2016—2017年儿童碳青霉烯类耐药肠杆菌科细菌的分布特点和耐药性分析

目的 了解我国儿童人群中碳青霉烯类耐药肠杆菌科细菌(CRE)分布及耐药现状,为临床合理使用抗菌药物提供依据。 方法 收集2016年1月1日至2017年12月31日国内10所三级甲等儿童医院的临床分离株,采用纸片扩散法(KB法)和仪器法对CRE菌株进行药敏试验,根据美国临床实验室标准化协会(CLSI)2017年版标准判断结果。采用WHONET 5.6统计分析软件对菌株分布特点和耐药性进行回顾性分析。 结果 共收集3 065株CRE临床分离株,总体检出率为7.7%,新生儿组检出率(13.5%)较非新生儿组(5.8%)高,2017年CRE检出率较2016年呈上升趋势(9.7% vs 5.7%)。3 065株CRE分离株前5位分别是肺炎克雷伯菌1 912株(62.0%)、大肠埃希菌667株(22.0%)、阴沟肠杆菌206株(7.0%)、产气克雷氏菌(56株,1.8%)、黏质沙雷菌(47株,1.5%)。主要分布科室为新生儿科[含新生儿重症监护室(NICU),44.8%]、重症监护室(ICU,19.7%)。呼吸道标本(61.8%)、尿液标本(19.4%)、血液标本(5.7%)是CRE分离株的主要来源。药敏结果显示,CRE菌株对亚胺培南、美罗培南、厄他培南等碳青霉烯类抗菌药物以及青霉素类、大多数头孢菌素类呈高度耐药(79.6%～100%),其中新生儿组耐药程度更高( P<0.05),另外儿童对阿米卡星(19.7%)、磷霉素(11.9%)等氨基糖苷类,左氧氟沙星(37.7%)、环丙沙星(43.3%)等氟喹诺酮类,替加环素(3.8%)等耐药率相对较低,目前未分离到多黏菌素B耐药株。 结论 2017年CRE常见菌种检出率较2016年均有不同程度的上升,新生儿较其他儿童检出率更高,且对临床常见抗菌药物耐药形势更为严峻,应引起高度重视并及时采取措施。     

碳青霉烯类耐药肠杆菌科细菌实验室检测的研究

目前碳青霉烯类耐药肠杆菌科细菌（CRE）在世界各地已呈广泛流行的趋势,特别是碳青霉烯酶的扩散严重威胁着公共健康。临床微生物实验室如何选择适合的检测方法,从而出具及时准确的报告对于防控耐药菌株的传播以及指导临床医生用药具有重要的价值。本文就耐药机制及表型、基因型以及酶免疫层析技术三大类CRE检测方法进行综述。     

肠杆菌科细菌产碳青霉烯酶研究进展

碳青霉烯类抗生素抗菌谱广,抗菌活性强,杀菌作用快,尤其适用于治疗由产超广谱β内酰胺酶(ESBLs)或(和)头孢菌素酶(AmpC)细菌所引起的严重感染.既往临床上常见的耐碳青霉烯类抗生素菌株为以绿脓假单胞菌和不动杆菌属细菌为代表的非发酵细菌,但随着碳青霉烯类抗生素在临床上的广泛使用,耐碳青霉烯类抗生素的肠杆菌科菌株逐渐增加,给临床治疗带来了极大困难.肠杆菌科细菌对碳青霉烯类抗生素耐药的主要机制为产生碳青霉烯酶,现回顾近年的相关研究,就肠杆菌科细菌产碳青霉烯酶的研究进展及其检测方法、耐药菌株的治疗等做一综述.     

碳青霉烯类耐药肠杆菌科细菌实验室检测的研究

碳青霉烯类耐药肠杆菌科细菌（CRE）已经成为全球性公共卫生问题,这类细菌往往伴随高致病率、高致残率、高死亡率,为临床治疗带来了极大的挑战。CRE的耐药机制主要是产生碳青霉烯酶。快速、准确地检测产碳青霉烯酶的肠杆菌科细菌,对于合理使用抗生素,预防和控制产酶菌株的传播具有重要意义。本文就实验室检测肠杆菌科细菌产碳青霉烯酶的研究方法进展作一综述。     

碳青霉烯耐药肠杆菌目细菌耐药性及耐药传播机制研究

目的:探讨碳青霉烯耐药肠杆菌目细菌(CRE)的耐药性及耐药传播机制,为CRE感染的治疗和防控提供科学依据。方法:收集绍兴第二医院2016年5月—2018年8月临床分离的CRE 76株。采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)进行菌种鉴定;微量肉汤稀释法或琼脂稀释法测定多黏菌素、替加环素、头孢他啶...     

