鲍曼不动杆菌对碳青霉烯类耐药机制研究进展

出现碳青霉烯酶是难治性感染的主要原因,同时也是鲍曼不动杆菌产生耐药的最重要机制.本文结合国内外诸多文献资料,深入探讨了鲍曼不动杆菌对碳青霉烯类耐药机制的研究进展.鲍曼不动杆菌对碳青霉烯类抗生素耐药的机制主要包括:质子泵的外排作用、外膜通透性的改变、PBPs的改变、碳青霉烯酶的产生.     

耐碳青霉烯类鲍曼不动杆菌的耐药机制及其同源性分析

目的:分析耐碳青霉烯类鲍曼不动杆菌的耐药机制及其同源性。方法:收集2016年1月—2017年6月间临床分离的耐碳青霉烯类鲍曼不动杆菌感染资料,分析资料中经Vitek-2 Compact型全自动细菌分析系统鉴定和药敏试验并按照CLSI标准判读的结果,其中鲍曼不动杆菌编码的OXA-23型碳青霉烯酶blaOXA-23基因,采用PCR法检测;对分离出的鲍曼不动杆菌采用ERIC-PCR进行同源性分析,以此了解其流行病学特征。结果:共分离出碳青霉烯类抗菌药物耐药鲍曼不动杆菌17株,临床所用抗菌药物对耐药鲍曼不动杆菌具有较差的敏感性;16株碳青霉烯类抗菌药物耐药鲍曼不动杆菌均存在同源性。结论:产OXA-23型碳青霉烯酶在介导鲍曼不动杆菌碳青霉烯类抗生素耐药过程中起着传播机制,医院应加强此菌院内感染防控措施,严防院内感染的发生。     

医院五年鲍曼不动杆菌耐药性分析

鲍曼不动杆菌常引起呼吸机相关性肺炎、泌尿系统感染和败血症等[1],是医院感染呼吸机相关性肺炎的常见病原菌[2].自2010年,我院开始分离出多重耐药鲍曼不动杆菌(MDR-Ab)、泛耐药鲍曼不动杆菌(PDR-Ab)以及耐碳青霉烯类鲍曼不动杆菌(CR-Ab)等鲍曼不动杆菌耐药菌株,为了解我院鲍曼不动杆菌感染及其耐药特点,本研究对所有送检标本分离的鲍曼不动杆菌的试验结果进行分析,现报道如下.     

耐碳青霉烯鲍曼不动杆菌耐药机制研究进展

鲍曼不动杆菌(Acinetobacter baumannii,Ab)作为医院感染中最重要的致病菌之一,因抗生素不合理使用等多个因素使耐碳青霉烯鲍曼不动杆菌(Carbapenem resistant Acinetobacter baumannii,CRAB)检出率逐年上升,导致交叉耐药或多重耐药。其耐药机制主要包括碳青霉烯酶产生、外膜孔蛋白改变、外排泵活性增强、青霉素结合蛋白位点改变及整合子机制。本文就耐碳青霉烯鲍曼不动杆菌耐药机制研究进展做一综述,为临床抗感染治疗及新药研制提供参考。     

产碳青霉烯酶鲍曼不动杆菌检测及耐药性分析

目的 了解鲍曼不动杆菌产碳青霉烯酶状况及耐药性,为临床合理应用抗菌药物提供依据.方法 2011年7-12月南京医科大学第一附属医院住院患者标本中分离出鲍曼不动杆菌361株,对其来源、科室分布及耐药率进行统计分析,药物敏感试验采用K-B法,用改良Hodge试验检测鲍曼不动杆菌产碳青霉烯酶的情况.结果 分离出的361株鲍曼不动杆菌中耐亚胺培南和美罗培南菌株328株,改良Hodge试验阳性株278株(84.8％).临床常用的16种抗菌药物中对多粘菌素E耐药率8.4％,米诺环素耐药率47.5％,对其他14种抗生素耐药率均＞60％.结论 鲍曼不动杆菌耐药性升高主要是产碳青霉烯酶;多粘菌素对产碳青霉烯酶的鲍曼不动杆菌有较好的抑菌作用.     

