多重耐药鲍曼不动杆菌流行病学及耐药机制的调查研究

目的调查我院鲍曼不动杆菌的流行情况、临床分布特征及其耐药性,并对其耐药表型及基因型进行分析,研究β-内酰胺酶基因及I型整合子携带情况,为本地区治疗及预防鲍曼不动杆菌的流行提供实验室依据。方法收集临床标本中检出的66株鲍曼不动杆菌株病原菌,用纸片扩散法（K-B法）测定鲍曼不动杆菌对18种抗生素的敏感性。PCR扩增分析β-内酰胺酶基因、整合子基因。结果鲍曼不动杆菌主要分离自ICU及呼吸内科病房,标本以来源于呼吸道标本最为常见。大多数菌株显示出多重耐药性,对第三代头孢菌素、氨曲南、复方新诺明、哌拉西林、环丙沙星耐药率较高,对亚胺培南及含酶抑制剂较敏感。I型整合子基因的检出率为54.5%。结论鲍曼不动杆菌是一种多重耐药菌,可普遍存在于医院环境中,亚胺培南和含酶抑制剂可作为该菌感染的治疗药物。β-内酰胺酶基因及I型整合子基因是导致鲍曼不动杆菌多重耐药的主要原因。     

鲍曼不动杆菌Ⅰ类整合子与多重耐药相关性研究

目的 了解临床分离鲍曼不动杆菌的耐药状况、Ⅰ类整合子的分布情况,探讨Ⅰ类整合子与多重耐药的关系.方法 检测20种临床常用抗菌药物对鲍曼不动杆菌临床分离株的最低抑菌浓度(MIC).PCR扩增Ⅰ类整合酶基因.对部分Ⅰ类整合酶阳性菌株进行耐药基因盒序列分析.结果 鲍曼不动杆菌呈现多重耐药,鲍曼不动杆菌对IMP和MRP耐药率分别为0.9%和1.8%,对CPZ/SB的耐药率为35.7%,对其它抗菌药物的耐药率均大于60%,多重耐药率为76.8%(86/112),但对COL和MIN均敏感.80.4%(90/112)的菌株检测出Ⅰ类整合子.Ⅰ类整合子阳性株对多种药物的耐药率均高于阴性株,且Ⅰ类整合子阳性株多重耐药率(90%)明显高于阴性株(22.7%)(P<0.01).Ⅰ类整合子基因盒序列分析显示,Ⅰ类整合子携带aacA4,catB8和aadA13种耐药基因.结论 Ⅰ类整合子在鲍曼不动杆菌中检出率很高并与其多重耐药性关系密切.     

该基因的整合和鲍曼不动杆菌基因可变区盒式结构分析检测

目的:了解整合酶基因在天津地区多重耐药鲍曼不动杆菌株中的分布和流行情况,分析整合子与鲍曼不动杆菌多重耐药性的关系。方法:收集天津地区3家医院55株多重耐药鲍曼不动杆菌,以K-B法进行抗生素敏感试验,用PCR方法检测整合酶基因,结合以往检测的耐药基因,采用聚类法对55株多重耐药鲍曼不动杆菌进行菌株亲缘性分析。结果:55株多重耐药鲍曼不动杆菌共检出47株含有Ⅰ类整合酶基因,其中有23株检出可变区结构,未检出Ⅱ、Ⅲ类整合酶基因,可变区所携带的aacA4和aadA1基因盒是引起鲍曼不动杆菌对氨基糖苷类抗生素耐药的主要原因。55株多重耐药鲍曼不动杆菌共含有3个克隆株。结论:天津地区多重耐药鲍曼不动杆菌中主要存在Ⅰ类整合子,聚类分析方法可对所有菌株分型。     

