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“超级细菌”令世界紧张 新药研发赶不上变异
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| 2010年08月22日 07:41:01 来源： 新华国际 |
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比非典、甲流还可怕？十年内无药可治？容易扩散全球？最近，被部分媒体描述得可怕又致命的“超级细菌”成为热议话题。
在印度等南亚国家出现的耐药性“超级细菌”（NDM-1），已经蔓延到英国、美国、加拿大、澳大利亚和荷兰等国家。目前全球已有170人被感染，其中在英国至少造成5人死亡。在媒体和民众表达恐惧之时，也有人警惕地嗅到了“过度渲染”和“被利益集团操纵”的味道。
专家表示对“超级细菌”无需过度恐慌。然而，随着耐药性细菌队伍的不断壮大，却又给人们敲响滥用抗生素的警钟。细菌耐药性已成为21世纪全球关注的热点，它对人类生命健康所构成的威胁绝不亚于艾滋病、癌症和心血管疾病。有人担心如果出现一种超“超级细菌”，所有的抗生素都对它不起作用时，怎么办？
“超级细菌”令世界紧张
本报讯 8月13日，比利时医疗人员证实，一名比利时人死于据信源自南亚的“超级细菌”。医生曾用强力抗生素多黏菌素治疗这名患者，但仍无法挽救他的生命。
就在此前两天，英国医学杂志《柳叶刀传染病》刊登研究报告称，英国医院发现一类新的耐药细菌，这种细菌抗药性极强，已感染英国、美国、瑞典、荷兰、澳大利亚个别居民，报告将这类细菌携带的抗药基因命名为“新德里金属蛋白酶—1”（NDM-1）。据证实，比利时男子正是死于这种细菌。
新药研制需10年
有专家估计这种超级细菌可能发展成为全球卫生问题。研究人员说：“空中旅行和移居使这种超级细菌在不同国家之间迅速传播。”
英国卡迪夫大学11日发布公报指出，NDM—1基因最早由该校教授蒂姆·沃尔什于2009年发现，来源是一名曾到印度就医的瑞典人所携带的细菌。近两年来，英国医院先后发现有37宗“超级细菌”感染症，其中17名感染病人在印度、巴基斯坦和孟加拉等国家接受过整形或器官移植等外科手术。
NDM—1是一种超级抗药性基因。含这种基因的细菌对几乎所有抗生素具有免疫力。NDM－1基因可以在细菌间转移，导致更多“超级细菌”出现。美国疾病预防和控制中心流行病学家亚历山大·凯伦说，“超级细菌”之所以令人担忧，就在于这种“传染性”。
欧洲临床微生物和感染疾病学会说，预计至少10年内没有抗生素可以“消灭”含NDM—1基因的细菌。
无需过度恐慌
NDM-1基因之所以引起医学界的担忧，是因为携有该基因的一些细菌对抗生素具有抗药性。但法国发现携有这一基因的细菌对几种药物不具备有效“抵抗力”，医学专家因此呼吁民众不要惊慌。
另外，无论撰写超级细菌的报告作者还是中外权威专家都承认，所谓“超级细菌”远没有甲型流感那么强的传播能力，公众对此不必恐慌。研究人员发现，目前有两种抗生素对绝大部分“超级细菌”有效，一种是多黏菌素，另一种是替加环素。
现状
制药公司是幕后推手？
本报讯 “超级细菌”的危害是否被夸大？很快有人提出了这样的质疑。质疑者怀疑渲染“超级细菌”背后可能存在利益动机。
印度卫生部说，得出超级细菌源自印度的研究报告由两家生产抗生素的制药公司赞助，而“超级细菌”事件爆发后，多个制药企业在欧洲乃至全球股市上股价走高，生物医药板块飘红。
药物公司资助研究
印度卫生部的声明称，这项得出超级细菌源自印度的研究报告，是由欧盟、生物医学研究慈善机构威康信托和制药公司惠氏赞助的。据称，惠氏正是对超级病菌有效的抗生素替加环素的生产商。有报道称，研究报告的主笔人曾得到惠氏的旅费赞助，而报告的出台或许会大幅助长惠氏替加环素在全球范围内的销售。
而惠氏公司网站上发表公告称，他们一直为医学方面的独立研究做资助，但从未对其产生任何影响以妨碍其结果的客观公正性。
