·高被引论文摘要·

中国鲍曼不动杆菌感染诊治与防控专家共识

陈佰义，何礼贤，胡必杰，等

·高被引论文摘要·

被引频次：294

中国鲍曼不动杆菌感染诊治与防控专家共识

陈佰义，何礼贤，胡必杰，等

鲍曼不动杆菌已成为 21世纪临床重要致病茵。鲍曼不动杆菌基因组研究发现其具有快速获得和传播耐药性的能力，多重耐药、广泛耐药、全耐药鲍曼不动杆菌已呈世界性流行，成为全球抗感染领域的挑战，更是目前我国最重要的“超级细菌”。由于鲍曼不动杆菌在自然环境、医院环境的广泛存在及在住院患者的多部位定植，临床医生在鲍曼不动杆菌感染的诊断、治疗和预防控制上存在诸多困惑。为提高鲍曼不动杆菌感染诊治与防控水平，遏制我国鲍曼不动杆菌耐药性和感染流行的快速增长，由《中华医学杂志》组织，32位国内知名专家共同发起，邀请全国326位专家参与，历时7个多月，召开了 12场专题讨论会，得到了卫生部行业基金（《临床多重耐药菌医院感染防控研究及应用》，编号201002021）的支持，经过充分的意见搜集和讨论，最终达成了这份《中国鲍曼不动杆菌感染诊治与防控专家共识》。共识荟萃了国外鲍曼不动杆菌感染诊治与防控的最新进展，总结了我国绝大多数权威专家对于鲍曼不动杆菌感染诊治与防控的宝贵经验，是规范鲍曼不动杆菌感染诊治和防控的指导性文件。该共识的制定和提出，将对我国多重耐药菌的诊治与防控做出引领和示范，有助于改善我国鲍曼不动杆菌感染诊治与防控现状，有助于保障医疗质量和医疗安全，保障广大患者的生命安全和健康权益。原中华医学会会长著名呼吸病专家钟南山院士专门寄语：“合理用药，预防不动杆菌耐药”。由于鲍曼不动杆菌的自身特点，鲍曼不动杆菌感染诊治和防控仍有许多问题没有解决，需要广大专家的积极探索，积累经验和循证医学证据，不断完善专家共识。

来源出版物：中国医药科学, 2012, 2(8): 3-8

被引频次：97

葡萄球菌属连续分离株毒力与耐药基因研究

糜祖煌，金辉，秦玲

摘要：目的：了解金黄色葡萄球菌（SAU）和凝固酶阴性葡萄球菌（CNS）连续分离株的 pvl毒力基因与β-内酰胺类、氨基糖苷类、红霉素类、四环素类、消毒剂耐药基因状况。方法：收集了100株SAU和27株CNS连续分离株，进行pvl、mecA、aac（6′）/aph（2″）、aph（3′）-Ⅲ、ant（4′,4″）、ermA/B/C、msrA、tetM、qacA/B基因检测。结果：SAUmecA基因阳性69株（69.0%）和CNSmecA基因阳性16株（59.3%），SAUmecA基因阳性株（MRSA）pvl、aac（6′）/aph（2″）、aph（3′）-Ⅲ、ant（4′,4″）、ermA/B/C、tetM、qacA/B基因检出率高于mecA基因阴性株（MSSA）。结论：SAUmecA基因阳性株（MRSA）氨基糖苷类、四环素类、大环内酯类耐药相关基因检测结果均支持MRSA具耐多药特征；本组SAUmecA基因阳性的69株中8株携带pvl基因，即同时携带pvl毒力基因与β-内酰胺类、氨基糖苷类、红霉素类、四环素类、消毒剂耐药基因，此类“超级细菌”应为临床防控重点。