耐碳青霉烯鲍曼不动杆菌流行特征及耐药基因分析

目的调查分析我院2009年医院内获得性鲍曼不动杆菌对各种抗菌药物的耐药性,研究耐碳青霉烯鲍曼不动杆菌感染的克隆流行情况以及碳青霉烯酶基因型。方法用琼脂稀释法进行药敏试验,按CLSI（2009）标准判断细菌耐药性,并用PFGE法对2009年的102株对碳青霉烯耐药菌进行同源性分析,多重PCR扩增碳青霉烯酶基因bla_OXA-51like,bla_OXA-24like,bla_OXA-58like。结果药敏试验结果显示鲍曼不动杆菌对米诺环素、替加环素、多粘菌素B耐药率较低,对碳青霉烯耐药高。PFGE结果显示我院存在A/B/C克隆株流行,主要分布于呼吸科以及ICU等病房,时间上呈散发流行。102株耐碳青霉烯鲍曼不动杆菌产OXA-23型碳青霉烯酶率为71.6%,产OXA-51型碳青霉烯酶率为84.3%,另外仅2株检出OXA-24型碳青霉烯酶,3株检出（）XA-58型碳青霉烯酶。结论我院在呼吸科以及ICU等病房存在A/B/C克隆株流行,碳青霉烯酶基因型以OXA-23、OXA-51型为主,由于对多种抗菌药物尤其是碳青霉烯类抗生素耐药性的增强和克隆株的流行,应积极采取有效措施预防和控制鲍曼不动杆菌感染。     

合肥市三家医院鲍曼不动杆菌的耐药特征和碳青霉烯酶基因检测

目的 了解合肥市3家三级医院鲍曼不动杆菌的耐药性特点,分析对碳青霉烯类敏感和耐药的鲍曼不动杆菌携带碳青霉烯酶基因情况。方法 利用Whonet 5.6数据库对2018年1月—2020年12月合肥市3家三级医院分离的鲍曼不动杆菌菌株进行回顾性分析,统计3年间鲍曼不动杆菌菌株数量和药敏情况;随机挑取各家医院冻存的对碳青霉烯类耐药鲍曼不动杆菌44株(耐药组)及敏感菌15株(对照组),利用PCR技术检测12种碳青霉烯酶基因(bla_OXA-23、bla_OXA-24、bla_OXA-51、bla_OXA-58、bla_OXA-143、bla_OXA-235、bla_IMP、bla_VIM、bla_SIM、bla_NDM、bla_TEM、bla_KPC)的携带情况。结果 临床分离的鲍曼不动杆菌菌株约有70%对碳青霉烯类药物耐药。2020年分离的鲍曼不动杆菌对头孢...     

重症监护病房耐碳青霉烯鲍曼不动杆菌6种耐药基因检测

目的 研究医院重症监护病房(intensive care unit,ICU)患者感染鲍曼不动杆菌的耐药性及耐药基因,以指导临床合理用药,控制ICU病房感染暴发流行。方法 采用VITEK2-Compact全自动细菌鉴定药敏系统对细菌进行鉴定及药敏试验,用聚合酶链反应(polymerase chain reaction,PCR)方法检测6种常见碳青霉烯酶耐药基因(blaIMP、blaVIM、blaNDM、blaOXA-23、blaOXA-24和blaOXA-58)。结果 38株耐碳青霉烯鲍曼不动杆菌对15种临床常用青霉素类、头孢菌素类、氨基糖苷类、喹诺酮类及β-内酰胺酶抑制剂类抗菌药物全部耐药,对头孢哌酮/舒巴坦、米诺环素的耐药率分别为92.1%和81.6%,仅对替加环素保持较高敏感性,敏感率为94.7%。38株CRAB中携带blaOXA-23基因共36株(94.7%),未检出blaIMP、blaVIM、blaNDM、blaOXA-24和blaOXA-58基因。结论 我院ICU分离耐碳青霉烯鲍曼不动杆菌对临床常用抗菌药物耐药广泛,携带blaOXA-23基因是可能该院ICU耐碳青霉烯鲍曼不动杆菌对碳青霉烯类抗菌药物耐药的主要原因。临床医生应合理使用抗菌药物,加强细菌耐药性监测,防止耐药菌株的产生和进一步传播。     

鲍曼不动杆菌的耐药性及产ESBL和碳青霉烯酶分析

目的:分析我院鲍曼不动杆菌的耐药性及产超广谱β-内酰胺酶(ESBL)和产碳青霉烯酶情况.方法:K-B法进行药物敏感试验,运用表型确证试验检测ESBL,改良Hodge试验检测碳青霉烯酶.结果:135株鲍曼不动杆菌中,对亚胺培南和关罗培南的耐药率高达72.6％,对阿米卡星、头孢噻肟等10种抗菌药物耐药率为61.5％～100.0％,对头孢哌酮/舒巴坦的耐药率最低为34.8％,其次是左氧氟沙星耐药率为54.1％.其中有22株检出ESBL占16.3％;46株检出碳青霉烯酶占34.1％.结论:我院鲍曼不动杆菌耐药率高,应加强细菌检测和药敏试验,指导临床合理应用抗茵药物.对于临床经验用药建议选用头孢哌酮/舒巴坦;鲍曼不动杆菌对β-内酰胺类药物耐药可能与产ESBL和碳青霉烯酶有关.     