这究竟是不是制药公司的阴谋尚未可知，但事实却是，全球股市多家生物制药企业的股价在这一事件广受关注之后纷纷走高，生物医药板块整体飘红。
事实上，在历次全球性流行病的暴发中，制药公司从来都是受益者。例如，在去年甲流流行之际，各国医疗机构都纷纷提高警惕，大量采购了疫苗，这其中最大的受益者无疑是制药公司。
印度医疗旅游受挫
最夸张的情况发生在法国，为保证法国6500万人每人可接种一剂至两剂甲型流感疫苗，法国政府花费了8.69亿欧元(约合12.5亿美元)从疫苗生产商赛诺菲巴斯德公司购得9400万剂甲型流感疫苗。但是最终只有约600万法国人接种了疫苗，随着甲流疫情的逐渐消退，法国不得不着手为剩余的疫苗寻找出路。同样的情况也发生在荷兰、意大利、西班牙和德国等国。
然而，“超级细菌”事件却直接损害了印度蓬勃发展的医疗旅游。由于印度的医疗成本只有西方国家平均水平的五分之一，印度已经成为全球第二大医疗旅游目的地国，而本次事件无疑将使印度医疗旅游吸引力大打折扣。
质疑
对抗“超级细菌”
世卫四大对策
本报讯 名为NDM-1的超级细菌最初是在2009年被英国卡迪夫大学的蒂姆·沃尔什确认。他在一名瑞典病人身上发现了两种细菌，从中找到了NDM-1。这名患者曾在印度住院治疗。
NDM-1属于“肠桿菌”的一种。大肠桿菌、沙门氏菌、艰难梭菌，都是这个家族的成员。研究人员称，这种超级细菌的特性是能够附存于其他细菌生存，使其他细菌也产生其特别强的抗药能力。更令医学专家们担忧的是，NDM-1的抗药能力还会人传人，使抗生素对人无效，继而影响其他疾病的治疗。
NDM-1甚至对碳青霉烯类抗生素也具有耐药性，碳青霉烯类抗生素通常被认为是紧急治疗抗药性病徵的最后方法。最关键的是，NDM-1是以DNA的结构出现，被称为质体。研究人员称，它可以在细菌中自由复制和移动，从而使这种细菌拥有传播和变异的惊人潜能。
世界卫生组织20日敦促各国采取措施抗击耐药性细菌，减少细菌对抗生素产生抗药性的机会。
世卫组织建议各国政府将控制和预防耐药性细菌的重点集中在四个主要方面：
监测耐药性细菌；
合理使用抗生素，包括建议医务工作者和公众合理使用抗生素；
引进或执行有关停止无处方销售抗生素的法规；
严格执行预防和控制措施，比如洗手措施等，特别是在医疗保健机构中，这些措施必须得到执行。
世卫组织表示将继续帮助各国制定合理政策并协调国际努力，共同抗击耐药性细菌。世卫组织还表示，将把抗击耐药性细菌作为2011年世界卫生日主题。
困境
耐药性细菌队伍壮大
本报讯 世界上能称得上“超级细菌”之称的细菌有好几种，如耐甲氧西林金黄色葡萄球菌(MRSA)、耐甲氧西林表皮葡萄球菌(MRSE)和泛耐药性鲍曼不动杆菌等。它们是对三类或三类以上抗生素同时耐药的“多重耐药菌”，有些甚至对七种抗生素同时耐药的“泛耐药菌”。不过，“超级细菌”耐药性之强、演变之快以及队伍之壮大远超出人们的预料。
耐药性不断变强
以MRSA的耐药性变化为例：20世纪50年代以前，青霉素是治疗MRSA感染性疾病的有效药物，而到20世纪50年代开始出现对青霉素耐药的MRSA，但更为广谱的抗生素甲氧西林对其仍有效。但仅仅20年后，就出现了对甲氧西林耐药的MRSA。
MRSA自1961年被发现后，到上世纪80年代后期就已成为全球发生率最高的医院内感染病原菌之一。全世界范围内，目前能够被证实对MRSA有效的只有万古霉素。因此，MRSA被列为世界三大最难解决感染性疾患的第一位。MRSA被发现后以惊人的速度在世界范围内蔓延，据估计每年大约有十万人因为感染MRSA而住院治疗。
而更恐怖的是，1997年，对万古霉素中度耐药的金黄色葡萄球菌（VISA）出现了，而对万古霉素完全耐药的金黄色葡萄球菌（VRSA）也在五年后出现。广东省疾控中心微生物检测所副所长邓小玲博士指出，目前，国内不少医院在长期住院的重症病人身上发现了VISA的身影，而VRSA尚未在我国被发现，“但就目前耐药情况而言，治疗起来已非常棘手。”
