细菌的耐药性（图）

 

Antibiotic Resistance

胡德良 译

1.Resistant Bacteria

1. 耐药菌

Increased antibiotic use and misuse has generated an increasing number of resistant pathogenic strains, presenting a significant public health problem. Alexander Fleming was one of the first to voice concern about antibiotics and stress that misuse of the drugs could lead to resistance. In his 1945 Nobel Prize lecture, Fleming ended with a cautionary remark saying; “but I would like to sound one note of warning… it is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.” His warnings came at the same time as infections with antibiotic resistant bacteria strains were beginning to increase. One hospital reported that the percentage of penicillin-resistant Staphylococcus aureus infections had increased from 14% in 1946 to 59% by 1950.

抗生素应用和滥用的不断增加导致了耐药的病原菌株数量不断上升，引起了严重的公共健康问题。亚历山大·弗莱明是最早对抗生素问题表示关心的人之一，他强调了滥用抗生素会导致耐药性。1945年，弗莱明在接受诺贝尔奖时，他是以告诫的话语来结束演讲的：“但是，我要提出一条警告……在实验室里使细菌对青霉素耐药并不难，只要将它们暴露于药物浓度不足以杀死它们的环境即可，而同样的耐药情况偶尔也发生在人体中。”随着他的警告，耐药菌株感染的情况也开始增加了。根据一家医院的报告，耐青霉素金黄色葡萄球菌的感染率从1946年的14%上升到1950的59%。

 The ideal dosage and duration of antibiotic treatment will kill all susceptible bacteria and provide minimal opportunity for resistance to occur. When a bacterial infection is treated with antibiotics, any bacteria that have become resistant will survive, particularly if the treatment dose is too low or the duration too short. Antibiotics used for a variety of purposes outside of medicine have also contributed to the increase of resistant strains. The continual exposure of bacteria to low doses of antibiotics added to hand soaps, cleaning products, laundry detergent, and feed for livestock, selects for the survival of antibiotic-resistant bacteria.

 在抗生素治疗方面，理想的剂量和疗程将会杀死所有的敏感细菌，而产生耐药性的几率会最小。当利用抗生素治疗细菌感染的时候，特别是如果给药剂量太小或疗程太短的话，任何产生耐药性的细菌都将存活下来。为了各种非医疗的目的而使用的抗生素也会造成耐药菌株的增加。例如，若使细菌不断地接触添加到洗手皂、清洁剂、洗涤剂和家畜饲料中的少量抗生素，耐药菌就会存活下来。

 Antibiotic resistance is especially dangerous with infectious diseases that are pervasive and easily spread. Diseases like tuberculosis, malaria, and childhood ear infections have become very difficult to treat. Tuberculosis cases in the US were nearly eliminated with the 1940 discovery of isoniazid, but are on the rise again, due to the emergence of resistant strains that can only be treated with less effective drugs. Nearly 2 million patients each year contract bacterial infections during a hospital stay. Staphylococcus aureus is commonly found in hospitals and infects patients with weakened immune systems causing blood poisoning and pneumonia. Strains have been isolated that are resistant to methicillin, oxacillin, penicillin, amoxicillin, and even vancomycin, an antibiotic used when other options fail. The prevalence of antibiotics and antibacterial cleaners in hospitals means that more than 70% of hospital acquired infections in the US are resistant to at least one antibiotic.

 细菌的耐药性对于普遍存在而易于传播的传染病来说是特别危险的。像肺结核、疟疾和儿童耳部感染都已经变得非常难以治疗。1940年，随着异烟肼的发现，美国的肺结核病几乎被扫光，但是现在该病病例又正在呈现出上升的趋势，就是因为出现了只能利用疗效较差的药物进行治疗的耐药菌株。每年有将近两百万病人在住院期间遭受细菌感染。金黄色葡萄球菌通常存在于医院中，感染那些免疫系统变差的病人，引起败血症和肺炎。菌株已经被分离出来，它们对甲氧西林、苯唑西林、青霉素、阿莫西林都具有耐药性，甚至对万古霉素也有耐药性，而万古霉素是选择其他抗生素都无效的时候才使用的一种抗生素。抗生素和抗菌清洁剂在医院里的普遍使用，意味着美国70%以上遭受感染的医院至少对于一种抗生素具有耐药性。

 2.Mechanism of Antibiotic Resistance

 2. 细菌的耐药机制

 Bacteria acquire resistance in a variety of ways. In some cases, enzymes native to the bacteria develop the ability to inactivate antibiotics before they have a chance to work. It is also common for the actual target molecule in the bacteria to be altered so the drug cannot bind to it, or that bacteria can find a means other than an affected metabolic pathway to obtain a necessary metabolite. Finally, resistance can occur if the bacteria find a way to prevent the drug from accumulating in the cell either by preventing it from getting in or increasing the rate that it is expelled.