葡萄球菌属；毒力基因；耐药基因

来源出版物：中华医院感染学杂志, 2008, 18(4): 454-456

被引频次：48

细菌抗生素耐药性：耐药机制与控制策略

李显志，张丽

摘要：细菌对抗生素的耐药性尤其是多重药物耐药性已成为全球关注的医学与社会问题，严重地威胁着感染性疾病的治疗，如常见于ESKAPE病原菌（源于肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠道杆菌属6种细菌的英文缩写）的高度多重抗生素耐药性。这些细菌包括“超级细菌”，因其本身基因结构的多样性和可移动性使其进化产生了多种耐药机制以对抗抗生素的作用。耐药细菌呈现的对多类不同化学结构抗生素的高度耐药性，使抗感染治疗的药物选择极其困难。耐药性基因可由细菌染色体或质粒携带，并编码介导产生抗生素灭活酶（如最近广为报道的属于金属β-内酰胺酶的 NDM-1碳青霉烯酶）、改变或保护抗生素作用靶位、降低抗生素进入细菌胞内和增强抗生素主动外排泵系统活性将药物排至胞外。目前研发用于临床的新型抗生素极为有限，促使重新研究优化现有抗生素。人类迫切需要同时采取多种有效措施控制抗生素耐药性，合理控制各类抗生素使用，以最大限度减少抗生素耐药性发生与传播，进而延长抗生素的有效时间，仍然是人类所面临的长期挑战。

关键词：抗生素耐药性；多重耐药性；耐药机制；ESKAPE病原菌；超级细菌；感染治疗

来源出版物：泸州医学院学报, 2011, 34(5): 445-455

被引频次：37

细菌耐药现状及治疗——从超级细菌谈起

赵敏

摘要：全球细菌耐药形势十分严峻，多耐药、泛耐药革兰阴性菌逐年增加，成为抗感染治疗中的难点。2010年在全球多个地区出现的产新德里金属β-内酰胺酶Ⅰ型（NDM-1）革兰阴性细菌又一次敲响了警钟。NDM-1是新发现的碳青霉烯酶，多见于大肠埃希菌和肺炎克雷伯菌，导致广泛耐药。临床研究中多黏菌素、替甲环素及磷霉素治疗多耐药、泛耐药肠杆菌感染有效。减少多耐药、泛耐药细菌的发生和传播重在预防。

关键词：耐药；细菌；新德里金属β-内酰胺酶-1；变异

来源出版物：解放军医学杂志, 2011, 36(2): 533-538

被引频次：32

细菌耐药性产生的原因、机制及防治措施

赵明秋，沈海燕，潘文，等

摘要：20世纪40年代青霉素的问世将人类带入了抗生素时代，抗感染治疗由此进入了新纪元，感染性疾病的病死率大大降低。半个世纪以来，人类一直把抗菌药物作为抗感染治疗最有力的武器。然而随着抗菌药物的广泛应用，感染性疾病的治疗又遇到了新的挑战——细菌对抗生素产生了耐药性，而此种耐药性表现为抗菌药物使用得越多耐药性亦变得越严重。目前已发现某些细菌对现有的几乎全部抗菌药物产生耐药，超级细菌的出现使人类有可能再次回到面临感染而无药可医的困境，控制细菌耐药性的增长已成为医学界乃至全人类的当务之急。正在逐渐建立自己的细菌耐药监测网络，监测细菌耐药的流行状况和规律，研究细菌产生耐药性的机制。

关键词：细菌；耐药性；防治

来源出版物：中国畜牧兽医, 2011, 38(5): 38-50

被引频次：26

关于超级细菌NDM-1的若干思考

黄留玉

摘要：自印度出现耐药性“超级细菌”以来，英国、美国、加拿大、澳大利亚、荷兰等国也相继出现了“超级细菌”感染，使之成为继“非典”“甲流”之后又一引起国际社会广泛关注的全球公共卫生问题。我国宁夏和福建也同时发现了“超级细菌”感染病例，再次引发了对滥用抗生素问题的思考。什么是超级细菌，为何会引起广泛关注，我们该如何应对？本刊特邀军事医学科学院疾病预防控制所专家撰写此文，以飨读者，为正确解读“超级细菌”提供参考。