最让人担心的事情是细菌的广泛蔓延。1997年，在纽约发现了CA-MRSA的另一个变种，而类似的变种出现了17个。它们的出现意味着MRSA家族开始走出医院，大开杀戒。监狱、体育馆等地方成为CA-MRSA感染的新根据地，病菌迅速在英、美两国蔓延，并有向世界性流行发展的趋势。
最怕“后抗生素时代”
浙江大学医学院第一附属医院传染病诊治国家重点实验室教授肖永红认为，这次出现的“超级细菌”本身并不可怕，但从长远看来，真正具有威胁性的，是不断产生新的“超级细菌”，它们会对越来越多的抗生素产生抗药性。
由此人们不禁担心，如果有一天，出现一种超“超级细菌”，所有的抗生素都对它不起作用时，怎么办？
“那人类就相当于重新回到了没有抗生素的年代，也就是所谓的"后抗生素时代"。”肖永红说。“后抗生素时代”描绘的是一幅可怕的景象：全球将面临抗生素类药品无效，人类将再次经历无法控制感染类疾病的黑暗时代。
不管以上假设是否将成为现实，可以肯定的是，人们无法预料下一个“超级细菌”的出现，而细菌耐药性已成为21世纪全球关注的热点，“它对人类生命健康所构成的威胁绝不亚于艾滋病、癌症和心血管疾病。”邓小玲说。
反思
滥用抗生素练出细菌抗药性
本报讯 19日，世界卫生组织新闻发言人陈蔚云在接受媒体采访时称，抗生素的滥用是“超级细菌”产生的罪魁祸首。她指出，“多重耐药菌的产生并非前所未有，也不是意料之外”，“逃过药物存活下来，也是细菌自身的生存机制”。
“超级细菌”的出现再次引起了人们对于滥用抗生素问题的思考。自上世纪40年代以青霉素为代表的第一批抗生素诞生以来，抗生素滥用已经成为一个全球性问题。超量、超时、不对症使用或未严格规范使用抗生素都属于滥用。
新药研发赶不上变异
如果从弗莱明1929年发表《论青霉菌培养物的抗菌作用》论文算起，抗生素与病菌之间的“拉锯战”已有80年。人类为了对付层出不穷的致病微生物，不断研发出各类新型抗生素。而细菌为了生存，不断变异进化，形成可耐受抗生素的新细菌，由此形成恶性循环。
2000年辉瑞的利奈唑烷的上市引起医学界的轰动，被人们寄予厚望。但仅仅不到一年，就出现了耐药病菌的报道。新药越来越少，耐药性的超级病菌却越来越多，造成这种局面的原因是新抗生素的开发速度远远跟不上耐药超级病菌发生的步伐。一种需要十几年研发的新型抗生素问世后，最快仅需几个月时间，就会有耐药细菌产生。这让人类遭遇了研发速度远远落后于耐药病菌出现速度的尴尬。
因此，有专家表示，单靠开发新的抗菌药对抗细菌并不现实，最根本的办法还是要合理使用抗生素。
完善抗生素监管制度
世卫组织早在今年5月就曾对合理用药发出警告指出，全球有50％以上的药物售卖和使用是错误甚至非法的，而利益驱动是全球抗生素用药量大增的主要因素。
印度传染病专家加法尔承认，印度是世界上滥用抗生素现象较为严重的国家，造成某些抗生素对60％至70％的印度人口不能起到有效抗菌作用。而发达国家这样的比例平均只有15％。
（来源：广州日报 专题文字/蒋林）
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Super bacteria" that the world can not keep up tension variation of drug development
August 22, 2010 07:41:01 Source: Xinhua International
Than SARS, a stream also horrible? Within a decade no cure? Easy to spread the world? Recently, was part of the media described as frightening and deadly "superbugs" have become hot topics.