耐碳青霉烯鲍曼不动杆菌OXA酶基因研究

目的 检测鲍曼不动杆菌对β-内酰胺类抗生素的耐药性,了解耐碳青霉烯鲍曼不动杆菌OXA酶基因、插入序列和Ⅰ类整合酶基因的分布.方法 采用琼脂二倍稀释法检测90株鲍曼不动杆菌对20种β-内酰胺类抗菌药物的最低抑菌浓度,常规PCR检测耐碳青霉烯鲍曼不动杆菌的4种OXA酶基因、插入序列和Ⅰ类整合酶基因.结果 90株鲍曼不动杆菌对20种β-内酰胺类抗菌药物的耐药性为5.7%～94.2%; 21株耐碳青霉烯鲍曼不动杆菌中,8株OXA-23阳性,且ISAbal同为阳性,4株OXA-51阳性,1株Ⅰ类整合酶基因阳性.结论 临床分离的鲍曼不动杆菌对β-内酰胺类抗生素耐药形势严峻,耐碳青霉烯鲍曼不动杆菌OXA酶基因和ISAbal检出率均很高.     

Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp

Carbapenem resistance in Acinetobacter baumannii is a growing public health concern and is most often mediated by OXA carbapenemases. We describe a novel multiplex polymerase chain reaction (PCR) assay able to detect and distinguish alleles encoding three subgroups of acquired OXA carbapenemases (OXA-23-like, OXA-24-like and OXA-58-like) that are scattered in Acinetobacter spp., and a fourth subgroup, OXA-51-like, which appears to be intrinsic to Acinetobacter baumannii. Isolates belonging to two prevalent UK A. baumannii 'OXA' clones (OXA-23 clones 1 and 2) had alleles encoding both an intrinsic OXA-51-like and an acquired OXA-23 enzyme, whereas isolates of the 'SE clone' had only an intrinsic bla(OXA-51-like) allele. Genes encoding OXA-58 were detected (with bla(OXA-51-like)) in a cluster of related isolates from a single hospital. This simple assay will assist in monitoring the mechanisms responsible for carbapenem resistance in Acinetobacter spp.     

The impact of carbapenemases on antimicrobial development and therapy

Carbapenems have been the most successful beta-lactam antibiotics in evading bacterial resistance. Nevertheless, acquired carbapenemases are increasingly reported, mostly in Pseudomonas and Acinetobacter isolates but occasionally also in Enterobacteriaceae. They include beta-lactamases of classes B (IMP and VIM), D (OXA-23 to -27) and A (IMI, KPC, NMC and SME). Major outbreaks of producers have occurred in a few centers and, in the US, there has been progressive erosion of carbapenem activity against Acinetobacter species, maybe due to carbapenemases. Acquired carbapenemases are still sufficiently rare not to have placed widespread constraints on chemotherapy, but there is reasonable concern that they will become a greater problem in the future. This is a good argument for continued caution with carbapenem use, and for extending this prudence to the oral and long half-life carbapenems shortly to become available. Most carbapenemase producers are broadly resistant to beta-lactams, and many are also resistant to fluoroquinolones and aminoglycosides. Clinicians facing infections caused by carbapenemase producers consequently are forced to use 'unusual' antibiotics such as polymyxins, isepamicin, minocycline and sulbactam (Pfizer Inc), which has inherent activity against A baumannii. Carbapenemase inhibitors might be developed in the future, despite difficulties in choosing the range of enzymes to target and obtaining broad-spectrum inhibition. For now, the best pharmaceutical strategy seems to lie in the development of novel antimicrobial classes with anti-Gram-negative activity, rather than in overcoming carbapenemases directly.     