鲍曼不动杆菌感染的分布特点及耐药性分析

目的 了解福建省莆田学院附属医院3年来鲍曼不动杆菌感染现状,分析其耐药谱变迁,为临床合理使用抗生素提供依据.方法 对该院2008~2010年分离的鲍曼不动杆菌分离情况及抗菌药物敏感性进行回顾性的分析.结果 3年间共分离鲍曼不动杆菌628株,其中通过呼吸道感染的占90.76%,每年分离率均占总分离菌的前三位.鲍曼不动杆菌对常用抗菌药物的耐药率有普遍上升趋势并呈多重耐药,其中对头孢哌酮/舒巴坦的耐药率最低(16.24%),对亚胺培南的耐药率也较低(42.83%),对氨基糖苷类、氟喹诺酮类、头孢菌素类等的耐药率在59.87%~86.94%.结论 鲍曼不动杆菌临床分离率不断激增,耐药性逐年增强,应加强其耐药率监测,合理使用抗生素.     

某三甲医院2012-2015年抗菌药物使用强度与鲍曼不动杆菌耐药性的相关性分析

目的 通过对某三甲医院2012-2015年抗菌药物的使用强度与鲍曼不动杆菌对临床常用的各类抗菌药物的耐药性分析,探讨抗菌药物使用强度与鲍曼不动杆菌耐药性之间的关系,为临床合理用药提供参考依据.方法 回顾性调查某三甲医院2012-2015年住院病人常用抗菌药物的用药频度和用药强度,并统计鲍曼不动杆菌对常用抗菌药物的耐药率,利用SPSS 21.0统计软件进行相关性数据分析.结果 鲍曼不动杆菌对头孢哌酮/舒巴坦的耐药率与β-内酰胺类/β-内酰胺酶抑制剂的使用强度呈正相关(r=1,P<0.01),多重耐药鲍曼不动杆菌检出率与头孢哌酮/舒巴坦的使用强度呈显著正相关(r=1,P<0.01).结论 合理控制β-内酰胺类/β-内酰胺酶抑制剂的使用,在一定程度上可减缓鲍曼不动杆菌耐药的产生.     

2009-2014年我院抗菌药物临床应用对鲍曼不动杆菌耐药性变迁的影响

目的 研究鲍曼不动杆菌耐药性变迁趋势,探讨抗菌药物使用对鲍曼不动杆菌耐药率变化的影响,为临床合理使用抗菌药物提供理论依据.方法 回顾性分析2009-2014年鲍曼不动杆菌耐药率变化趋势及抗菌药物年用量,计算用药频度(DDDs),采用Pearson相关分析法对耐药率与DDDs进行分析.结果 2 859株鲍曼不动杆菌菌株对常用抗菌药物呈多重耐药趋势,对β-内酰胺类、大多β-内酰胺类加酶抑制剂、氨基糖苷类、喹诺酮类、碳青霉烯类、磺胺类的耐药率均超过65.0％,仅对头孢哌酮/舒巴坦和米诺环素的耐药率相对较低,波动在32.1％ ～ 54.2％之间.2009-2014年不同抗菌药物的DDDs有不同程度升降.庆大霉素、头孢吡肟、左氧氟沙星和亚胺培南的DDDs与鲍曼不动杆菌耐药率呈高度正相关(r＞0.800,P＜0.05).结论 鲍曼不动杆菌对常用抗菌药物耐药性较为严重,抗菌药物用量与鲍曼不动杆菌耐药率之间存在一定相关性,应加强抗菌药物临床应用管理.     

鲍曼不动杆菌的耐药性及与Ⅰ型整合子的关系

目的分析河北省临床分离的90株鲍曼不动杆菌的耐药情况及与Ⅰ型整合子的关系。方法用微量肉汤稀释法测定美罗培南等7种临床常用抗菌药物的最小抑菌浓度,PCR检测Ⅰ型整合子基因,并分析耐药性与Ⅰ型整合子基因的关系。结果 90株鲍曼不动杆菌中,多重耐药株56株（62.2%）;56株Ⅰ型整合子基因阳性;Ⅰ型整合子阳性菌株对多种药物耐药,整合子阴性菌株耐药种类较少（P（0.05）。结论临床常用的7种抗菌药物中,无一种能完全抑制鲍曼不动杆菌,其中美罗培南和亚胺培南敏感率较高,而头孢他啶和阿米卡星耐药率较高;Ⅰ型整合子基因的作用是导致鲍曼不动杆菌多重耐药和高耐药的重要原因之一。     