In India and other South Asian countries, drug resistance emerged "super bacteria" (NDM-1), has spread to the United Kingdom, the United States, Canada, Australia and the Netherlands and other countries. Currently there are 170 people have been infected, of which at least five people in Britain died. Expression of fear in the media and the public when the smell was also alert to the "over-exaggerated" and "manipulated by interest groups" flavor.
Experts said the "super bacteria" do not panic. However, with the drug resistance of bacteria growing team, but the abuse of antibiotics to people sounded the alarm. Bacterial resistance has become the focus of attention of the 21st century, its human life and health threats posed by no less AIDS, cancer and cardiovascular disease. Some people worry that if there is a super "super bacteria", all the antibiotics it does not work, how do?
"Super bacteria" makes the world nervous
BEIJING August 13, Belgian medical staff confirmed that a letter from the Belgians die in South Asia, according to a "super bacteria." Doctors have used powerful antibiotic polymyxin treatment of the patient, but still save his life.
Just two days earlier, the British medical journal "The Lancet Infectious Diseases", published studies have reported that the British discovered a new class of hospital resistant bacteria, the bacteria resistant to strong, has infected the United Kingdom, United States, Sweden, the Netherlands, Australian residents in the report of such bacterial resistance gene carried by the name "New Delhi metalloproteinase -1" (NDM-1). It is confirmed that the Belgian man died from this bacteria is.
Drug research and take 10 years
Experts have estimated that this super-bacteria may develop into global health issues. The researchers said: "Air travel and migration make this super-bacteria spread rapidly between different countries."
Cardiff University on the 11th issued the communique said, NDM-1 gene was first proposed by Professor 蒂姆沃尔什 school in 2009 found that the source has been to India for medical treatment, a Swede by the carrying bacteria. The last two years, the United Kingdom found that 37 hospitals have a "super bacteria" infection, in which 17 infected patients in India, Pakistan and Bangladesh and other countries have received plastic surgery or organ transplantation surgery.
NDM-1 is a super-resistance gene. Bacteria containing this gene immune to almost all antibiotics. NDM-1 gene can be transferred between bacteria, leading to more "super bacteria" appear. U.S. Centre for Disease Control and Prevention epidemiologist, said Karen Alexander, "super bacteria" is cause for concern, is that this "contagious."
European Society of Clinical Microbiology and infectious diseases, said at least 10 years of antibiotics is expected to be "eliminated" with NDM-1 gene in bacteria.
No need to panic over
NDM-1 gene was aroused by the medical profession's concern is that some carrying the gene of bacteria resistant to antibiotics. But France was found carrying the genes of bacteria on several drugs do not have the effective "resistance", medical experts have urged people not to panic.
In addition, both written reports of super-bacteria, or foreign authority of experts believe that the so-called "super bacteria" is far from the spread of influenza so strong capacity, the public have no need to panic. The researchers found there are two kinds of antibiotics, the majority of "super bacteria" effective one is polymyxin, another is a ring for additional factors.
Status quo
Pharmaceutical companies are Behind the scenes?
PRC "super bacteria" whether the danger was exaggerated? Soon it was suggested that such a question. Skeptics doubt rendered "super bacteria" behind the motives of interest may exist.
India's Health Ministry said the super bacteria obtained from a study in India by two pharmaceutical companies to sponsor the production of antibiotics, and "super bacteria" incident, a number of pharmaceutical companies on the stock market in the European and global stock prices, bio- Chinese plate gains across the board.
Drug companies fund research
India's Health Ministry said in a statement, the super-bacteria obtained from the Indian study, by the European Union, the bio-medical research charity Wellcome Trust and the pharmaceutical company Wyeth-sponsored. Alleged that Wyeth is an effective antibiotic against super bacteria plus cyclophilin for manufacturers. It is reported that the study's lead author who has been the travel sponsorship of Wyeth, and the report may substantially contribute to the introduction of additional ring for prime Wyeth worldwide sales.
