人类抗菌 细菌抗药

刘君 转载自 新京报 | 2009-04-20 10:51 | 收藏 | 投票

 

  

人类抗菌细菌抗药
 
青霉素的发现打响了人类与病菌之间“持久战”的第一枪。
人类抗菌细菌抗药
 
病菌抗药性的产生,很大程度上与人类滥用抗生素有关。

 

  结核病曾经是人类的第一大杀手,但随着抗菌素的广泛应用,结核病的危害直线下降,在上世纪六七十年代人类颇有“大获全胜”的感觉。然而,在上世纪末,结核病却又卷土重来,疫情直线回升,大有重新找回“第一杀手”位置之势,而最令人担心的,莫过于耐药性结核病例的大量出现。

  1 耐药导致治疗困难

  上世纪90年代以来,全球结核病疫情明显回升,世界卫生组织认为,回升的主要原因包括:盲目乐观,放松了结核病控制工作;移民和难民增加,这些移民和难民大多数已经感染了结核菌,发病率很高,他们的发病加重了当地结核病的流行;HIV感染降低了人体对结核菌的免疫力。

  而最重要的,莫过于是多耐药结核病例增加,病人肺内的结核菌对多种抗结核药物发生耐药。

  结核病的耐药性分成单耐药、多耐药、耐多药、严重耐多药这几个层次。之所以耐药性分这样的层次,是因为治疗结核病的药物也是有层次的。医学界把治疗结核病的药物分为一线和二线两大类。

  中国疾控中心结核病防治临床中心办公室主任李亮表示,一线药物效果最好,而且价格便宜副作用小,治疗时会首先使用,如果无效,再使用二线药物。这就好比进攻敌人,开始进行精确空中打击,如果不能消灭敌人,只好投入地面部队。

  一线药物包括异烟肼和利福平等,对结核病有比较好的治疗作用。而二线药物包括氟喹诺酮类抗生素,比如氧氟沙星等。

  结核病耐药性层次的划分正是根据这些药的层次,单耐药就是结核杆菌对一种一线抗结核药物耐药;多耐药就是结核杆菌对一种以上的一线抗结核药物耐药;耐多药指结核杆菌至少对异烟肼、利福平耐药;严重耐多药指结核病患者感染的结核杆菌除至少对两种主要一线抗结核药物异烟肼、利福平耐药外,还对三种二线抗结核注射药物中的至少一种耐药。

  治疗耐药性结核杆菌要多花费大量金钱,一般结核病人的治疗费用,每人仅需要150-200元;而耐多药结核病人的治疗费用,每人需要1.5万至2万元。结核病人因不能支付医药费而中断治疗者,在临床上并不少见。而大量用药产生的副作用会对病人身体造成很大的损害,更重要的是,很可能无论怎么用药,都不能杀死病人体内的结核杆菌,最终导致病人死亡。

  2 道魔相争已有多时

  那么,结核杆菌为什么会产生抗药性呢?

  1928年,英国细菌学家弗莱明无意中发现培养皿中生长有青霉菌的区域细菌就无法生长,从而导致了青菌素的发现,也无意揭开了达尔文演化论在医学实践上大规模运用的序幕。

  科学家们认为,之所以大多数最有效的抗生素都来自霉菌,是因为抗生素实际上是亿万年多种霉菌与细菌斗争的过程中,产生出来的攻击细菌的“化学武器”。它本身就是演化的产物,特点是对细菌的杀伤力大,而对其他生命体的杀伤力很小。青霉素之所以能既杀死病菌,又不损害人体细胞,原因在于青霉素所含的青霉烷能使病菌细胞壁的合成发生障碍,导致病菌溶解死亡,而人和动物的细胞则没有细胞壁。然而,当抗生素被大规模运用到人体上时,却促进了细菌的演化。不适应抗生素的菌株被杀死了,但适应抗生素的菌株却大量繁殖。

