胡德良 譯
| 1.Resistant Bacteria | 1. 耐藥菌 |
| 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. | 抗生素應(yīng)用和濫用的不斷增加導(dǎo)致了耐藥的病原菌株數(shù)量不斷上升，引起了嚴(yán)重的公共健康問題。亞歷山大·弗萊明是最早對抗生素問題表示關(guān)心的人之一，他強(qiáng)調(diào)了濫用抗生素會導(dǎo)致耐藥性。1945年，弗萊明在接受諾貝爾獎(jiǎng)時(shí)，他是以告誡的話語來結(jié)束演講的：“但是，我要提出一條警告……在實(shí)驗(yàn)室里使細(xì)菌對青霉素耐藥并不難，只要將它們暴露于藥物濃度不足以殺死它們的環(huán)境即可，而同樣的耐藥情況偶爾也發(fā)生在人體中。”隨著他的警告，耐藥菌株感染的情況也開始增加了。根據(jù)一家醫(yī)院的報(bào)告，耐青霉素金黃色葡萄球菌的感染率從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.
在抗生素治療方面，理想的劑量和療程將會殺死所有的敏感細(xì)菌，而產(chǎn)生耐藥性的幾率會最小。當(dāng)利用抗生素治療細(xì)菌感染的時(shí)候，特別是如果給藥劑量太小或療程太短的話，任何產(chǎn)生耐藥性的細(xì)菌都將存活下來。為了各種非醫(yī)療的目的而使用的抗生素也會造成耐藥菌株的增加。例如，若使細(xì)菌不斷地接觸添加到洗手皂、清潔劑、洗滌劑和家畜飼料中的少量抗生素，耐藥菌就會存活下來。
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.
細(xì)菌的耐藥性對于普遍存在而易于傳播的傳染病來說是特別危險(xiǎn)的。像肺結(jié)核、瘧疾和兒童耳部感染都已經(jīng)變得非常難以治療。1940年，隨著異煙肼的發(fā)現(xiàn)，美國的肺結(jié)核病幾乎被掃光，但是現(xiàn)在該病病例又正在呈現(xiàn)出上升的趨勢，就是因?yàn)槌霈F(xiàn)了只能利用療效較差的藥物進(jìn)行治療的耐藥菌株。每年有將近兩百萬病人在住院期間遭受細(xì)菌感染。金黃色葡萄球菌通常存在于醫(yī)院中，感染那些免疫系統(tǒng)變差的病人，引起敗血癥和肺炎。菌株已經(jīng)被分離出來，它們對甲氧西林、苯唑西林、青霉素、阿莫西林都具有耐藥性，甚至對萬古霉素也有耐藥性，而萬古霉素是選擇其他抗生素都無效的時(shí)候才使用的一種抗生素。抗生素和抗菌清潔劑在醫(yī)院里的普遍使用，意味著美國70%以上遭受感染的醫(yī)院至少對于一種抗生素具有耐藥性。
2.Mechanism of Antibiotic Resistance
2. 細(xì)菌的耐藥機(jī)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.
細(xì)菌通過各種各樣的途徑來獲得耐藥性。在某些情況中，細(xì)菌本身的酶產(chǎn)生了使抗生素喪失活性的能力，抗生素失去活性之后，細(xì)菌再擇機(jī)而動(dòng)。這樣的情況也常見：細(xì)菌中實(shí)際的靶分子被改變，藥物無法粘附其上，或者細(xì)菌可以找到一種途徑來獲得必要的代謝物，避開遭受侵襲的代謝通道。如果細(xì)菌通過阻攔藥物的進(jìn)入或降低被排斥的速度，找到了制止藥物在細(xì)胞內(nèi)積累的途徑，那么最終耐藥性就產(chǎn)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.