碳青霉烯耐药肠杆菌目细菌耐药性及耐药传播机制研究

目的 探讨碳青霉烯耐药肠杆菌目细菌(CRE)的耐药性及耐药传播机制,为CRE感染的治疗和防控提供科学依据。 方法 收集绍兴第二医院2016年5月—2018年8月临床分离的CRE 76株。采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)进行菌种鉴定;微量肉汤稀释法或琼脂稀释法测定多黏菌素、替加环素、头孢他啶/阿维巴坦和磷霉素等10种抗菌药物的最低抑菌浓度(MICs);PCR法筛查碳青霉烯酶编码基因( bla _KPC、 bla _NDM、 bla _IMP、 bla _VIM、 bla _OXA-48)并测序确认;脉冲场凝胶电泳(PFGE)和多位点序列分型(MLST)分析菌株的同源性;S1-PFGE联合Southern blot印迹杂交技术进行碳青霉烯酶基因定位;滤膜接合试验明确携带碳青霉烯酶基因质粒的水平转移能力。 结果 76株CRE中,肺炎克雷伯菌51株,大肠埃希菌10株,其他肠杆菌目细菌15株;主要分离自尿、痰及血液标本;ICU的分布率最高(55.26%)。76株CRE对多黏菌素、替加环素和头孢他啶/阿维巴坦呈现较低耐药率(0%、1.33%、18.42%),对阿米卡星和磷霉素的耐药率均<45%,对其他药物的耐药率均>97%。KPC-2型碳青霉烯酶的检出率最高(85.33%)。产KPC-2的ST11型CRKP占比最高(62.75%),主要分布在ICU(62.50%)。Southern blot杂交试验显示 bla _KPC-2主要位于约90 kb的质粒上(39/63)。滤膜接合试验显示 bla _KPC、 bla _NDM和 bla _IMP均可通过质粒水平转移给受体菌。 结论 该院CRE仅对多黏菌素、替加环素、头孢他啶/阿维巴坦等少数抗菌药物呈现较好敏感性;产KPC-2型碳青霉烯酶是肠杆菌目细菌对碳青霉烯类抗生素耐药的主要原因;产KPC-2的ST11型肺炎克雷伯菌是碳青霉烯耐药肺炎克雷伯菌(CRKP)的主要流行克隆;90 kb大小的质粒是编码 bla _KPC-2基因的主要质粒类型;碳青霉烯酶基因可通过质粒水平传播;医院需加强医院感染预防控制措施,控制CRE的克隆流行。     

碳青霉烯类耐药肠杆菌科细菌分布与流行特征研究进展

碳青霉烯类耐药肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)是指对任何一种碳青霉烯类抗菌药物耐药的肠杆菌科细菌。作为引起各类感染最常见的病原,肠杆菌科细菌广泛分布在全球各个地区,并且经常引起医疗机构内或区域性的大范围暴发传播。随着此类细菌对临床常用抗感染药物耐药性的增加,越来越多的药物无法控制此类感染,给医疗结构的医院感染控制和抗感染治疗带来巨大挑战。CRE的出现和传播就在此过程中发挥重要作用。了解CRE的分布与传播规律对于控制此类病原的传播具有重要意义,本文就CRE的分布与流行特征研究进展进行综述。近年来,全球范围内临床分离CRE的主要种类是产KPC肺炎克雷伯菌。此类菌株最早在美国被分离到,之后产KPC-2和KPC-3菌株在多地区广泛传播。2010年NDM-1分离自印度和英国的大肠埃希菌和肺炎克雷伯菌,此后在全球各个地区均有检出,成为KPC以外肠杆菌科细菌中第二类常见的碳青霉烯酶。OXA-48在2004年自一株对碳青霉烯耐药的肺炎克雷伯菌中首次检出,对碳青霉烯类抗菌药物具有比较弱的水解活性。产OXA-48肠杆菌在土耳其、西班牙、摩洛哥、突尼斯等国家发生过较大规模暴发流行。在我国,CRE的主要种类是产KPC肺炎克雷伯菌,并以ST11型菌株为主要流行序列型(sequence type,ST)。此外,也有产KPC的产酸克雷伯菌、大肠埃希菌、阴沟肠杆菌、费劳地枸橼酸杆菌、黏质沙雷菌、奇异变形杆菌、河生肠杆菌和摩根菌等检出的报道。我国分离到的产NDM菌种以大肠埃希菌和肺炎克雷伯菌为主,同时也发现了阴沟肠杆菌、产酸克雷伯菌、弗劳地枸橼酸杆菌、奇异变形杆菌、产气肠杆菌等携带NDM编码基因。产OXA-48肺炎克雷伯菌在我国仅有北京和台湾地区有过小规模暴发的报道。     