The Wyeth Web site issued a statement saying they have been for the medicine to do independent research funding, but never have any impact on its results in order to hinder the objective impartiality.
Is this not a conspiracy of pharmaceutical companies remains to be seen, but the fact is that many bio-pharmaceutical companies worldwide stock market shares in this wide attention after the incident have higher overall gains across the board biomedical plate.
In fact, in previous outbreaks of the global epidemic, the pharmaceutical companies has always been the beneficiaries. For example, a stream in the last year, the occasion of popular, national health agencies have alert, bulk purchase of vaccines, it is undoubtedly the biggest beneficiaries of the pharmaceutical companies.
Indian medical tourism setback
The most exaggerated the situation in France, 6500 to ensure the French people will each be inoculated 1-2 influenza vaccine, the French government spent 869 million euros (about 1.25 billion U.S. dollars) from the vaccine manufacturers Sainuofeiba de company bought 94 million influenza vaccine. But in the end only about 6 million French people vaccinated, with a current outbreak is waning, the French have started to find way out for the remainder of the vaccine. The same situation also occurred in the Netherlands, Italy, Spain and Germany and other countries.
However, the "super bacteria" has directly harmed the event that India's booming medical tourism. As medical costs in India is only the western one-fifth the national average, India has become the world's second largest medical tourism destination, but this incident will undoubtedly less attractive medical tourism in India.
Question
Against the "super bacteria"
Four measures of WHO
PRC named NDM-1 super bacteria was first in 2009 by Cardiff University's 蒂姆沃尔什 confirmed. He was found in a Swedish patients, two bacteria, to find the NDM-1. This patient has been hospitalized in India.
NDM-1 belongs to "Enterobacteriaceae" one. E. coli, Salmonella, Clostridium difficile, is a member of the family. The researchers said that the characteristics of super-bacteria that can live attached to exist in other bacteria, so that other bacteria also produce resistance to its particularly strong. What is more worrying is that medical experts, NDM-1 resistance to human transmission will make antibiotics ineffective against people, thereby affecting the treatment of other diseases.
NDM-1 and even carbapenems are resistant, carbapenem is generally considered an emergency treatment of drug-resistant symptoms of last resort. The key is, NDM-1 is based on the structure of DNA appeared, known as plasmids. The researchers said the bacteria it can freely copy and move, so that the bacteria have spread and mutation of the amazing potential.
World Health Organization, 20, urges States to take measures to combat drug-resistant bacteria, antibiotic resistant bacteria to reduce the chance.
WHO recommends governments to control and prevention of bacterial drug resistance focused on four main areas:
Monitoring bacterial drug resistance;
Rational use of antibiotics, including the proposed medical workers and the public rational use of antibiotics;
Introduction or implementation of the cessation of non-prescription sales of antibiotics and regulations;
Strict implementation of preventive and control measures, such as hand-washing measures, especially in the health care sector, these measures must be implemented.
WHO said it would continue to help countries to develop sound policies and to coordinate international efforts to jointly combat drug-resistant bacteria. WHO also said it would fight against resistant bacteria as the theme of World Health Day 2011.
Dilemma
Growth of resistant bacteria in the ranks
PRC in the world can be called "super germs," said the bacteria there are several, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and the Pan-drug resistance Bowman Acinetobacter so. They are a three or three or more antibiotics, while resistance to the "multi-drug resistant", and some of the seven kinds of antibiotics, while resistance to the "pan-resistant." However, the "super bacteria" strength of drug resistance, evolution, and the ranks of fast growing far exceeded expectations.
Resistance running strong
MRSA resistance to change: the 20th century 50 years ago, penicillin is the treatment of MRSA infections and effective drugs, and 50 years of the 20th century began to penicillin resistant MRSA, but more broad-spectrum antibiotic trimethoprim Xilin its still valid. But only after 20 years, the emergence of methicillin resistant MRSA.
Since MRSA was discovered in 1961, to the late 80s of last century had become the world's highest incidence of infectious pathogens in hospitals. Worldwide, the current can be proven effective against MRSA, only vancomycin. Thus, MRSA was listed as the top three most difficult to solve the first infectious disease. MRSA was discovered at an alarming rate worldwide spread, it is estimated that about 100 000 people each year because of MRSA infection while hospitalized.