关键词：抗药性；细菌；新德里金属β-内酰胺酶-1；变异

来源出版物：解放军医学杂志, 2011, 38(5): 177-181

被引频次：25

耐甲氧西林金黄色葡萄球菌的研究进展

于旭红，王冬，王睿

摘要：耐甲氧西林金黄色葡萄球菌（MRSA）已成为医院感染重要的致病菌，MRSA引起的感染，因其耐药高、死亡率高及经济负担重，成为威胁全球公共卫生安全的严重问题。MRSA多重耐药现象日益严重。了解MRSA的现状，才能更好地及时治疗并且尽可能避免MRSA感染，因此本文对MRSA的流行现状、临床感染、治疗药物、预防传播及经济负担等最新研究现状进行概述。

关键词：耐甲氧西林金黄色葡萄球菌；流行病学；感染

来源出版物：中国临床药理学杂志, 2011, 27(4): 306-310

被引频次：23

超级细菌的警示与滥用抗生素潜在公共卫生问题

程锦泉，刘少础

摘要：新德里金属-β-内酰胺酶1（New Delhi metalloβ-lactamase 1，NDM-1）是2010年发现的一种超强耐药性基因，这种基因一旦进入细菌体内将使细菌变得超级顽强，因此被称为超级细菌。携带这一基因的细菌几乎能抵御除替加环素和粘杆菌素以外的所有抗生素，甚至对碳青霉烯类抗生素也有耐药性。诸多研究表明，细菌耐药性的出现与变化，与抗生素的大量使用以至于滥用有关。超级细菌的出现，提醒人们抗生素滥用已成为全球性的公共卫生问题，如不加以控制，其产生的后果将是人类所无法承受的。本文结合NDM-1的出现及其传播特点，对抗生素使用中引发的细菌耐药问题以及应采取的相应监管措施进行分析探讨。

关键词：抗生素滥用；超级细菌；细菌耐药

来源出版物：中国公共卫生, 2010, 26(12): 1521-1522

被引频次：21

万古霉素对金黄色葡萄球菌体外抗菌活性研究

余方友，李美兰，林晓梅，等

摘要：目的：调查万古霉素对金黄色葡萄球菌的体外抗菌活性。方法：收集温州医学院附属第一医院2005年2—7月从临床各种标本分离的金黄色葡萄球菌112株，PCR检测mecA基因确定MRSA，采用琼脂稀释法和全自动微生物分析仪检测金黄色葡萄球菌万古霉素 MIC值，使用4 mg/L万古霉素脑心浸液琼脂（BHIA）筛选异质性耐万古霉素金黄色葡萄球菌（hVRSA）。结果：MRSA的检出率为64.3%，万古霉素的 MIC大多数≤2 mg/L，MIC90为2 mg/L，有2株菌在4 mg/L万古霉素BHIA平皿上生长，经菌群分析法证实非hVRSA。仪器法检测的万古霉素 MIC值与琼脂稀释法的符合率只有35.7%，琼脂稀释法万古霉素MIC高于仪器法，仪器法检测的2株万古霉素中介耐药的菌株经琼脂稀释法和K-B法证实为敏感株。有6株对万古霉素的 MIC为4 mg/L，按美国NCCLS/CLSI 2006年的标准被确定为万古霉素中介耐药株。结论：万古霉素对金黄色葡萄球菌具有较强的体外抗菌活性，未发现耐药株，但MIC值较大。仪器法检测金黄色葡萄球菌对万古霉素的敏感性结果不可靠。按NCCLS/CLSI 2006年的标准临床上能检测到对万古霉素中介耐药的金黄色葡萄球菌临床分离株。

关键词：金黄色葡萄球菌；万古霉素；琼脂稀释法；全自动微生物分析仪；耐药性

来源出版物：中国微生态学杂志, 2006, 18(3): 240-242

被引频次：18

人类与病原菌的军备竞赛：NDM-1耐药基因与超级细菌

孙明伟，郑焙文，高福，等

摘要：在人类历史上，每一次诸如鼠疫和肺结核病等瘟疫的大流行，都曾给人类的生存带来巨大的威胁。抗生素的应用使人类掌握了抵抗细菌感染的锐利“武器”，但同时病原菌也通过突变和水平基因转移等方式产生了诸多耐药基因，从而获得了应对抗生素杀伤的坚固“盾牌”；于是人类又不断地开发新式抗生素“武器”来破解病原菌的耐药“盾牌”——场“军备竞赛”愈演愈烈。近来研究发现，携带编码NDM-1基因的耐药质粒不仅可以在细菌间转移，而且能使所在宿主菌成为可以耐受几乎全部抗生素的超级细菌。但是，凭借着日益进步的科技和医学，以及科学的用药策略，我们一定可以再次战胜超级细菌。

关键词：NDM-1；超级细菌；军备竞赛；耐药基因

来源出版物：生物工程学报, 2010, 26(11): 1461-1472

被引频次：1331

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance

Magiorakos, AP; Srinivasan, A; Carey, RB; et al.