KPC-2及IMP-4酶介导肠杆菌科细菌碳青霉烯类耐药研究

目的 探讨我院肠杆菌科细菌对碳青霉烯类抗生素的耐药机制及其流行特点。 方法 收集杭州市富阳区第一人民医院2013年1月至2014年8月分离的对碳青霉烯类抗生素(厄他培南)敏感性下降的肠杆菌科细菌,采用K-B纸片法及E-test法进行药敏试验,改良Hodge试验、EDTA抑制试验及超广谱β-内酰胺酶(ESBLs)表型筛选试验进行耐药表型筛选;采用PCR法及测序技术检测耐药基因、KPC基因周围序列和肺炎克雷伯菌7个管家基因,多位点序列分型进行7个管家基因的序列分析;运用PFGE对鉴定为同一菌种的细菌进行同源性分析;采用S1-PFGE联合Southern杂交对已明确的碳青霉烯耐药基因进行基因定位。 结果 共收集到19株厄他培南敏感性下降的肠杆菌科细菌,所有菌株呈多重耐药现象,且同一菌株常携带有多种耐药基因,其中 bla _KPC-2、 bla _IMP-4、 bla _SHV-1、 bla _CTX-M-65、 bla _CTX-M-15、 bla _TEM-1、 rmtB为最常见共同携带的耐药基因。PFGE结果提示14株肺炎克雷伯菌呈多克隆分布,MLST分型以ST11型为主。11株肺炎克雷伯菌和1株大肠埃希菌产KPC-2酶, bla _KPC-2基因分别定位于4种大小不同的质粒上(大小分别约为95 kb、140 kb、200 kb及240 kb),所有菌株 bla _KPC-2周围基因结构从上游至下游均为IS Kpn8、 bla _KPC-2和IS Kpn6- like元件;1株产酸克雷伯菌和1株肺炎克雷伯菌产IMP-4型碳青霉烯酶, bla _IMP-4基因定位于大小约为300 kb的质粒上。 结论 KPC-2型及IMP-4型碳青霉烯酶是造成我院肠杆菌科细菌对碳青霉烯类抗生素耐药的主要原因;我院碳青霉烯类耐药肺炎克雷伯菌(CRKP)菌株呈多克隆散在播散的流行特点,未发现优势克隆。     

某传染病医院耐碳青霉烯类肠杆菌科细菌的分布特点及耐药性分析

目的 探讨本院2016年1月~2020年11月耐碳青霉烯类肠杆菌科细菌（CRE）的分布及耐药性,为临床预防和治疗CRE提供参考依据。方法 回顾性分析我院2016年1月~2020年11月从临床标本中分离的112株CRE的分布及耐药性,使用法国生物梅里埃公司的VITEK-Compact Ⅱ进行细菌鉴定和药敏试验,英国OXOID纸片行扩散法（K-B法）作为药敏试验补充方法,改良Hodge试验对CRE产碳青霉烯酶情况进行确认。结果 2016年1月~2020年11月分离出112株CRE总检出率为5.62%,检出率呈逐年上升趋势;CRE菌种主要以肺炎克雷伯菌为主,其次为大肠埃希菌、阴沟肠杆菌;标本类型主要以痰液为主,其次为尿液和血液;我院感染CRE患者以≥60岁年龄为主（55.36%）。药敏试验结果显示,我院CRE菌株对替加环素的耐药率最低（4.46%）,其次为阿米卡星（13.39%）,对于其余大多数常用抗菌药物耐药率较高;CRE菌种间耐药率存在差异,尤其是耐碳青霉烯类肺炎克雷伯菌（CRKP）较其他菌种表现出更高的耐药率。结论 我院近5年CRE检出率逐年上升,且对于常用的抗菌药物耐药率较高。临床应重视对CRE的耐药性监测,尤其是对CRKP的重点防控,规范临床合理使用抗菌药物,采取综合防控措施,阻止CRE的感染和传播。     