  青霉素在上世纪40年代被大量应用之后,人类进入抗生素时代,传染病死亡率下降很快,以致1969年美国卫生总监觉得可以宣告,现在已经是“可以把关于传染病的书收起来的时候了”。然而,细菌的耐药性逐渐浮出水面。以最常见的感染病原菌葡萄球菌为例。1941年,看起来所有葡萄球菌都可以被青霉素杀死,但到1944年,已经有了能产生分解青霉素的酶的菌株出现。到上世纪90年代,95%的葡萄球菌都对青霉素有一定的抗药性。

  另外,人类还用其他药物,比如磺胺类药物杀灭细菌。和青霉素类似,很多细菌也对磺胺产生了耐药性。

  3 人为失误催生恶魔

  耐药结核杆菌又是怎么产生的呢?现在医学界普遍认为,耐药结核是人为失误制造出来的“恶魔”。李亮说,从原理上来讲,结核杆菌产生抗药性有两种途径,一种是自然突变,但如果同时使用两种以上的药,细菌通过自然突变产生对两种药耐药性的可能性不大。

  另一种是化学因素导致细菌突变。如果药品的质量有问题,或者患者的依从性不好,未按要求服药,那么患者体内的化学环境就有可能诱发结核杆菌突变,从而产生耐药结核杆菌。所以说,大多数耐药结核杆菌都是人为失误培养出来的。

  正确的用药方式是早用、有规律、全疗程适量用药,还要联合用药。之所以要联合用药,就是要把所有结核杆菌“一下子打死”,不让它们演化出耐药的品种。

  如果因为人为失误,在病人体内培育出了耐药菌群,那么治疗就会相当困难。使用二线药物疗程会相当长,这时病人漏用药的可能性更大,更加大了培养出耐药品种的可能性。现在这个问题因为艾滋病的流行而变得更加复杂。李亮说,艾滋病和耐药结核相互依存,起到狼狈为奸的作用,因为艾滋病人自身免疫系统不能杀死病菌,所以病菌更容易在多药的化学环境中从容地突变,很多耐药性的结核杆菌都是从艾滋病患者体内“培养”出来的。

  因为结核杆菌繁殖速度很慢,通常要一天左右才分裂出一代,所以从提取标本到确定其耐药性需要2-3个月的时间,让治疗工作相当被动。现在正在研究加快这个速度,最新成果已经把检测时间加快到2-3天。

  一旦病人体内被“培养”出耐药病菌,他就成为一个危险的传染源,把这些“无药可治”的病菌传播到空气中。

  4 过于恐慌也无必要

  李亮说,结核病已经成为对人类健康的最大威胁之一。其中的原因是首先结核病很难通过个人防护有效预防,其二是它的病菌可以在人体内潜伏很多年。

  最近有说法认为,卡介苗已经失效了,这种说法被和耐药性结核联系在一起。李亮说,这是两个问题。对于卡介苗的作用,现在有很大的争论,有人认为它可以提供80%的防护作用,有人认为它的作用是0,也就是一点用都没有。现在我国一般认为卡介苗还是有效的,它并不能避免结核病的感染和发病,但可以减少重症结核病的发生概率。我们最终的目标,是培养出一种结核病的高效疫苗,一种特别有效的药物,但现在这两点都没有做到。所以,对结核病的防治一定要引起足够重视。

  当然,人们也不必太惊慌。李亮说,结核病菌在空气中能存活3天左右,在太阳光下十几分钟就死了。它还是在飞沫中的传染性最大,如果落在地上或者水中传染性就小了。不用担心在生活中随时会接触到耐药结核杆菌。一般来说,如果不是被身体中已经产生耐药结核杆菌的患者直接传染,患上耐药性的结核病的可能性不大。如果保持空气流通,经常锻炼身体,注意预防感冒,多数人都可以远离结核病这个恶魔。

  新知专题采写/本报记者 刘铮本专题感谢:李亮(中国疾控中心结核病防治临床中心办公室主任)

Human antimicrobial resistant bacteria
04 years http://www.sina.com.cn 2009 on 19 day Beijing 00:17


 
 

The discovery of penicillin started between humans and bacteria, "protracted war" the first shot.
 
 

The emergence of drug-resistant bacteria, to a large extent related to the abuse of antibiotics and human.