鲍曼不动杆菌耐药机制文献计量分析

目的：利用文献计量学的方法对鲍曼不动杆菌（Ab）耐药机制的相关文献进行统计分析,以便指导临床合理用药。方法：检索PubMed、Embase、SCI英文数据库,对鲍曼不动杆菌耐药机制的相关文献进行汇总,对纳入研究的文献年份分布、作者、语种、文章类型、药物类型等进行统计分析。结果：纳入研究的文献共计2061篇,文献数量呈逐年递增趋势。其中,研究最多的药物是亚胺培南;对于碳青霉烯类抗菌药物的耐药机制研究较多。关于耐药机制的研究,分别从基因或者蛋白等角度进行阐明.从文献发表期刊分析,微生物和抗感染领域对Ab耐药机制的关注度最高,其次为药理、药学领域。结论：碳青霉烯类耐药仍是鲍曼不动杆菌耐药研究领域的重点之一,其主要的耐药机制是产生水解碳青霉烯的β-内酰胺酶-OXA酶和金属β内酰胺酶（MBL）。     

主动外排机制介导鲍曼不动杆菌多重耐药研究进展

鲍曼不动杆菌是医院感染和机会感染的主要致病菌之一,并且其耐药性高,常发生泛耐药或多重耐药。主动外排机制在细菌多重耐药发生中起着重要的作用。与鲍曼不动杆菌多重耐药有关的外排蛋白主要有AdeABC、AdeIJK、Tet（A）、Tet（B）和AheM外排泵。本文结合当前主动外排机制研究进展,对与鲍曼不动杆菌多重耐药有关的主动外排蛋白的分类、组成、基因表达调控以及耐药情况进行综述。通过对鲍曼不动杆菌主动外排机制的深入研究,对新型抗菌药物的开发和治疗方法的改进有着极大的推动作用。     

Emergence of resistance to carbapenems in Acinetobacter baumannii in Europe: clinical impact and therapeutic options

Despite having a reputation of low virulence, Acinetobacter baumannii is an emerging multidrug-resistant (MDR) pathogen responsible for community- and hospital-acquired infections that are difficult to control and treat. Interest in this pathogen emerged about one decade ago because of its natural MDR phenotype, its capability of acquiring new mechanisms of resistance and the existence of nosocomial outbreaks. Recent advances in molecular biology, including full genome sequencing of several A. baumannii isolates, has led to the discovery of the extraordinary plasticity of their genomes, which is linked to their great propensity to adapt to any environment, including hospitals. In this context, as well as the increasing antimicrobial resistance amongst A. baumannii isolates to the last-line antibiotics carbapenems and colistin, therapeutic options are very limited or absent in some cases of infections with pandrug-resistant bacteria. However, a large proportion of patients may be colonised by such MDR bacteria without any sign of infection, leading to a recurrent question for clinicians as to whether antibiotic treatment should be given and will be effective in the presence of resistance mechanisms. The worldwide emergence of A. baumannii strains resistant to colistin is worrying and the increasing use of colistin to treat infections caused by MDR bacteria will inevitably increase the recovery rate of colistin-resistant isolates in the future. Current knowledge about A. baumannii, including biological and epidemiological aspects as well as resistance to antibiotics and antibiotic therapy, are reviewed in this article, in addition to therapeutic recommendations.     

c-di-GMP protects against intranasal Acinetobacter baumannii infection in mice by chemokine induction and enhanced neutrophil recruitment

Acinetobacter baumannii has emerged as a major cause of both community-associated and nosocomial infections worldwide. A. baumannii rapidly develops resistance to multiple antibiotics; as a result, infections by this pathogen have become increasingly difficult to treat. In this study, we evaluated the effect of 3',5'-cyclic diguanylic acid (c-di-GMP), a bacterial second messenger and immunomodulator, in the host defense against A. baumannii infection in a mouse model of intranasal infection. Our results showed that 50 μg of c-di-GMP administered 18 h prior to infection provided the best protection against intranasal infection with A. baumannii. Mechanistically, administration of c-di-GMP induced the production of chemokines KC, MCP-1, MIP-1α, MIP-2 and RANTES, and enhanced neutrophil recruitment in the lung. Moreover, depletion of neutrophils abolished the protective role of c-di-GMP. Taken together, our data suggest that c-di-GMP confers resistance against intranasal A. baumannii infection in mice through a neutrophil-dependent mechanism and that c-di-GMP should be further explored as an immunomodulator for the treatment of A. baumannii infection.     

