·高被引論文摘要·

中國鮑曼不動(dòng)桿菌感染診治與防控專家共識(shí)

陳佰義，何禮賢，胡必杰，等

·高被引論文摘要·

被引頻次：294

中國鮑曼不動(dòng)桿菌感染診治與防控專家共識(shí)

陳佰義，何禮賢，胡必杰，等

鮑曼不動(dòng)桿菌已成為 21世紀(jì)臨床重要致病茵。鮑曼不動(dòng)桿菌基因組研究發(fā)現(xiàn)其具有快速獲得和傳播耐藥性的能力，多重耐藥、廣泛耐藥、全耐藥鮑曼不動(dòng)桿菌已呈世界性流行，成為全球抗感染領(lǐng)域的挑戰(zhàn)，更是目前我國最重要的“超級(jí)細(xì)菌”。由于鮑曼不動(dòng)桿菌在自然環(huán)境、醫(yī)院環(huán)境的廣泛存在及在住院患者的多部位定植，臨床醫(yī)生在鮑曼不動(dòng)桿菌感染的診斷、治療和預(yù)防控制上存在諸多困惑。為提高鮑曼不動(dòng)桿菌感染診治與防控水平，遏制我國鮑曼不動(dòng)桿菌耐藥性和感染流行的快速增長(zhǎng)，由《中華醫(yī)學(xué)雜志》組織，32位國內(nèi)知名專家共同發(fā)起，邀請(qǐng)全國326位專家參與，歷時(shí)7個(gè)多月，召開了 12場(chǎng)專題討論會(huì)，得到了衛(wèi)生部行業(yè)基金（《臨床多重耐藥菌醫(yī)院感染防控研究及應(yīng)用》，編號(hào)201002021）的支持，經(jīng)過充分的意見搜集和討論，最終達(dá)成了這份《中國鮑曼不動(dòng)桿菌感染診治與防控專家共識(shí)》。共識(shí)薈萃了國外鮑曼不動(dòng)桿菌感染診治與防控的最新進(jìn)展，總結(jié)了我國絕大多數(shù)權(quán)威專家對(duì)于鮑曼不動(dòng)桿菌感染診治與防控的寶貴經(jīng)驗(yàn)，是規(guī)范鮑曼不動(dòng)桿菌感染診治和防控的指導(dǎo)性文件。該共識(shí)的制定和提出，將對(duì)我國多重耐藥菌的診治與防控做出引領(lǐng)和示范，有助于改善我國鮑曼不動(dòng)桿菌感染診治與防控現(xiàn)狀，有助于保障醫(yī)療質(zhì)量和醫(yī)療安全，保障廣大患者的生命安全和健康權(quán)益。原中華醫(yī)學(xué)會(huì)會(huì)長(zhǎng)著名呼吸病專家鐘南山院士專門寄語：“合理用藥，預(yù)防不動(dòng)桿菌耐藥”。由于鮑曼不動(dòng)桿菌的自身特點(diǎn)，鮑曼不動(dòng)桿菌感染診治和防控仍有許多問題沒有解決，需要廣大專家的積極探索，積累經(jīng)驗(yàn)和循證醫(yī)學(xué)證據(jù)，不斷完善專家共識(shí)。

來源出版物：中國醫(yī)藥科學(xué), 2012, 2(8): 3-8

被引頻次：97

葡萄球菌屬連續(xù)分離株毒力與耐藥基因研究

糜祖煌，金輝，秦玲

摘要：目的：了解金黃色葡萄球菌（SAU）和凝固酶陰性葡萄球菌（CNS）連續(xù)分離株的 pvl毒力基因與β-內(nèi)酰胺類、氨基糖苷類、紅霉素類、四環(huán)素類、消毒劑耐藥基因狀況。方法：收集了100株SAU和27株CNS連續(xù)分離株，進(jìn)行pvl、mecA、aac（6′）/aph（2″）、aph（3′）-Ⅲ、ant（4′,4″）、ermA/B/C、msrA、tetM、qacA/B基因檢測(cè)。結(jié)果：SAUmecA基因陽性69株（69.0%）和CNSmecA基因陽性16株（59.3%），SAUmecA基因陽性株（MRSA）pvl、aac（6′）/aph（2″）、aph（3′）-Ⅲ、ant（4′,4″）、ermA/B/C、tetM、qacA/B基因檢出率高于mecA基因陰性株（MSSA）。結(jié)論：SAUmecA基因陽性株（MRSA）氨基糖苷類、四環(huán)素類、大環(huán)內(nèi)酯類耐藥相關(guān)基因檢測(cè)結(jié)果均支持MRSA具耐多藥特征；本組SAUmecA基因陽性的69株中8株攜帶pvl基因，即同時(shí)攜帶pvl毒力基因與β-內(nèi)酰胺類、氨基糖苷類、紅霉素類、四環(huán)素類、消毒劑耐藥基因，此類“超級(jí)細(xì)菌”應(yīng)為臨床防控重點(diǎn)。