来源出版物：Clinical Microbiology and Infection, 2012, 18(3): 268-281

被引频次：1116

Structure of a covalently trapped catalytic complex of HIV-I reverse transcriptase: Implications for drug resistance

Huang, HF; Chopra, R; Verdine, GL; et al.

Abstract: A combinatorial disulfide cross-linking strategy was used to prepare a stalled complex of human immunodeficiency virus-type 1 (HIV-1) reverse transcriptase with a DNA template: primer and a deoxynucleoside triphosphate (dNTP), and the crystal structure of the complex was determined at a resolution of 3.2 angstroms. The presence of a dideoxynucleotide at the 3’-primer terminus allows capture of a state in which the substrates are poised for attack on the dNTP. Conformational changes that accompany formation of the catalytic complex produce distinct clusters of the residues that are altered in viruses resistant to nucleoside analog drugs. The positioning of these residues in the neighborhood of the dNTP helps to resolve some Long-standing puzzles about the molecular basis of resistance. The resistance mutations are Likely to influence binding or reactivity of the inhibitors, relative to normal dNTPs, and the clustering of the mutations correlates with the chemical structure of the drug.

来源出版物：Science, 1998, 282(5394): 1669-1675

被引频次：862

Epidemiology of drug-resistance: Implications for a post-antimicrobial era

Cohen, ML

Abstract: In the last several years, the frequency and spectrum of antimicrobial-resistant infections have increased in both the hospital and the community. Certain infections that are essentially untreatable have begun to occur as epidemics both in the developing world and in institutional settings in the United States. The increasing frequency of drug resistance has been attributed to combinations of microbial characteristics, selective pressures of antimicrobial use, and societal and technologic changes that enhance the transmission of drug-resistant organisms. Antimicrobial resistance is resulting in increased morbidity, mortality, and health-care costs. Prevention and control of these infections will require new antimicrobial agents, prudent use of existing agents, new vaccines, and enhanced public health efforts toreduce transmission.

来源出版物：Science, 1997, 257(5073): 1050-1055

被引频次：831

Antiretroviral-drug resistance among patients recently infected with HIV

Little, SJ; Holte, S; Routy, JP; et al.

Abstract:Among persons in North America who are newly infected With the human immunodeficiency virus (HIV), the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent. We performed a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV in plasma samples from 377 subjects with primary HIV infection who had not yet received treatment and who were identified between May 1995 and June 2000 in 10 North American cities. Responses to treatment could be evaluated in 202 subjects. Over the five-year period, the frequency of transmitted drug resistance increased significantly. The frequency of high-level resistance to one or more drugs (indicated by a value of more than 10 for the ratio of the 50 percent inhibitory concentration [IC50] for the subject’s virus to the IC50for a drug-sensitive reference virus) increased from 3.4 percent during the period from 1995 to 1998 to 12.4 percent during the period from 1999 to 2000 (P = 0.002), and the frequency of multidrug resistance increased from 1.1 percent to 6.2 percent (P = 0.01). The frequency of resistance mutations detected by sequence analysis increased from 8.0 percent to 22.7 percent (P < 0.001), and the frequency of multidrug resistance detected by sequence analysis increased from 3.8 percent to 10.2 percent (P = 0.05). Among subjects infected with drug-resistant virus, the time to viral suppression after the initiation of antiretroviral therapy was longer (P = 0.05), and the time to virologic failure was shorter (P = 0.05). The proportion of new HIV infections that involve drug-resistant virus is increasing in North America. Initial antiretroviral therapy is more likely to fail in patients who are infected with drug-resistant virus. Testing for resistance to drugs before therapy begins is now indicated even for recently infected patients.