31例鲍曼不动杆菌对碳青霉烯类抗生素的耐药分析及基因型研究

目的通过对我院住院患者的31株鲍曼不动杆菌对耐碳青霉烯类抗生素的药物敏感试验及对碳青霉烯酶基因的分析研究,为临床用药提供参考依据。方法用梅里埃细菌分析仪对细菌鉴定,并对细菌进行药敏试验,同时用碳青霉烯酶4种基因的特异性引物进行基因扩增和基因型的测序分析,再对基因类型与网上GemBank比对,确定编码酶基因的类型。结果 31株鲍曼不动杆菌对多粘菌素B、丁胺卡那霉素、左旋氧氟沙星的耐药率分别为4%、20%、50%。对哌拉西林/他唑巴坦、庆大霉素的耐药率分别为80%、85%。对本试验研究的其他9种抗菌药物的耐药率均在90%以上。携带OXA-51基因有21株(68%),携带D类碳青霉烯酶OXA-23基因有26株(84%),对OXA-24、OXA-58基因引物PCR扩增结果为阴性,并随机各抽取5株OXA-23基因为阳性菌株进行测序,并通过在网上GemBank对比,结果 OXA-23标准株有99%同源,OXA-51基因阳性的菌株与OXA-51标准株97%同源。结论多粘菌素B、丁胺卡那霉素、左旋氧氟沙星对耐碳青霉烯类抗生素的鲍曼不动杆菌的敏感性较好,对其他抗生素有较强的耐药性。基因类型上以携带OXA-23型碳青霉烯酶基因为主,应合理地选用抗生素,防止多重耐药现象产生,对控制院感和疾病的疗效有极其重要意义。     

不同碳青霉烯酶酶型肠杆菌科细菌感染的治疗策略研究

摘要：目的 探讨表达不同碳青霉烯酶的耐碳青霉烯类肠杆菌科细菌(CRE)治疗策略,为临床有效治疗CRE感染提供依据。方法 回顾性分析我院2016年1月—2018年12月临床标本中分离的CRE的相关资料及药敏数据。复苏碳青霉烯耐药的肺炎克雷伯菌、大肠埃希菌和弗氏柠檬酸杆菌,PCR检测其携带的碳青霉烯耐药基因,并比较碳青霉烯酶表型试验与基因结果的一致性。采用肉汤稀释法检测替加环素和头孢他啶/阿维巴坦的敏感性,K-B法检测氨曲南和头孢他啶/阿维巴坦联合作用效果。结果 CRE对常用抗生素具有较高的耐药性。128株CRE菌株均含碳青霉烯耐药基因,其中81株含blaKPC,37株含blaNDM,5株含blaIMP,5株同时含blaKPC和blaNDM。酶抑制剂增强试验能够准确检测各种碳青霉烯酶酶型。替加环素的敏感率为97.6%,头孢他啶/阿维巴坦对产丝氨酸酶菌株的敏感率为100%,而对产金属酶和双酶菌株无效。氨曲南和头孢他啶/阿维巴坦有协同作用,对产金属酶和双酶菌株有很强的抗菌活性。结论 不同酶型CRE可考虑采用不同治疗策略,利用酶抑制剂增强试验确定酶型后,合理选择抗生素进行有效治疗。     

中国西部地区多重耐药鲍曼不动杆菌的耐药及分布特点

目的 探讨中国西部地区多重耐药鲍曼不动杆菌的分布和耐药情况,为预防和控制医院感染,合理使用抗生素提供 依据。方法 回顾性分析2016—2017年,中国西部地区10家三甲医院微生物实验室细菌培养中多重耐药鲍曼不动杆菌的分离情 况、分布及耐药性特点;数据统计及药敏分析采用WHONET 5.6软件。结果 2016—2017年送检菌株共检出鲍曼不动杆菌8847 株,检出率7.43%,其中多重耐药鲍曼不动杆菌5768株,检出率4.84%,占检出鲍曼不动杆菌的65.20%;多重耐药鲍曼不动杆 菌主要分离自呼吸道标本(80.97%)、分泌物(6.12%)及血液(2.08%),科室分布以重症监护室(14.6%)、急诊科(11.94%)、呼吸科 (11.62%)为主;在多重耐药鲍曼不动杆菌感染患者中,70岁以上的患者最多,共1688例(29.26%),明显多于其他年龄段;多重耐 药鲍曼不动杆菌对12种常用抗菌药物的耐药性普遍较高,其中有7种大于90%,耐药率最低的是阿米卡星为55.7%,其次是妥布 霉素与复方磺胺甲噁唑,分别为67.40%和68.25%。结论 中国西部地区多重耐药鲍曼不动杆菌感染问题仍然十分严重,尤其是 碳青霉烯类耐药菌,且分布及耐药性与其他地区相比具有一定的差异性;多重耐药鲍曼不动杆菌感染经验治疗可首先考虑选用 阿米卡星,其次是复方磺胺甲噁唑和妥布霉素。各地区医院应加强监测,督促临床根据药敏结果合理使用抗生素,减少多重耐 药鲍曼不动杆菌的产生,其次各医院实验室要进一步加强对多重耐药鲍曼不动杆菌的系统性分析研究,为临床及医院感染提供 更加科学有效的实验室数据。