TB was once the largest killer of mankind, but with the extensive use of antibiotics, tuberculosis fall hazards in the sixties and seventies of the last century quite human "victory" feeling. However, in the last century, but tuberculosis resurgence, pick-up in a straight line the epidemic, a great back, "the first killer" of potential locations, and most worrying, is the resistance of the large number of TB cases.

1 drug resistance led to the treatment of difficult

The last century since the 90's, the global TB epidemic rise significantly, the World Health Organization believes that the main reason for recovery include: blind optimism, relaxation of the tuberculosis control work; increase in immigrants and refugees, the majority of these immigrants and refugees have been infected with the TB incidence a high rate of incidence increased their local prevalence of TB; HIV infection reduces the body immunity against Mycobacterium tuberculosis.

And most important, is a multi-drug-resistant TB cases increased, the pulmonary tuberculosis patients a wide range of anti-tuberculosis drug resistance occurred.

TB drug resistance is divided into single-drug resistance, multidrug resistance, MDR, MDR-serious levels of these. The reason why such resistance at the level of treatment of tuberculosis because there are levels of the drug. Medical treatment of tuberculosis to first-and second-line drugs are divided into two broad categories.

Tuberculosis control in China CDC Director of the Office of Clinical Center, Liang said that the best first-line drugs, and cheap side effects, treatment will be the first to use, if invalid, then the use of second-line drugs. This is like attacking the enemy, precision air strikes to start, if not destroy the enemy, but to put ground forces.

First-line drugs, including isoniazid and rifampicin equality, there is relatively good for TB treatment. And second-line drugs including fluoroquinolone antibiotics, such as for example ofloxacin.

TB drug resistance is divided into levels according to the level of these drugs, single drug-resistant TB is on a first-line anti-tuberculosis drug resistance; multi-drug-resistant TB is more than one line of anti-tuberculosis drug resistance; MDR Mycobacterium tuberculosis drug refers to at least isoniazid, rifampicin resistance; serious means of multi-drug resistant Mycobacterium tuberculosis infection in patients with the exception of at least two main first-line anti-TB drugs isoniazid, rifampicin resistance, but also on the injection of three second-line anti-tuberculosis drug resistance in at least one.

Treatment of drug-resistant TB takes charge of a large amount of money, the general treatment of TB costs only 150-200 yuan per person; and MDR-TB treatment costs, per person needs 15000-20000 yuan. TB patients unable to pay medical expenses due to the interruption of treatment, are not uncommon in clinical practice. And a large number of side-effects of medication on the patient's body a great deal of harm and, more importantly, is likely to use no matter how, we can not kill the TB patients, and ultimately cause deaths.

Two have been competing for a long time magic

So, why have drug-resistant TB do?

In 1928, the United Kingdom Alexander Fleming accidentally discovered in a Petri dish growth area Penicillium bacteria can not grow, which led to the discovery of actinomycin Green and has no intention of opening a Darwinian evolution of medical practice in large-scale a prelude to use.

Scientists believe that the reason why the majority of the most effective antibiotics from Streptomyces, is because the antibiotics are actually a variety of fungi and bacteria millions of years the process of struggle, resulting in attacks by bacteria, "chemical weapons." It is itself a product of evolution, characterized by the destruction of bacteria, and other life on a small body of mass destruction. Penicillin is able to not only kill the bacteria without damaging human cells due to penicillin Penicillium contained n the synthesis of cell wall of bacteria can occur obstacles, resulting in the death of the bacteria dissolved, and human and animal cells, there is no cell wall. However, when large-scale use of antibiotics by humans, they promoted the evolution of bacteria. Strains of antibiotics were not suited to kill, but to adapt to antibiotics, but the large population of strains.

Penicillin in the last century was the 40's after a large number of applications, humanity has entered the era of antibiotics, infectious disease mortality has declined rapidly, so that the health director of the United States in 1969 that can be declared, and is now "able to close the book on infectious diseases with the time had. " However, the resistance of bacteria gradually surfaced. The most common pathogenic staphylococcus infection as an example. In 1941, looks all aureus can be killed by penicillin, but in 1944, has been decomposed to produce the enzyme penicillin strain emerged. To the last century 90's, 95% of Staphylococcus aureus have a certain degree of resistance to penicillin.

