深圳南山医院2010年细菌耐药性监测

目的了解某院2010年临床住院患者送检标本分离菌株对常用抗菌药物的耐药性。方法采用全自动细菌鉴定仪及配套鉴定与药物敏感试验试剂,检测临床分离菌对常用抗菌药物的耐药性,并用WHONET5.4软件进行统计分析。结果2010年1-12月共分离病原菌2 192株,其中革兰阳性菌占32.03%,革兰阴性菌占67.97%。金黄色葡萄球菌和凝固酶阴性葡萄球菌中,甲氧西林耐药株(MRSA 和 MRCNS)分别占 19.69%和54.59%。葡萄球菌属中耐甲氧西林株对β 内酰胺类抗生素和其他测试抗菌药物的耐药率显著高于甲氧西林敏感株。 MRSA对复方磺胺甲口恶唑、利福平、四环素、庆大霉素的耐药率分别为1.67%、41.54%、44.62%、58.46%;MRCNS对利福平、四环素的耐药率分别为17.27%和36.70%;未发现万古霉素、替考拉宁和利奈唑胺耐药株。肠球菌属中,粪肠球菌对大多数测试抗菌药物的耐药率低于屎肠球菌;此次监测首次在该院发现1株耐利奈唑胺的粪肠球菌,未发现耐万古霉素菌株。大肠埃希菌、肺炎克雷伯菌中产超广谱β 内酰胺酶(ESBLs)株分别为 44.29%和 15.79%。肠杆菌科细菌中产ESBLs株对抗菌药物的耐药率均比非产ESBLs株高。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为 26.73%和13.79%,不动杆菌属(鲍曼不动杆菌占92.91%) 对二者的耐药率分别为31.35%和 27.17%。结论细菌耐药性仍呈增长趋势, 尤其革兰阴性杆菌;鲍曼不动杆菌及铜绿假单胞菌对碳青霉烯类抗生素耐药性的增加,对临床构成严重威胁。合理选用抗菌药物,及早检测泛耐药菌, 加强感染控制措施是当务之急。     

某地区分离自呼吸系统感染患者产ESBLs、AmpC酶肠杆菌科细菌耐药性检测

目的 分析肠杆菌科细菌临床分离株产超广谱β-内酰胺酶(ESBLs)和头孢菌素酶(AmpC酶)情况,及其与肠杆菌科细菌耐药性的关系.方法 收集该地区12家医院2009～2010年分离自呼吸系统感染患者呼吸道标本的肠杆菌科细菌1 612株,双纸片增效法检测ESBLs、三维试验检测AmpC酶、K-B纸片法检测菌株耐药性,采用χ2检验进行统计学分析.结果 1 612株细菌中,产ESBLs和AmpC酶菌株检出率分别为45.0%(726/1 612)和11.6%(187/1 612),产酶株对多种抗菌药物的耐药率高于非产酶株;未检出碳青霉烯类抗菌药物耐药菌株.结论 分离自该地区呼吸道感染患者呼吸道标本的产ESBLs和AmpC酶肠杆菌科细菌具有多药耐药性,应加强细菌耐药性监测,采取有效措施防止耐药性的水平传播.     

产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的检测及耐药性

目的了解大肠埃希茵和肺炎克雷伯菌产超广谱β-内酰胺酶（ESBLs）的耐药性,为临床合理使用抗茵药物提供依据。方法细菌的鉴定及药敏采用Microscan WalkAway 40SI全自动系统。产ESBLs菌株药敏试验用琼脂纸片扩散法,根据2005年美国临床实验室标准化委员会（NCCLS）标准判断结果。结果检出产ESBLs细菌46株,检出率25．7％,其中产ESBLs大肠埃希菌33株,检出率26．7％,产ESBLs肺炎克雷伯菌13株,检出率32．5％;产ESBLs菌株对碳青霉烯类（亚胺培南）、头孢西丁及β-内酰胺酶抑制剂复合物、阿米卡星耐药性较低为0％～28．7％,对其余抗菌药物都产生较高的耐药性。结论重视产ESBLs细菌检测,根据药敏试验结果合理用药,碳青霉烯类、头孢西丁及β-内酰胺酶抑制剂复合物、阿米卡星是目前治疗产ESBLs细菌有效抗菌药物。     

Evaluation of a lateral flow immunoassay to detect CTX-M extended-spectrum β-lactamases (ESBL) directly from positive blood cultures for its potential use in Antimicrobial Stewardship programs