葡萄球菌屬；毒力基因；耐藥基因

來源出版物：中華醫(yī)院感染學(xué)雜志, 2008, 18(4): 454-456

被引頻次：48

細(xì)菌抗生素耐藥性：耐藥機(jī)制與控制策略

李顯志，張麗

摘要：細(xì)菌對(duì)抗生素的耐藥性尤其是多重藥物耐藥性已成為全球關(guān)注的醫(yī)學(xué)與社會(huì)問題，嚴(yán)重地威脅著感染性疾病的治療，如常見于ESKAPE病原菌（源于腸球菌、金黃色葡萄球菌、肺炎克雷伯菌、鮑曼不動(dòng)桿菌、銅綠假單胞菌和腸道桿菌屬6種細(xì)菌的英文縮寫）的高度多重抗生素耐藥性。這些細(xì)菌包括“超級(jí)細(xì)菌”，因其本身基因結(jié)構(gòu)的多樣性和可移動(dòng)性使其進(jìn)化產(chǎn)生了多種耐藥機(jī)制以對(duì)抗抗生素的作用。耐藥細(xì)菌呈現(xiàn)的對(duì)多類不同化學(xué)結(jié)構(gòu)抗生素的高度耐藥性，使抗感染治療的藥物選擇極其困難。耐藥性基因可由細(xì)菌染色體或質(zhì)粒攜帶，并編碼介導(dǎo)產(chǎn)生抗生素滅活酶（如最近廣為報(bào)道的屬于金屬β-內(nèi)酰胺酶的 NDM-1碳青霉烯酶）、改變或保護(hù)抗生素作用靶位、降低抗生素進(jìn)入細(xì)菌胞內(nèi)和增強(qiáng)抗生素主動(dòng)外排泵系統(tǒng)活性將藥物排至胞外。目前研發(fā)用于臨床的新型抗生素極為有限，促使重新研究?jī)?yōu)化現(xiàn)有抗生素。人類迫切需要同時(shí)采取多種有效措施控制抗生素耐藥性，合理控制各類抗生素使用，以最大限度減少抗生素耐藥性發(fā)生與傳播，進(jìn)而延長(zhǎng)抗生素的有效時(shí)間，仍然是人類所面臨的長(zhǎng)期挑戰(zhàn)。

關(guān)鍵詞：抗生素耐藥性；多重耐藥性；耐藥機(jī)制；ESKAPE病原菌；超級(jí)細(xì)菌；感染治療

來源出版物：瀘州醫(yī)學(xué)院學(xué)報(bào), 2011, 34(5): 445-455

被引頻次：37

細(xì)菌耐藥現(xiàn)狀及治療——從超級(jí)細(xì)菌談起

趙敏

摘要：全球細(xì)菌耐藥形勢(shì)十分嚴(yán)峻，多耐藥、泛耐藥革蘭陰性菌逐年增加，成為抗感染治療中的難點(diǎn)。2010年在全球多個(gè)地區(qū)出現(xiàn)的產(chǎn)新德里金屬β-內(nèi)酰胺酶Ⅰ型（NDM-1）革蘭陰性細(xì)菌又一次敲響了警鐘。NDM-1是新發(fā)現(xiàn)的碳青霉烯酶，多見于大腸埃希菌和肺炎克雷伯菌，導(dǎo)致廣泛耐藥。臨床研究中多黏菌素、替甲環(huán)素及磷霉素治療多耐藥、泛耐藥腸桿菌感染有效。減少多耐藥、泛耐藥細(xì)菌的發(fā)生和傳播重在預(yù)防。