2013年鲍曼不动杆菌临床分布及耐药性分析

目的:通过持续监测鲍曼不动杆菌临床分布特点及耐药性,为临床鲍曼不动杆菌导致的感染性疾病诊断与合理用药提供理论依据. 方法:对2013年1~12月泉州市第一医院临床送检标本进行常规细菌分离培养和鉴定,统计分析鲍曼不动杆菌临床分布及耐药性. 结果:鲍曼不动杆菌在送检标本中主要来源于痰液(38.92%),其次是血液(18.87%)等,耐药性严重,头孢哌酮/舒巴坦耐药率高达42.3%,对庆大霉素、哌拉西林等其余12种常用抗菌药物耐药性均大于70.00%. 结论:鲍曼不动杆菌耐药情况较为严重,耐药谱不断发生改变. 在临床用药的选择上,应尽量降阶梯使用,选择耐药率低的抗菌药物. 做到个体化合理给药,及时控制感染,提高疗效.     

鲍曼不动杆菌整合子阳性与多重耐药的相关性研究

目的在鲍曼不动杆菌中检测1~3类整合子,并分析整合子对细菌多重耐药性的影响。方法用琼脂二倍稀释法测定24种抗菌药物对临床分离68株鲍曼不动杆菌的抗菌活性,用聚合酶链反应进行整合子的初筛,对整合子阳性的菌株进行测序,并分析其多重耐药性。结果在68株临床分离多重耐药鲍曼不动杆菌中,发现19株I类整合子阳性,占27.9%;未检测到II、III类整合子。整合子阳性菌株对青霉素类(哌拉西林)、头孢菌素类(头孢噻肟、头孢哌酮、头孢曲松、头孢他啶、头孢吡肟)、氨基糖苷类、四环素类均呈现出高度耐药为86.7%~100%;对第3代头孢菌素类(头孢噻肟、头孢哌酮、头孢曲松)为100%耐药;对β内酰胺酶抑制剂复合制剂耐药率也达82.5%以上。比较整合子阳性与整合子阴性鲍曼不动杆菌耐药性,发现对氨基糖苷类、磺胺类抗菌药物耐药率差异有统计学意义。结论鲍曼不动杆菌耐药性严重,I类整合子广泛地存在于鲍曼不动杆菌中,I类整合子阳性菌株对氨基糖苷类、磺胺类抗菌药物的耐药率大于整合子阴性的菌株,提示整合子对细菌耐药性的播散有重要作用。     

145例鲍曼不动杆菌的临床分布及耐药性分析

目的了解本院鲍曼不动杆菌的临床分布及对抗菌药物的耐药性。方法对本院2012年至2014年分离的145株不重复鲍曼不动杆菌进行鉴定及药敏试验,药敏试验采用MIC法,结果按CLSI 2010年版标准判断其敏感性。结果鲍曼不动杆菌主要来源于临床各种标本,尤其是肺部感染重要的病原菌。鲍曼不动杆菌对多类抗菌药物均表现出较高的耐药率,其中检出多重耐药鲍曼不动杆菌(MDR-AB)27株,占检出的鲍曼不动杆菌的18.6%。结论鲍曼不动杆菌是引起肺部及其他部位感染的主要致病菌之一,并且,鲍曼不动杆菌存在严重的耐药性,临床应对感染进行细菌培养和耐药性监测,合理用药。     

Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply “precision medicine” to antimicrobial chemotherapy?

Introduction: For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae.

Areas covered: We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered ‘old’ antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containig a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration.

Expert opinion: Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches should be the new paradigm in treating infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic.     