来源出版物：New England Journal of Medicine, 2002, 347(6): 385-394被引频次：731

The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP

Yun, Cai-Hong; Mengwasser, Kristen E; Toms, Angela V; et al.

Abstract: Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M. Threonine 790 is the “gatekeeper”residue, an important determinant of inhibitor specificity in the ATP binding pocket. The T790M mutation has been thought to cause resistance by sterically blocking binding of TKIs such as gefitinib and erlotinib, but this explanation is difficult to reconcile with the fact that it remains sensitive to structurally similar irreversible inhibitors. Here, we show by using a direct binding assay that T790M mutants retain low-nanomolar affinity for gefitinib. Furthermore, we show that the T790M mutation activates WT EGFR and that introduction of the T790M mutation increases the ATP affinity of the oncogenic L858R mutant by more than an order of magnitude. The increased ATP affinity is the primary mechanism by which the T790M mutation confers drug resistance. Crystallographic analysis of the T790M mutant shows how it can adapt to accommodate tight binding of diverse inhibitors, including the irreversible inhibitor HKI-272, and also suggests a structural mechanism for catalytic activation. We conclude that the T790M mutation is a “generic” resistance mutation that will reduce the potency of any ATP-competitive kinase inhibitor and that irreversible inhibitors overcome this resistance simply through covalent binding, not as a result of an alternative binding mode.

Keywords: lung cancer; tyrosine kinase; x-ray crystallography

来源出版物：Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(6): 2070-2075

被引频次：697

Biofilm formation by the fungal pathogen Candida albicans: Development, architecture, and drug resistance

Chandra, J; Kuhn, DM; Mukherjee, PK; et al.

Abstract:Biofilmsarea protectedniche for micro-organisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like (ALS) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae, which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.

来源出版物：Journal of Bacteriology, 2001, 183(18): 5385-5394

被引频次：670

Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population

Bangsberg, DR; Hecht, FM; Charlebois, ED; et al.

Abstract:Objective: To examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. Design and setting: A cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. Participants: Thirty-four HIV-infected people with a median of 12 months of PI therapy. Main outcomes: Adherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. Results: Median adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirtyeight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36%-65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). Conclusion: A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

Keywords:access to therapy; adherence; HIV; highly active antiretroviral therapy; homeless; injection drug use; protease inhibitor; resistance; viral load

来源出版物：AIDS, 2000, 14(4): 357-366

被引频次：609

Global surveillance for antituberculosis-drug resistance, 1994-1997

Pablos-Mendez, A; Raviglione, MC; Laszlo, A; et al.

Abstract:Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organizationlnternational Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14344). Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5percent) was more common than resistance to rifampin (1.8 percent) or ethambutol (1.0 percent). The prevalence of primary multidrug resistance was 1.4 percent (range, 0 to 14.4 percent). Among patients with histories of treatment for one month or less, the prevalence of resistance to any of the four drugs was 36.0 percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6 percent for single-drug resistance (range, 2.3 to 42.4 percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent). Particularly high prevalences of multidrug resistance were found in the former Soviet Union, Asia, the Dominican Republic, and Argentina. Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.

来源出版物：New England Journal of Medicine, 1998, 338(23): 1641-1649

被引频次：515

Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance

Holden, MTG; Feil, EJ; Lindsay, JA; et al.

Abstract: Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximate to 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: A recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive communityacquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximate to 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC476), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA communityacquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.

Keywords: organochlorine compounds (OCs); mussels; Asia-Pacific region; developing countries; developed nations

来源出版物：Proceedings of the National Academy of Sciences of the United States of America, 2004 101(26): 9786-9791

Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance

Boehm, T; Folkman, J; Browder, T; et al.

Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogenous and have a low mutational rate. Therefore, anti-angiogenic therapy directed against a tumour’s endothelial cells should, in principle, induce little or no drug resistance, Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy, These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor, An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

来源出版物：Nature, 1997, 390(6658): 404-407

被引频次：1247

Abstract: Many different definitions for multidrugresistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided.

antimicrobial agents; definitions; extensively drug resistant; multidrug resistant; pandrug resistant