BackgroundBloodstream infections (BSI) caused by extended-spectrum beta-lactamases Enterobacteriaceae (ESBL-E) are associated with high rates of treatment failure and increased mortality, especially when appropriate antimicrobial therapy is delayed. Our aim was to evaluate the anticipation of ESBLs detection and the potential improvement of the time response of the Vitek 2 System (BioMérieux; France).MethodsWe compared this lateral flow immunoassay when used directly on fluid from positive blood cultures to the VITEK2 AST system. We evaluated 80 isolates, 61 tested directly on fluid from positive blood cultures and 19 tested on fluid from blood cultures spiked with known ESBL positive and negative organisms.ResultsThe concordance between the CTX-LFIA and the reference method (Vitek 2) had a Cohen´s Kappa coefficient of 0.97, indicating a particularly good correlation between both compared methods.ConclusionThis lateral flow immunoassay can be more rapid than the Vitek 2 for earlier presumptive identification of CTX- M ESBLs and can be useful to anticipate results and the adjustment of antimicrobial therapy.     

某院分离的大肠埃希菌和肺炎克雷伯菌ESBLs基因检测及分型

目的了解某院分离的大肠埃希菌和肺炎克雷伯菌产生的超广谱β 内酰胺酶（ESBLs）基因型。方法采用表型确证试验测定并收集该院产ESBLs大肠埃希菌（40株）和肺炎克雷伯菌（20株）,提取质粒DNA。采用特异性引物扩增TEM、SHV和 CTX M系列基因,测序后进行序列分析。结果60株表型确证试验阳性的大肠埃希菌和肺炎克雷伯菌,聚合酶链反应（PCR）扩增均阳性,包括TEM、SHV、CTX M 3组和CTX M 9组4种基因型。大肠埃希菌中上述4种基因型阳性率分别为37.50%（15株）、2.50%（1株）、62.50%（25株）、50.00%（20株）;肺炎克雷伯菌上述4种基因型阳性率分别为40.00%（8株）、90.00%（18株）、65.00%（13株）、40.00%（8株）。100.00%的大肠埃希菌和80.00%的肺炎克雷伯菌产生blaCTX M,12.50%(5/40)的大肠埃希菌和25.00%(5/20)的肺炎克雷伯菌携带2种CTX M酶基因。23例TEM基因皆为TEM 1型;19例SHV型基因包括SHV 1型6株、SHV 11型6株、SHV 12型5株及SHV 25型2株,仅SHV 12为ESBLs基因,且均来源于肺炎克雷伯菌;66例CTX M型基因,其中CTX M 14在大肠埃希菌和肺炎克雷伯菌的检出率分别为45.00%和35.00%,CTX M 55检出率均为35.00%,CTX M 15检出率分别为20.00%和15.00%,检出少量CTX M 3、CTX M 65、CTX M 101及CTX M 123基因型。结论该院分离的大肠埃希菌和肺炎克雷伯菌ESBLs基因型以CTX M 为主,其次为SHV 12。CTX M基因型中以CTX M 14最为常见,CTX M 101及CTX M 123型ESBLs为山东省首次检出。     

Recommendation for treatment of severe infections caused by Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs)

Extended-spectrum β-lactamase (ESBL)-producing organisms are a global problem. No randomized controlled trials have ever been performed to guide optimal treatment. However, in vitro studies and observational studies strongly suggest that carbapenems (imipenem or meropenem) should be regarded as drugs of choice for serious infections due to ESBL-producing organisms. Other β-lactam antibiotics (cefepime, β-lactam/β-lactamase inhibitor combinations) are not suitable as first-line therapy. The increasing frequency of the association between quinolone resistance and ESBL production have greatly limited the role of this class of antibiotic against ESBL producers.     

A hospital outbreak of extended-spectrum β-lactamase-producing Klebsiella pneumoniae investigated by RAPD typing and analysis of the genetics and mechanisms of resistance

Between July and September 1997 a ceftazidime- and aminoglycoside-resistant strain of Klebsiella pneumoniae infected or colonized seven patients on three paediatric wards at Guy's Hospital in London. The patients were mostly neonates or infants recovering from cardiac surgery for congenital defects. The organism was probably introduced by an asymptomatic patient from Greece and the subsequent outbreak could largely be explained by person-to-person spread on individual wards and frequent transfers of patients between wards. The outbreak was controlled by patient isolation and attention to handwashing, and there were no fatalities. The organisms were non-typeable by serology but had a characteristic RAPD profile. They produced the extended-spectrum β-lactamase SHV-5 and the aminoglycoside-modifying enzymes AAC(6′) + probably AAC(3)II, encoded on a conjugative plasmid of approximately 160 kb. Two other patients had multi-resistant klebsiellas, one of them an SHV-5 producer and one a TEM-5 producer, but these could be distinguished from each other and from the outbreak strain by serological and RAPD typing and by the genetics and mechanisms of their resistances. Three other multi-resistant enterobacteria were isolated during the outbreak: an Escherichia coli that had acquired the 160 kb resistance plasmid from the epidemic klebsiella, a Citrobacter isolated from one of the patients with the klebsiella but which did not produce SHV-5, and a TEM-5-producing Enterobacter. This outbreak illustrates the importance of screening patients from high-risk areas for multiply-resistant organisms on admission, and the value of bacterial typing and analysis of resistance mechanisms to define the epidemiology of hospital infection.     