鲍曼不动杆菌的耐药性分析

目的了解鲍曼不动杆菌的分布及耐药情况，为临床合理使用抗生素提供依据。方法细菌鉴定采用APIStaph和TH-168鉴定编码管，K—B法进行药敏试验。结果169例鲍曼不动杆菌对10种抗生素的耐药率为：亚胺培南（3％）、头孢哌酮舒巴坦（5％）、氨苄西林舒巴坦（20％）、阿米卡星（35％）、环丙沙星（40％）、头孢他啶（42％）、庆大霉素（52％）、哌拉西林（56％）、头孢哌酮（65％）、氨苄西林（88％）。结论加强对鲍曼不动杆菌的耐药性监测，根据药敏结果结合临床合理使用抗生素。     

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。     

Principles of appropriate antibiotic use

Many antibiotics, including macrolides and quinolones, are used incorrectly in the treatment of presumed respiratory tract infections. The use of broad-spectrum antibiotics increased considerably in the 1990s, but often this use is inappropriate. Guidelines, such as those for community-acquired pneumonia, encourage rational therapy and more prudent prescribing. There are strong links between appropriate use, compliance and resistance as well as between regimen complexity and compliance. These issues provide a platform for thinking about a short-duration, high-compliance drug therapy with good clinical efficacy. Such therapy will need to be combined with programs to promote rational antibiotic use, particularly targeting inappropriate prescribing for viral infections and use of agents with a broader antimicrobial spectrum than is necessary.     

Practical applications and feasibility of efflux pump inhibitors in the clinic--a vision for applied use

The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drug targets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination drug should exhibit increased potency, enhanced spectrum of activity and reduced propensity for acquired resistance. To date, at least one class of broad-spectrum EPI has been extensively characterized. While these efforts indicated a significant potential for developing small molecule inhibitors against efflux pumps, they did not result in a clinically useful compound. Stemming from the continued clinical pressure for novel approaches to combat drug resistant bacterial infections, second-generation programs have been initiated and show early promise to significantly improve the clinical usefulness of currently available and future antibiotics against otherwise recalcitrant Gram-negative infections. It is also apparent that some changes in regulatory decision-making regarding resistance would be very helpful in order to facilitate approval of agents aiming to reverse resistance and prevent its further development.     

Efflux systems in bacterial pathogens: an opportunity for therapeutic intervention? An industry view

The efflux systems of bacteria protect cells from antibiotics and biocides by actively transporting compounds out of the cytoplasm and/or periplasm and thereby limit their steady-state accumulation at their site(s) of action. The impact of efflux systems on the efficacy of antibiotics used in human medicine and animal husbandry is becoming increasingly apparent from the characterization of drug-resistant strains with altered drug efflux properties. In most instances, efflux-mediated antibiotic resistance arises from mutational events that result in their elevated expression and, in the case of efflux pumps with broad substrate specificity, can confer multi-drug resistance (MDR) to structurally unrelated antibiotics. Knowledge of the role of efflux systems in conferring antibiotic resistance has now been successfully exploited in the pharmaceutical industry and contributed, in part, to the development of new members of the macrolide and tetracycline classes of antibiotics that circumvent the efflux-based resistance mechanisms that have limited the clinical utility of their progenitors. The therapeutic utility of compounds that inhibit bacterial drug efflux pumps and therein potentiate the activity of a co-administered antibiotic agent remains to be validated in the clinical setting, but the approach holds promise for the future in improving the efficacy and/or extending the clinical utility of existing antibiotics. This review discusses the potential of further exploiting the knowledge of efflux-mediated antibiotic resistance in bacteria toward the discovery and development of new chemotherapeutic agents.     

