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抗生素耐药机制

Antibiotic Resistance Mechanisms.

作者信息

Kyriakidis Ioannis, Vasileiou Eleni, Pana Zoi Dorothea, Tragiannidis Athanasios

机构信息

Pediatric and Adolescent Hematology-Oncology Unit, 2nd Department of Pediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece.

Laboratory of Cytogenetics and Molecular Genetics, Department of Biology, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece.

出版信息

Pathogens. 2021 Mar 19;10(3):373. doi: 10.3390/pathogens10030373.

Abstract

is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.

摘要

是一种革兰氏阴性ESKAPE微生物,通过引起与高死亡率相关的严重侵袭性(主要是医院内)感染对公众健康构成威胁。在过去几年中,这种病原体表现出多重耐药性(MDR),主要是由于广泛的抗生素滥用和管理不善。多重耐药分离株与长期住院病史、导管的存在和机械通气有关,而免疫功能低下和重症宿主易发生侵袭性感染。下一代测序技术彻底改变了严重感染的诊断,根据各自耐药基因的鉴定有助于及时诊断和制定个性化治疗方案。本综述的目的是详细描述目前关于人类中β-内酰胺类(青霉素、头孢菌素、碳青霉烯类、单环β-内酰胺类和β-内酰胺酶抑制剂)、氨基糖苷类、四环素类、氟喹诺酮类、大环内酯类、林可酰胺类、链阳菌素类抗生素、多粘菌素类及其他(氯霉素、恶唑烷酮类、利福霉素类、磷霉素、二氨基嘧啶类、磺胺类、糖肽类和脂肽类抗生素)耐药机制的遗传背景的所有知识。抗菌药物耐药机制主要涉及通过细菌膜的抗生素转运调节、抗生素靶位点的改变以及导致抗生素失活的酶促修饰。还讨论了可能影响抗生素敏感性谱并赋予耐药性的毒力因子。对COVID-19大流行期间SARS-CoV-2合并感染病例在耐药谱和多重耐药基因方面的报告进行了调查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4665/8003822/7f3330b065f2/pathogens-10-00373-g001.jpg

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