耐碳青霉烯类药物肠杆菌科细菌耐药特点和感染危险因素分析

目的 对耐碳青霉烯类药物肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae, CRE)耐药特点和危险因素进行分析,为临床防治CRE感染提供理论依据。方法 收集本院2022年8月至2023年7月期间CRE感染患者病例信息。按病例组∶对照组为1∶2的比例选取同一时期对碳青霉烯类药物敏感肠杆菌科细菌(Carbapenem-sensitive Enterobacteriaceae, CSE)感染病例作为对照组,采用Logistic多因素回归分析CRE感染发生的独立危险因素。结果 CRE检出率为18.2%(111/611)。CRE菌株对大部分抗菌药物耐药率高于CSE组。多因素分析显示呼吸系统疾病(OR=6.330,95%CI:1.486～26.962)、低蛋白血症(OR=4.590,95%CI:1.544～13.646),使用3代头孢菌素(OR=7.981,95%CI:2.304～27.650)、青霉素类(OR=3.222,95%CI:1.040～9.984)、碳青霉烯类(OR=4.420,95%CI:1.231～15.868)以及糖肽类抗生素(OR=8.760,95%CI:1.543～49.734),留置胃管(OR=4.933,95%CI:1.180～20.627)以及住院时间≥14d(OR=4.000,95%CI:1.271～12.593)与感染CRE相关。结论 CRE检出率较高,耐药率高,基础疾病为呼吸系统疾病和低蛋白血症、使用3代头孢菌素、青霉素类、碳青霉素类、糖肽类抗生素、留置胃管和住院时间≥14d是感染CRE的独立危险因素。     

Identification and screening of carbapenemase-producing Enterobacteriaceae

Carbapenem-hydrolysing β-lactamases are the most powerful β-lactamases, being able to hydrolyse almost all β-lactams. They are mostly of the KPC, VIM, IMP, NDM and OXA-48 types. Their current extensive spread worldwide in Enterobacteriaceae is an important source of concern, as these carbapenemase producers are multidrug-resistant. Detection of infected patients and of carriers are the two main approaches for prevention of their spread. Phenotypic and molecular-based techniques are able to identify these carbapenemase producers, although with variable efficiencies. The detection of carriers still relies mostly on the use of screening culture media.     

Rapid detection of carbapenemase-producing Enterobacteriaceae from blood cultures

The biochemical-based Carba NP test has been evaluated to detect carbapenemase-producing Enterobacteriaceae (n = 193) directly from spiked blood cultures. It was able to rapidly detect KPC (n = 50), IMP (n = 27), VIM (n = 37), NDM (n = 33) and OXA-48-like producers (n = 46) with sensitivity and specificity of 97.9% and 100%, respectively. This cost-effective technique may be implemented in any microbiology laboratory and offers a reliable test for an early identification of carbapenemase-producing Enterobacteriaceae directly from blood culture that could be useful for the management of infected patients.     

儿科产超广谱β-内酰胺酶志贺菌的基因型和耐药性研究

目的 探讨儿科临床分离志贺菌产超广谱β-内酰胺酶(ESBLs)的基因型及其耐药特点.方法 收集2004年1月至2008年12月北京儿童医院细菌性痢疾住院患儿粪便标本中分离出志贺菌共59株,按照美国临床和实验室标准协会推荐的表型确证试验检测ESBLs,用琼脂稀释法进行最低抑菌浓度(MIC)测定,对产ESBLs菌株进行PCR扩增明确其基因型,对扩增产物进行DNA序列分析确定基因亚型.结果 59株志贺菌中共检出产ESBLs者21株,占35.6%.21株产ESBLs志贺菌PCR均扩增到CTX-M型ESBLs,包括CTX-M-1型6株,CTX-M-9型15株,其中有4株同时伴有TEM型酶,6株伴有OXA型酶.DNA序列分析证实6株CTX-M-1型分别为CTX-M-3亚型(1株)、CTX-M-15亚型(2株)、CTX-M-57亚型(3株),15株CTX-M-9型均为CTX-M-14亚型,伴随存在的TEM型及OXA型耐药基因分别为TEM-1型广谱酶、OXA-1型广谱酶.药敏结果显示对产ESBLs菌株敏感性较好的抗生素有亚胺培南、美罗培南、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦和头孢西丁,其耐药率均小于15%.产不同CTX-M基因亚型的菌株对头孢他啶的耐药性不同.结论 本地区儿科分离志贺菌产ESBLs阳性率高,均为CTX-M型,其中以CTX-M-14亚型为主,少部分为CTX-M-3、CTX-M-15和CTX-M-57亚型.大部分产ESBLs菌株呈多重耐药,碳青霉烯类抗生素应作为治疗产ESBLs志贺菌的首选.     