危重患者多重耐药鲍曼不动杆菌感染的药学监护分析

目的:探讨临床药师对多重耐药鲍曼不动杆菌感染的危重患者实施药学监护的特点。方法:回顾性分析36例危重患者感染多重耐药鲍曼不动杆菌的病原菌分布、细菌耐药情况、治疗结果及进行药学监护的情况。结果:多重耐药鲍曼不动杆菌耐药情况严重,危重患者感染后治疗困难。结论:临床药师应深入临床,发挥药学专长,加强药学监护,参与危重患者多重耐药鲍曼不动杆菌感染治疗方案的制订,这对于抗感染药物的合理应用,防止耐药菌株产生是非常重要的。     

医院感染常见革兰阴性菌的临床分布及耐药性分析

目的以了解医院感染革兰阴性菌的临床分布及耐药特点,为临床抗菌药物的应用提供依据。方法对2010年²012年我院常见的医院感染革兰阴性菌的临床分布及耐药性进行回顾性分析。结果在医院感染细菌前5位的革兰阴性菌为大肠埃氏菌、肺炎克雷伯氏菌、铜绿假单胞菌、鲍氏不动杆菌、奇异变形杆菌、其次是产气肠杆菌、阴沟肠杆菌、食麦芽假单胞菌。细菌均呈现多耐药趋势,临床常用的第一、二、三代头孢菌素类、单环内酰胺类、头霉素类、部分β-内酰胺酶抑制剂由于细菌产ESBLs及Amp C而发生耐药,第四代头孢吡肟耐药率也达50%2012年我院常见的医院感染革兰阴性菌的临床分布及耐药性进行回顾性分析。结果在医院感染细菌前5位的革兰阴性菌为大肠埃氏菌、肺炎克雷伯氏菌、铜绿假单胞菌、鲍氏不动杆菌、奇异变形杆菌、其次是产气肠杆菌、阴沟肠杆菌、食麦芽假单胞菌。细菌均呈现多耐药趋势,临床常用的第一、二、三代头孢菌素类、单环内酰胺类、头霉素类、部分β-内酰胺酶抑制剂由于细菌产ESBLs及Amp C而发生耐药,第四代头孢吡肟耐药率也达50%⁶0%,耐碳青霉烯类鲍氏不动杆菌由于碳青霉烯类抗菌药物的使用强度增加而显著增加,我院美罗培南、亚胺培南耐药率逐年明显上升已接近60%。而氨基糖苷类中的阿米卡星除鲍曼氏不动杆菌外由于近期少用使敏感性有所提高。结论分析医院感染常见感染细菌分布及耐药性,对指导临床合理应用抗菌药物及预防和控制耐药菌在医院内传播有着重要意义。     

Management of cSSTIs:the role of daptomycin

ABSTRACT

Background: Skin and soft tissue infections (SSTIs) and complicated SSTIs (cSSTIs), particularly those caused by Gram-positive pathogens, are among the most common human bacterial infections The emergence of resistance to antibiotics such as methicillin and vancomycin has compromised treatment options for these infections and stimulated the search for new antimicrobial therapies. Daptomycin, the first in a class of agents known as cyclic lipopeptides, is a novel antibiotic with potent activity against most Grampositive pathogens, including methicillin‐ resistant Staphylococcus aureus.

Scope: This review examines the novel properties of daptomycin and describes its therapeutic efficacy and tolerability, particularly in the treatment of cSSTIs. The data search strategy included identification of original research papers, review articles, meeting reports and editorials by searches of MEDLINE and references from relevant articles.

Findings: In vitro studies have demonstrated that daptomycin has superior bactericidal activity compared with vancomycin and the newer anti-Gram-positive agents, quinupristin/dalfopristin and linezolid. Robust, randomised, phase III clinical trials have shown daptomycin to be effective and well tolerated for the treatment of cSSTIs caused by Gram-positive bacteria, with equivalent clinical success rates and a similar safety profile to those of comparator agents. Data from these studies suggest a trend toward shorter duration of therapy and faster resolution of symptoms with daptomycin.

Conclusions: Given the pressing need for new antibiotics to combat infections caused by Gram-positive organisms, and to overcome the problem of resistance to conventional antibiotics, daptomycin is a welcome addition to the treatment options for the management of cSSTIs.