盡管細(xì)菌擁有耐藥機(jī)制，但是對各種機(jī)制通常進(jìn)行基因編碼。一些細(xì)菌天生就有所謂的“耐藥基因”。實(shí)際上，在一條冰川中所發(fā)現(xiàn)的封凍了2000的細(xì)菌，對某些抗生素具有耐藥性。許多細(xì)菌和真菌都產(chǎn)生抗生化合物，可以保護(hù)自己不受其他微生物的侵襲，結(jié)果一些微生物通過進(jìn)化表現(xiàn)出對這些抗生化合物的耐藥性。耐藥基因也可以產(chǎn)生于自發(fā)突變，然后通過正常的基因交流過程被傳遞到其他細(xì)菌中。例如，細(xì)菌細(xì)胞常常通過一個(gè)叫做“接合”的過程可以把染色體之外的一種環(huán)狀DNA鏈（被稱為“質(zhì)?！保┺D(zhuǎn)移到另外一個(gè)細(xì)菌上。同樣，細(xì)菌通過一個(gè)叫做“轉(zhuǎn)化”的過程獲得死亡細(xì)菌釋放的基因，并且將這些基因并入自己的染色體或質(zhì)粒之中。還有，在一個(gè)被稱為“轉(zhuǎn)導(dǎo)”的過程中，一種叫做噬菌體的細(xì)菌病毒可以侵入細(xì)胞，并將其基因材料剔除。當(dāng)噬菌體感染另外一個(gè)細(xì)胞時(shí)，該細(xì)胞的基因會被整合納入噬菌體的染色體或質(zhì)粒之中。
3.多重耐藥性
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.
隨著時(shí)間的推移，對多種抗生素耐藥的細(xì)菌越來越常見了。不久前，如果一種感染對一線的藥物療法表現(xiàn)出耐藥性，通常可以選擇一種替代藥物或?qū)嵤┞?lián)合用藥。但是，現(xiàn)在情況已經(jīng)不是這樣了。
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.
根據(jù)美國疾病控制中心（CDC）提供的數(shù)據(jù)，在1980ian到1992年之間，由于傳染病菌的出現(xiàn)和反復(fù)出現(xiàn)，傳染病的平均死亡率上升了58%，使傳染病成為心臟病和癌癥之后的第三大殺手。在許多醫(yī)院里，耐藥性感染達(dá)到了危機(jī)的地步，部分原因是耐藥細(xì)菌常常潛伏在醫(yī)院環(huán)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.
在醫(yī)院里，耐甲氧西林金黃色葡萄球菌（MRSA）對幾乎所有的抗生素都表現(xiàn)出耐藥性。萬古霉素成為治療這種疾病最終采用的手段。此外，耐萬古霉素腸球菌（VRE）菌株作為一種無法醫(yī)治的病原已經(jīng)出現(xiàn)。由于對萬古霉素的耐藥性是可以轉(zhuǎn)移的，這種耐藥性很可能會轉(zhuǎn)移到金黃色葡萄球菌上。對萬古霉素不敏感的MRSA菌株已經(jīng)出現(xiàn)，由于缺乏可用以治病抗生素已經(jīng)造成了病人死亡。近年來，不可醫(yī)治的傳染病對公眾健康造成的緊迫威脅引起了臨床醫(yī)生、微生物學(xué)家以及大眾媒體的關(guān)注。
4. Control Measures
4.控制措施
To limit the development of antibiotic resistance, one should:
為了控制細(xì)菌耐藥性繼續(xù)發(fā)展，針對個(gè)人的幾點(diǎn)建議如下：
1）Use antibiotics only for bacterial infections
1）只有在細(xì)菌感染時(shí)才使用抗生素。
2）Identify the causative organism if possible
2）如果可能的話，要識別致病菌。
3）Use the right antibiotic; do not rely on broad-range antibiotics
3）使用對癥的抗生素，不要依賴廣譜抗生素。
4）Not stop antibiotics as soon as symptoms improve; finish the full course
4）不要癥狀一減輕就停用抗生素，要在整個(gè)療程中堅(jiān)持用藥。
5） Not use antibiotics for most colds, coughs, bronchitis, sinus infections, and eye infections, which are caused by viruses.
5) 對于多數(shù)感冒、咳嗽、支氣管炎、鼻竇感染和眼部感染，不要使用抗生素，這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.
有人認(rèn)為政府的立法將會有助于使公眾認(rèn)識到限制濫用抗生素的重要性，這種限制不但針對人類的臨床應(yīng)用，還要針對以人類消費(fèi)為目的所飼養(yǎng)的動(dòng)物用藥。