 细菌通过各种各样的途径来获得耐药性。在某些情况中，细菌本身的酶产生了使抗生素丧失活性的能力，抗生素失去活性之后，细菌再择机而动。这样的情况也常见：细菌中实际的靶分子被改变，药物无法粘附其上，或者细菌可以找到一种途径来获得必要的代谢物，避开遭受侵袭的代谢通道。如果细菌通过阻拦药物的进入或降低被排斥的速度，找到了制止药物在细胞内积累的途径，那么最终耐药性就产生了。

 Regardless of the mechanism of resistance, it is always genetically encoded. Some bacteria naturally have so-called “resistance genes”, in fact, bacteria found frozen in a glacier for 2,000 years were found to have some antibiotic resistance. Many bacteria and fungi produce antibiotic compounds to protect themselves from other microbes, and as a result, some of these microbes have evolved to be resistant to them. Resistance genes can also result from spontaneous mutations and can be passed on to other bacteria through normal genetic exchange processes.  For example, bacterial cells can often transfer a circular strand of DNA outside of its own chromosome (called a plasmid) to another bacterium through a process called conjugation. Similarly, bacteria can acquire genes released from dead bacteria and incorporate them into their chromosome or plasmid through a process called transformation. Finally, in a process called transduction, a bacterial virus called a bacteriophage invades a cell and removes genetic material. When the bacteriophage infects another cell, that gene can be incorporated into its chromosome or plasmid.

 尽管细菌拥有耐药机制，但是对各种机制通常进行基因编码。一些细菌天生就有所谓的“耐药基因”。实际上，在一条冰川中所发现的封冻了2000的细菌，对某些抗生素具有耐药性。许多细菌和真菌都产生抗生化合物，可以保护自己不受其他微生物的侵袭，结果一些微生物通过进化表现出对这些抗生化合物的耐药性。耐药基因也可以产生于自发突变，然后通过正常的基因交流过程被传递到其他细菌中。例如，细菌细胞常常通过一个叫做“接合”的过程可以把染色体之外的一种环状DNA链（被称为“质粒”）转移到另外一个细菌上。同样，细菌通过一个叫做“转化”的过程获得死亡细菌释放的基因，并且将这些基因并入自己的染色体或质粒之中。还有，在一个被称为“转导”的过程中，一种叫做噬菌体的细菌病毒可以侵入细胞，并将其基因材料剔除。当噬菌体感染另外一个细胞时，该细胞的基因会被整合纳入噬菌体的染色体或质粒之中。

 3. Multiple Drug Resistance

 3.多重耐药性

 With each passing decade, bacteria that are resistant to multiple antibiotics have become increasingly common. Until recently, if an infection proved resistant to first-line therapy, an alternative or combination was generally available. This is no longer the case.

 随着时间的推移，对多种抗生素耐药的细菌越来越常见了。不久前，如果一种感染对一线的药物疗法表现出耐药性，通常可以选择一种替代药物或实施联合用药。但是，现在情况已经不是这样了。

 According to the U.S. Centers for Disease Control (“CDC”), the emergence and re-emergence of infectious disease organisms contributed to a 58% increase in U.S. per capita mortality from infectious diseases between 1980 and 1992, making infection the third leading cause of death, behind heart disease and cancer. The incidence of drug-resistant infections is reaching crisis levels in many hospitals, in part because antibiotic resistant organisms frequently lurk in the hospital setting.

 根据美国疾病控制中心（CDC）提供的数据，在1980ian到1992年之间，由于传染病菌的出现和反复出现，传染病的平均死亡率上升了58%，使传染病成为心脏病和癌症之后的第三大杀手。在许多医院里，耐药性感染达到了危机的地步，部分原因是耐药细菌常常潜伏在医院环境中。

 In hospitals, Methicillin resistant Staphylococcus aureus (“MRSA”) has become resistant to nearly all antibiotics. Vancomycin has become the drug of last resort to treat this problem. Vancomycin resistant Enterococcus (“VRE”) strains have also emerged as untreatable disease agents. Since vancomycin resistance is transferable, there is high expectation that the trait will move to S. aureus. Already, strains of MRSA insensitive to vancomycin have appeared, where lack of an antibiotic to treat has been associated with patient deaths. In recent years, the imminent threat to public health from untreatable infectious diseases has attracted the attention of clinicians, microbiologists, and the popular press.

 在医院里，耐甲氧西林金黄色葡萄球菌（MRSA）对几乎所有的抗生素都表现出耐药性。万古霉素成为治疗这种疾病最终采用的手段。此外，耐万古霉素肠球菌（VRE）菌株作为一种无法医治的病原已经出现。由于对万古霉素的耐药性是可以转移的，这种耐药性很可能会转移到金黄色葡萄球菌上。对万古霉素不敏感的MRSA菌株已经出现，由于缺乏可用以治病抗生素已经造成了病人死亡。近年来，不可医治的传染病对公众健康造成的紧迫威胁引起了临床医生、微生物学家以及大众媒体的关注。

4. Control Measures

4.控制措施

To limit the development of antibiotic resistance, one should:

  为了控制细菌耐药性继续发展，针对个人的几点建议如下：

 1）Use antibiotics only for bacterial infections

 1）只有在细菌感染时才使用抗生素。

 2）Identify the causative organism if possible

 2）如果可能的话，要识别致病菌。

 3）Use the right antibiotic; do not rely on broad-range antibiotics

 3）使用对症的抗生素，不要依赖广谱抗生素。

 4）Not stop antibiotics as soon as symptoms improve; finish the full course

 4）不要症状一减轻就停用抗生素，要在整个疗程中坚持用药。

 5） Not use antibiotics for most colds, coughs, bronchitis, sinus infections, and eye infections, which are caused by viruses.

 5) 对于多数感冒、咳嗽、支气管炎、鼻窦感染和眼部感染，不要使用抗生素，这些都有可能是病毒引起的。

It is argued that government legislation will aid in educating the public on the importance of restrictive use of antibiotics, not only for human clinical use but also for treating animals raised for human consumption.

 有人认为政府的立法将会有助于使公众认识到限制滥用抗生素的重要性，这种限制不但针对人类的临床应用，还要针对以人类消费为目的所饲养的动物用药。