In addition, the human use of other drugs also, such as sulfa drugs to kill bacteria. And similar to penicillin, many bacteria also have had a sulfa drug resistance.

Human errors in the birth of the devil 3

How drug-resistant TB is selected? The medical profession is now generally agreed that drug-resistant TB is created by human error, "the devil." Liang said that the principle of speaking, the emergence of drug-resistant Mycobacterium tuberculosis in two ways, one is a natural mutation, but if at the same time the use of two or more drugs, bacteria through natural mutation of the two drugs have the possibility of drug resistance Great.

The other is the chemical factors of bacterial mutation. If the quality of drugs, or patients with poor compliance, did not require medication, so patients may be the chemical environment of Mycobacterium tuberculosis-induced mutations, resulting in drug-resistant Mycobacterium tuberculosis. Therefore, the majority of drug-resistant TB were trained by human error.

The correct use of medication is early, regular, full course of appropriate drugs, but also combined. The reason why combination therapy is to all of Mycobacterium tuberculosis, "all of a sudden death", not allowing them to evolve drug-resistant variety.

If it is due to human error, in the patient's body to produce a drug-resistant group, then the treatment will be rather difficult. Second-line drugs will be used for a long course of treatment, when patients are more likely to leak medication, a greater variety of training out the possibility of resistance. Now the problem because the prevalence of AIDS has become more complex. Liang said that the AIDS and drug-resistant TB are interdependent and play a role acted as their own immune system, AIDS virus can not be killed, so the bacteria more vulnerable to chemicals in the multi-drug environment easily mutation, a lot of resistance in Mycobacterium tuberculosis AIDS patients from "training" out.

TB breeding because of very slow, usually only a day or so to split the generation, so samples from the extract to determine its resistance need 2-3 months of time for treatment rather passive. Now being studied to speed up the pace, the latest achievement has been to speed up the detection time to 2-3 days.

Once the patient has been "training" a drug-resistant bacteria, he would become a dangerous source of infection, these "no-cure" the disease spread into the air.

4 is also no need to panic too much

Liang said that the TB to human health has become one of the greatest threats. The reason is first of all, TB is difficult to effectively prevent the adoption of personal protection, and the second is the bacteria it can be latent in the human body for many years.

The recent allegation that BCG has been a failure, and this was linked to drug-resistant tuberculosis. Liang said that this is two questions. The role of BCG, there are a lot of controversy, some people believe that it can provide 80% of the protective effect, it was felt that its role is to 0, that is, that are not used. BCG is now generally believed that China is still effective, it can not avoid the infection and incidence of tuberculosis, but can reduce the probability of the occurrence of severe tuberculosis. Our ultimate goal is to develop a highly effective TB vaccine, a particularly effective drug, but now these two have not been done. Therefore, prevention and treatment of TB must be caused by insufficient attention.

Of course, people do not have to panic too much. Liang said that the TB bacteria can survive in the air for about three days, in ten minutes under the sun on the dead. It is also in the infectious droplets in the biggest fall on the ground or if the water on the smaller infectious. Not have to worry about at any time in life will come into contact with drug-resistant Mycobacterium tuberculosis. In general, if not already produced by the body of patients with drug-resistant Mycobacterium tuberculosis direct infection, suffering from TB drug resistance is unlikely. If adequate ventilation, regular exercise, pay attention to the prevention of influenza, the majority of people can be far away from the demons of tuberculosis.

News topics written / our reporter Liu Zheng thanked the topic: Liang (China CDC tuberculosis control director of the Office of Clinical Center)

 

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[ 作者:佚名    转贴自:本站原创    点击数:198    更新时间:2009-4-19    文章录入:nnb ]

 

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协和专家门诊部艾滋病治疗中心主任、教授、专家,中医药疑难病专治网站长等。论文《艾滋病中医论治探析》登载《中国性病艾滋病》2003版杂志,发明的艾滋病治疗新药康生丹自2002年临床应用至今疗效显著,现有中国唯一艾滋病新药3代…
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