Emergence of carbapenem-resistant Enterobacteriaceae in Austria, 2001-2010

We report the emergence of carbapenem-resistant Enterobacteriaceae in Austria. Over a 10-year period, carbapenem-resistant Enterobacteriaceae isolates were obtained from 13 hospitalized patients, with the first isolation in the year 2005 and a remarkable increase in the number of involved patients in 2010. Carbapenem-resistant Enterobacteriaceae comprise eight Klebsiella pneumoniae isolates, four Klebsiella oxytoca isolates, and one Escherichia coli isolate. The detected carbapenemases were the metallo-β-lactamases New Delhi β-lactamase, VIM and IMP, and the serin-β-lactamase Klebsiella pneumoniae carbapenemase.     

Development of carbapenem resistance during therapy for non-typhoid Salmonella infection

Multidrug-resistant Salmonella infection is a global problem, and carbapenems may represent the last therapeutic choice. We report a case of infection caused by ceftriaxone-resistant and ciprofloxacin-resistant Salmonella enterica serotype Typhimurium. A bla_CMY-2-containing Tn6092, located on a self-transferable IncI1 plasmid, was found in all isolates derived from the patient. During ertapenem treatment, the strain developed carbapenem resistance. Apart from the OmpD deficiency found in all isolates, the strain further developed OmpC deficiency through a single gene mutation, and became carbapenem-resistant. Salmonella appears to be very plastic in developing antimicrobial resistance. Care must be taken by physicians when treating multidrug-resistant Salmonella infection.     

铜绿假单胞菌oprD2基因突变及表达量改变与碳青霉烯类耐药的关系

目的 研究铜绿假单胞菌外膜通道蛋白OprD2的表达减弱或缺失,以及OprD2蛋白自身突变是否会影响铜绿假单胞菌对碳青霉烯类药物的耐药性.方法 收集分离自临床对亚胺培南(IPM)的最低抑菌浓度(MIC)值≥8μg/m1的铜绿假单胞菌共101株,采用肉汤稀释法检测菌株对比阿培南(BPM)、美罗培南(MEM)、帕尼培南(PEM)的MIC值;荧光定量RT-PCR检测铜绿假单胞菌膜通道蛋白oprD2基因的表达量情况;针对oprD2相对表达量正常并对亚胺培南耐药的铜绿假单胞菌,采用普通PCR的方法扩增oprD2全长基因并测序.结果 根据铜绿假单胞菌的OprD2蛋白相对表达量结果,将101株铜绿假单胞菌分成两组,组1为OprD2相对表达量降低组;组2为OprD2相对表达量正常组;组1与组2相比,对IPM、BPM、MEM、PEM的MIC值≥16μg/ml的菌株比例差异均有统计学意义(P＜0.01).组1中,28株同时对4种药物的MIC均≥16 μg/ml,其中有25株的OprD2的相对表达量明显减低(＜0.4);外膜孔蛋白OprD2转录水平与4种碳青霉烯类药物MICs之间呈负相关趋势.组2中,有16株9prD2基因发生突变,按照突变的类型主要分成4组;与PAO1相比,这些菌株对IPM、BPM、MEM、PEM的MIC值有不同程度的增加.结论 OprD2外膜蛋白的表达量减少或缺失是铜绿假单胞菌对亚胺培南耐药的主要机制,可能也与其他3种碳青霉烯类药物耐药有密切关系;铜绿假单胞菌的oprD2基因发生突变,可能会降低铜绿假单胞菌对这儿种碳青霉烯类药物的敏感性.     