關(guān)鍵詞：耐藥；細(xì)菌；新德里金屬β-內(nèi)酰胺酶-1；變異

來源出版物：解放軍醫(yī)學(xué)雜志, 2011, 36(2): 533-538

被引頻次：32

細(xì)菌耐藥性產(chǎn)生的原因、機(jī)制及防治措施

趙明秋，沈海燕，潘文，等

摘要：20世紀(jì)40年代青霉素的問世將人類帶入了抗生素時(shí)代，抗感染治療由此進(jìn)入了新紀(jì)元，感染性疾病的病死率大大降低。半個(gè)世紀(jì)以來，人類一直把抗菌藥物作為抗感染治療最有力的武器。然而隨著抗菌藥物的廣泛應(yīng)用，感染性疾病的治療又遇到了新的挑戰(zhàn)——細(xì)菌對(duì)抗生素產(chǎn)生了耐藥性，而此種耐藥性表現(xiàn)為抗菌藥物使用得越多耐藥性亦變得越嚴(yán)重。目前已發(fā)現(xiàn)某些細(xì)菌對(duì)現(xiàn)有的幾乎全部抗菌藥物產(chǎn)生耐藥，超級(jí)細(xì)菌的出現(xiàn)使人類有可能再次回到面臨感染而無藥可醫(yī)的困境，控制細(xì)菌耐藥性的增長(zhǎng)已成為醫(yī)學(xué)界乃至全人類的當(dāng)務(wù)之急。正在逐漸建立自己的細(xì)菌耐藥監(jiān)測(cè)網(wǎng)絡(luò)，監(jiān)測(cè)細(xì)菌耐藥的流行狀況和規(guī)律，研究細(xì)菌產(chǎn)生耐藥性的機(jī)制。

關(guān)鍵詞：細(xì)菌；耐藥性；防治

來源出版物：中國畜牧獸醫(yī), 2011, 38(5): 38-50

被引頻次：26

關(guān)于超級(jí)細(xì)菌NDM-1的若干思考

黃留玉

摘要：自印度出現(xiàn)耐藥性“超級(jí)細(xì)菌”以來，英國、美國、加拿大、澳大利亞、荷蘭等國也相繼出現(xiàn)了“超級(jí)細(xì)菌”感染，使之成為繼“非典”“甲流”之后又一引起國際社會(huì)廣泛關(guān)注的全球公共衛(wèi)生問題。我國寧夏和福建也同時(shí)發(fā)現(xiàn)了“超級(jí)細(xì)菌”感染病例，再次引發(fā)了對(duì)濫用抗生素問題的思考。什么是超級(jí)細(xì)菌，為何會(huì)引起廣泛關(guān)注，我們?cè)撊绾螒?yīng)對(duì)？本刊特邀軍事醫(yī)學(xué)科學(xué)院疾病預(yù)防控制所專家撰寫此文，以饗讀者，為正確解讀“超級(jí)細(xì)菌”提供參考。

關(guān)鍵詞：抗藥性；細(xì)菌；新德里金屬β-內(nèi)酰胺酶-1；變異

來源出版物：解放軍醫(yī)學(xué)雜志, 2011, 38(5): 177-181

被引頻次：25

耐甲氧西林金黃色葡萄球菌的研究進(jìn)展

于旭紅，王冬，王睿

摘要：耐甲氧西林金黃色葡萄球菌（MRSA）已成為醫(yī)院感染重要的致病菌，MRSA引起的感染，因其耐藥高、死亡率高及經(jīng)濟(jì)負(fù)擔(dān)重，成為威脅全球公共衛(wèi)生安全的嚴(yán)重問題。MRSA多重耐藥現(xiàn)象日益嚴(yán)重。了解MRSA的現(xiàn)狀，才能更好地及時(shí)治療并且盡可能避免MRSA感染，因此本文對(duì)MRSA的流行現(xiàn)狀、臨床感染、治療藥物、預(yù)防傳播及經(jīng)濟(jì)負(fù)擔(dān)等最新研究現(xiàn)狀進(jìn)行概述。

關(guān)鍵詞：耐甲氧西林金黃色葡萄球菌；流行病學(xué)；感染

來源出版物：中國臨床藥理學(xué)雜志, 2011, 27(4): 306-310

被引頻次：23

超級(jí)細(xì)菌的警示與濫用抗生素潛在公共衛(wèi)生問題

程錦泉，劉少礎(chǔ)

摘要：新德里金屬-β-內(nèi)酰胺酶1（New Delhi metalloβ-lactamase 1，NDM-1）是2010年發(fā)現(xiàn)的一種超強(qiáng)耐藥性基因，這種基因一旦進(jìn)入細(xì)菌體內(nèi)將使細(xì)菌變得超級(jí)頑強(qiáng)，因此被稱為超級(jí)細(xì)菌。攜帶這一基因的細(xì)菌幾乎能抵御除替加環(huán)素和粘桿菌素以外的所有抗生素，甚至對(duì)碳青霉烯類抗生素也有耐藥性。諸多研究表明，細(xì)菌耐藥性的出現(xiàn)與變化，與抗生素的大量使用以至于濫用有關(guān)。超級(jí)細(xì)菌的出現(xiàn)，提醒人們抗生素濫用已成為全球性的公共衛(wèi)生問題，如不加以控制，其產(chǎn)生的后果將是人類所無法承受的。本文結(jié)合NDM-1的出現(xiàn)及其傳播特點(diǎn)，對(duì)抗生素使用中引發(fā)的細(xì)菌耐藥問題以及應(yīng)采取的相應(yīng)監(jiān)管措施進(jìn)行分析探討。

