharide, capsule, phospholipase, nutrient- acquisition systems, efflux pumps, protein secretion systems, quarom sensing and biofilm production. These virulence factors contribute in pathogen survival in stressful conditions and antimicrobial resistance.

COMMENT

According to the World Health Organization (WHO), A. baumannii is one of the most resistant pathogens of ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.). In recent years, resistance to a wide range of antibiotics in A. baumannii has significantly increased and the high emergence of extensively drug resistant (XDR) isolates is challenging. Among therapeutic antibiotics, resistance to tigecycline as a last resort antibiotic has become a global concern. Several mechanisms are involved in tigecycline resistance, the most important of which is RND (Resistance-Nodulation-Division) family efflux pumps overexpression. The development of new therapeutic strategies to confront A. baumannii infections has been very promising in recent years.

WHAT IS NEW AND CONCLUSION

In the present review we highlight microbiological and virulence traits in A. baumannii and peruse the tigecycline resistance mechanisms and novel therapeutic options. Among the novel therapeutic strategies we focus on combination therapy, drug repurposing, novel antibiotics, bacteriophage therapy, antimicrobial peptides (AMPs), human monoclonal antibodies (Hu-mAbs), nanoparticles and gene editing.

摘要

已知和目的

鲍曼不动杆菌是最重要的医院获得性病原体之一,能够引起脑膜炎、肺炎、尿路感染、败血症和伤口感染等感染。多种毒力因子负责鲍曼不动杆菌的发病机制和高死亡率,包括外膜蛋白、脂多糖、荚膜、磷脂酶、营养获取系统、外排泵、蛋白分泌系统、群体感应和生物膜形成。这些毒力因子有助于病原体在应激条件下生存和对抗生素的耐药性。

评论

根据世界卫生组织(WHO)的说法,鲍曼不动杆菌是 ESKAPE 组(粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属)中最具耐药性的病原体之一。近年来,鲍曼不动杆菌对多种抗生素的耐药性显著增加,广泛耐药(XDR)分离株的高出现对治疗构成了挑战。在治疗性抗生素中,最后一道防线抗生素替加环素的耐药性已成为全球关注的问题。替加环素耐药涉及多种机制,其中最重要的是 RND(抗性-结节-分裂)家族外排泵过度表达。近年来,针对鲍曼不动杆菌感染的新治疗策略的发展非常有希望。

新内容和结论

在本综述中,我们强调了鲍曼不动杆菌的微生物学和毒力特征,并探讨了替加环素耐药机制和新的治疗选择。在新的治疗策略中,我们重点关注联合治疗、药物再利用、新型抗生素、噬菌体治疗、抗菌肽(AMPs)、人单克隆抗体(Hu-mAbs)、纳米颗粒和基因编辑。

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