The role of tazobactam-based combinations for the management of infections due to extended-spectrum β-lactamase-producing Enterobacterales: Insights from the Society of Infectious Diseases Pharmacists

Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a global threat to public health due to their antimicrobial resistance profile and, consequently, their limited available treatment options. Tazobactam is a sulfone β-lactamase inhibitor with in vitro inhibitory activity against common ESBLs in Enterobacterales, including CTX-M. However, the role of tazobactam-based combinations in treating infections caused by ESBL-producing Enterobacterales remains unclear. In the United States, two tazobactam-based combinations are available, piperacillin-tazobactam and ceftolozane-tazobactam. We evaluated and compared the roles of tazobactam-based combinations against ESBL-producing organisms with emphasis on pharmacokinetic/pharmacodynamic exposures in relation to MIC distributions and established breakpoints, clinical outcomes data specific to infection site, and considerations for downstream effects with these agents regarding antimicrobial resistance development. While limited data with ceftolozane-tazobactam are encouraging for its potential role in infections due to ESBL-producing Enterobacterales, further evidence is needed to determine its place in therapy. Conversely, currently available microbiologic, pharmacokinetic, pharmacodynamic, and clinical data do not suggest a role for piperacillin-tazobactam, and we caution clinicians against its usage for these infections.     

The search for new antimicrobials: why we need new options

The increasing identification of antibiotic-resistant pathogens that cause serious infections cannot be ignored. Although the future cannot be predicted with certainty, it is surely possible that an extensive epidemic of resistant bacterial infections could potentially harm millions of people. Given that it takes more than 10 years to establish the efficacy and safety of new compounds, there is an urgent need to restock the antibiotic pipeline. Only a few new antibacterial agents have received approval by the US Food and Drug Administration in the last 5 years, including linezolid in 2001, cefditoren, pivoxil and ertapenem in 2002, gemifloxacin and daptomycin in 2003, and telithromycin in 2004. Many of these agents are improved derivatives from established classes of antibiotics, and several are directed primarily at resistant Gram-positive bacteria (e.g., linezolid and daptomycin). One promising new addition is the recent approval of tigecycline (Tigacyl?, Wyeth) in June 2005.     

Extended-spectrum and CMY-type β-lactamase-producing Escherichia coli in clinical samples and retail meat from Pittsburgh, USA and Seville, Spain

Infections due to Escherichia coli producing extended-spectrum β-lactamase (ESBL) or CMY-type β-lactamase (CMY) are increasingly observed in non-hospitalized patients. The origin of these organisms is uncertain, but retail meat contaminated with E. coli may be a source. In the present study, clinical information and strains collected from patients infected or colonized with ESBL-producing and CMY-producing E. coli at hospitals in Pittsburgh, USA and Seville, Spain were investigated. Retail meat purchased in these cities was also studied for the presence of these organisms. Twenty-five and 79 clinical cases with ESBL-producing E. coli and 22 cases and one case with CMY-producing E. coli were identified in Pittsburgh and Seville, respectively. Among them all, community-acquired and healthcare-associated cases together constituted 60% of the cases in Pittsburgh and 73% in Seville. Community-acquired cases were more common in Seville than in Pittsburgh (49% vs. 13%; p   <0.001). ESBL-producing and CMY-producing E. coli isolates were commonly recovered from the local retail meat. In particular, 67% (8/12) of retail chickens in Seville and 85% (17/20) of those in Pittsburgh contained ESBL-producing and CMY-producing E. coli isolates, respectively. Among the ESBL-producing isolates, CTX-M and SHV were the most common ESBL types in both clinical and meat isolates. Approximately half of the ESBL-producing and CMY-producing E. coli isolates from meat belonged to phylogenetic groups associated with virulent extra-intestinal infections in humans. Community and healthcare environments are now significant reservoirs of ESBL-producing and CMY-producing E. coli . Retail meat is a potential source of these organisms.