關(guān)鍵詞：抗生素濫用；超級(jí)細(xì)菌；細(xì)菌耐藥

來源出版物：中國公共衛(wèi)生, 2010, 26(12): 1521-1522

被引頻次：21

萬古霉素對(duì)金黃色葡萄球菌體外抗菌活性研究

余方友，李美蘭，林曉梅，等

摘要：目的：調(diào)查萬古霉素對(duì)金黃色葡萄球菌的體外抗菌活性。方法：收集溫州醫(yī)學(xué)院附屬第一醫(yī)院2005年2—7月從臨床各種標(biāo)本分離的金黃色葡萄球菌112株，PCR檢測(cè)mecA基因確定MRSA，采用瓊脂稀釋法和全自動(dòng)微生物分析儀檢測(cè)金黃色葡萄球菌萬古霉素 MIC值，使用4 mg/L萬古霉素腦心浸液瓊脂（BHIA）篩選異質(zhì)性耐萬古霉素金黃色葡萄球菌（hVRSA）。結(jié)果：MRSA的檢出率為64.3%，萬古霉素的 MIC大多數(shù)≤2 mg/L，MIC90為2 mg/L，有2株菌在4 mg/L萬古霉素BHIA平皿上生長(zhǎng)，經(jīng)菌群分析法證實(shí)非hVRSA。儀器法檢測(cè)的萬古霉素 MIC值與瓊脂稀釋法的符合率只有35.7%，瓊脂稀釋法萬古霉素MIC高于儀器法，儀器法檢測(cè)的2株萬古霉素中介耐藥的菌株經(jīng)瓊脂稀釋法和K-B法證實(shí)為敏感株。有6株對(duì)萬古霉素的 MIC為4 mg/L，按美國NCCLS/CLSI 2006年的標(biāo)準(zhǔn)被確定為萬古霉素中介耐藥株。結(jié)論：萬古霉素對(duì)金黃色葡萄球菌具有較強(qiáng)的體外抗菌活性，未發(fā)現(xiàn)耐藥株，但MIC值較大。儀器法檢測(cè)金黃色葡萄球菌對(duì)萬古霉素的敏感性結(jié)果不可靠。按NCCLS/CLSI 2006年的標(biāo)準(zhǔn)臨床上能檢測(cè)到對(duì)萬古霉素中介耐藥的金黃色葡萄球菌臨床分離株。

關(guān)鍵詞：金黃色葡萄球菌；萬古霉素；瓊脂稀釋法；全自動(dòng)微生物分析儀；耐藥性

來源出版物：中國微生態(tài)學(xué)雜志, 2006, 18(3): 240-242

被引頻次：18

人類與病原菌的軍備競(jìng)賽：NDM-1耐藥基因與超級(jí)細(xì)菌

孫明偉，鄭焙文，高福，等

摘要：在人類歷史上，每一次諸如鼠疫和肺結(jié)核病等瘟疫的大流行，都曾給人類的生存帶來巨大的威脅?？股氐膽?yīng)用使人類掌握了抵抗細(xì)菌感染的銳利“武器”，但同時(shí)病原菌也通過突變和水平基因轉(zhuǎn)移等方式產(chǎn)生了諸多耐藥基因，從而獲得了應(yīng)對(duì)抗生素殺傷的堅(jiān)固“盾牌”；于是人類又不斷地開發(fā)新式抗生素“武器”來破解病原菌的耐藥“盾牌”——場(chǎng)“軍備競(jìng)賽”愈演愈烈。近來研究發(fā)現(xiàn)，攜帶編碼NDM-1基因的耐藥質(zhì)粒不僅可以在細(xì)菌間轉(zhuǎn)移，而且能使所在宿主菌成為可以耐受幾乎全部抗生素的超級(jí)細(xì)菌。但是，憑借著日益進(jìn)步的科技和醫(yī)學(xué)，以及科學(xué)的用藥策略，我們一定可以再次戰(zhàn)勝超級(jí)細(xì)菌。

關(guān)鍵詞：NDM-1；超級(jí)細(xì)菌；軍備競(jìng)賽；耐藥基因

來源出版物：生物工程學(xué)報(bào), 2010, 26(11): 1461-1472

被引頻次：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.

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

被引頻次：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.

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

被引頻次：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.

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

被引頻次：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.

來源出版物：New England Journal of Medicine, 2002, 347(6): 385-394被引頻次：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

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

被引頻次：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.

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

被引頻次：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

來源出版物：AIDS, 2000, 14(4): 357-366

被引頻次：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.

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

被引頻次：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

來源出版物：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.

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

被引頻次：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