Prevalence of faecal carriage of Carbapenemase Producing Enterobacteriaceae in healthy Indian subjects from the community

PurposeFaecal carriage of carbapenemase-producing Enterobacterales (CPE) has been extensively investigated in hospitalized patients, but limited data is available on the carriage rate in healthy individuals in India.MethodsA total of 1000 stool samples were screened for CPE from healthy individuals in Chennai (n ?= ?50), Hyderabad (n ?= ?184) and Mumbai (n ?= ?766). Diluted stool samples were cultured on chromID CARBA SMART plates. Growing colonies were screened for CPE by RAPIDEC® CARBA NP Test and minimum inhibitory concentration (MIC) of imipenem by E-Test. PCR was performed for confirmation of CPE genes.ResultsOut of the 1000 stool samples tested, 6.1% were positive for CPE. A total of 64 carbapenem resistant isolates (56 ?E.coli, 4 Klebsiella pneumoniae, 3 Enterobacter cloacae and 1 Citrobacter freundii) were recovered from ChromID CARBA SMART biplate. Carbapenemase production was identified in 57/64 isolates by RAPIDEC® CARBA NP test. PCR analysis showed 28 bla_NDM-1 and 33 bla_OXA48. Three remaining isolates (2 ?E.coli, 1 ?K.pneumoniae) were negative for the tested carbapenemase genes. Interestingly, out of these 61 PCR positive isolates, 49.1% displayed imipenem MIC within the susceptibility range on the basis of CLSI interpretative criteria.ConclusionsFaecal carriage of CPE among healthy individuals was 6.1%. Comprehensive measures to improve the sanitation scenario and implementation of National AMR action plan are needed to prevent further generation and dissemination of carbapenem resistant Enterobacterales (CRE).     

老年人亚胺培南耐药铜绿假单胞菌耐药性研究

目的 明确我院老年病人临床分离铜绿假单胞菌的耐药性、同源性及耐碳青霉烯菌株的基因型。方法 收集我院2006年5月-2009年5月自临床老年病人分离的262株铜绿假单胞菌,纸片扩散法测定其对16种抗菌药物的耐药性;琼脂稀释法和E test法测定耐碳青霉烯菌株对14种抗菌药物的MIC值,PCR扩增及克隆测序分析金属酶基因型。脉冲场凝胶电泳(PFGE)分析携带金属酶基因型菌株的同源性。结果 262株铜绿假单胞菌中筛选到104株耐碳青霉烯。104株耐碳青霉烯铜绿假单胞菌对氨苄西林/舒巴坦、头孢哌酮/舒巴坦两个含舒巴坦制剂药物耐药率分别为78.9％和35.9％,对多黏菌素E耐药率最低为6.0％,对米诺环素耐药率58.3％,其余抗菌药物耐药率均大于70.0％;104株亚胺培南耐药铜绿假单胞菌中12株携带金属酶基因,10株检测到有携带VIM-2基因的1类整合子。PFGE分型中12株菌株属于5个克隆株。结论 在我院流行的亚胺培南耐药铜绿假单胞菌中,金属酶基因不是最主要的基因型,金属β-内酰胺酶均为VIM-2型金属酶,耐药基因盒分布于不同的1类整合子中,整合子播散是最主要的流行方式。     

Optimal use of antibiotic resistance surveillance systems

Increasing concern about the emergence of resistance in clinically important pathogens has led to the establishment of a number of surveillance programmes to monitor the true extent of resistance at the local, regional and national levels. Although some programmes have been operating for several years, their true usefulness is only now being realised. This review describes some of the major surveillance initiatives and the way in which the data have been used in a number of different settings. In the hospital, surveillance data have been used to monitor local antibiograms and determine infection control strategies and antibiotic usage policies. In the community, surveillance data have been used to monitor public health threats, such as infectious disease outbreaks involving resistant pathogens and the effects of bioterrorism countermeasures, by following the effects of prophylactic use of different antibiotics on resistance. Initially, the pharmaceutical industry sponsored surveillance programmes to monitor the susceptibility of clinical isolates to marketed products. However, in the era of burgeoning resistance, many developers of antimicrobial agents find surveillance data useful for defining new drug discovery and development strategies, in that they assist with the identification of new medical needs, allow modelling of future resistance trends, and identify high-profile isolates for screening the activity of new agents. Many companies now conduct pre-launch surveillance of new products to benchmark activity so that changes in resistance can be monitored following clinical use. Surveillance data also represent an integral component of regulatory submissions for new agents and, together with clinical trial data, are used to determine breakpoints. It is clear that antibiotic resistance surveillance systems will continue to provide valuable data to health care providers, university researchers, pharmaceutical companies, and government and regulatory agencies.     

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control

Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries—chiefly Greece and Israel—have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.