More terror was, in 1997, with moderate resistance to vancomycin of Staphylococcus aureus (VISA) appears, and completely resistant to vancomycin of Staphylococcus aureus (VRSA) also occurs after five years . Guangdong Province, deputy director of CDC microbial detection Dr. Deng Xiaoling pointed out that, quite a few hospitals in the long-stay critically ill patients found a VISA figure, but not VRSA was found in China, "but on the current drug situation made, treatment has been very difficult up. "
The most worrying thing is the wide spread of bacteria. In 1997, in New York discovered another variant of CA-MRSA, while the emergence of similar variants of 17. The emergence of MRSA means that they start out of the hospital family, slaughter. Prisons, stadiums and other places to become the new CA-MRSA infection base, the virus rapidly in Britain and the United States spread, and a trend to the global epidemic.
Fear "post-antibiotic era"
First Affiliated Hospital of Zhejiang University State Key Laboratory diagnosis of infectious diseases, Professor XIAO that the emergence of "super bacteria" itself is not terrible, but in the long run, truly threatening, is constantly creating new " Super bacteria ", they will more and more antibiotics.
Thus people can not help but worry that if one day, the emergence of a super "super bacteria", all the antibiotics it does not work, how do?
"That's the equivalent of the human back is not the era of antibiotics, the so-called" post-antibiotic era "." XIAO said. "Post-antibiotic era" paint a terrible picture: the world will face ineffective antibiotic drugs, human beings can not control infection will again experience the dark ages of diseases.
Regardless of whether these assumptions become a reality, certainly yes, people can not anticipate the next one "super bacteria" appear, and bacterial resistance Xing the 21 century hot spot of global concern that it "Human Health and the threat posed by Jue Bu Asia in AIDS, cancer and cardiovascular disease. "Deng Xiaoling said.
Reflection
Abuse of the bacteria resistant to antibiotics training
PRC 19, the World Health Organization spokesman Chen Wei Yun, said in an interview, the overuse of antibiotics is the "super bacteria" produce the culprit. She pointed out that "multi-drug resistant which is not unprecedented, nor is it unexpected," "escape the drugs to survive, but also their survival mechanism of bacteria."
"Super bacteria" was again raises the issue of abuse of antibiotics. 40 years since the last century to penicillin antibiotics, represented by the birth of the first since the abuse of antibiotics has become a global problem. Excessive overtime, do not use or strictly regulate the use of expectant antibiotics misuse.
Variation of new drug development can not keep up
If released from Fleming in 1929, "culture of Penicillium Antibacterial effect of" counting paper, between antibiotics and bacteria, "tug of war" has been 80 years. To deal with emerging human pathogenic microorganisms, we can develop all kinds of new antibiotics. The bacteria in order to survive, and constantly evolving variations, to form a new bacterial antibiotic resistance, thus a vicious circle.
2000, Pfizer's linezolid listing sensation caused the medical profession, had been high hopes. But only less than a year, resistant bacteria appeared in the report. Fewer and fewer new drugs, resistant superbugs are more and more, the reason for this situation is the development of new antibiotic resistant super-speed lags far behind the pace of pathogens. Development of a need than a decade after the advent of new antibiotics, the fastest time of only a few months, there will be resistance in bacteria. This allows much faster development of the human face behind the resistance of bacteria occurring at a rate of embarrassment.
Therefore, some experts said that the development of new antibiotics alone against the bacteria is not realistic and the most fundamental way to the rational use of antibiotics.
Improve the regulatory regime of antibiotics
WHO early this year, once on the rational use of medicines in May issued a warning that more than 50% of the global drug sale and use of wrong or even illegal, and the benefits driving the sharp rise in global antibiotic drugs a major factor.
Jaafar recognized infectious disease experts in India, India is the world's more serious abuse of antibiotics in the state, leading to some antibiotics from 60 to 70 percent of India's population can not play an effective antibacterial action. The ratio of the average in developed countries such only 15%.
(Source: Guangzhou Daily feature writing / Jiang Lin)
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