Antibiotics won the battle against resistant bacteria, but they may not win the war.

抗生素曾贏得了對抗耐藥細菌的戰(zhàn)斗，但它們可能不能再贏得這場戰(zhàn)爭了。

You probably know that antibiotic-resistant bacteria, also known as superbugs, have hampered physicians’ ability to treat infections. You may also be aware that there has been a steep decline in the number of new antibiotics coming to market.

你可能知道耐抗生素細菌，也被稱為超級細菌，已經(jīng)阻礙了醫(yī)生治療感染的能力。你可能也意識到，市場上新抗生素的數(shù)量急劇下降。

Some headlines suggest humanity is doomed by antimicrobial resistance; even politicians and governments have weighed in, comparing rising antimicrobial resistance to other popular crises such as climate change. Although I believe these assertions are exaggerated, antimicrobial resistance is a serious problem.

一些頭條新聞表明，人類注定要遭受抗生素耐藥性;甚至政治家和政府也參與進來，將不斷增長的抗生素耐藥性與氣候變化等其他常見危機進行了比較。盡管我認為這些斷言有些夸張，但抗生素耐藥性是一個嚴重的問題。

I am a physician scientist with a specialty in infectious diseases. I have been fascinated by the role that bacteria play in human health, and the potential for using viruses to treat bacterial infections.

我是一名醫(yī)學科學家，專攻傳染病。我一直著迷于細菌在人類健康中所扮演的角色，以及利用病毒治療細菌感染的潛力。

What causes antimicrobial resistance?

是什么導致了抗生素耐藥性?

One significant factor contributing to antimicrobial resistance is the excessive use of antibiotics. In the U.S., where antibiotics are widely available, some patients demand these drugs for many different illnesses. Many physicians appease their patients because they don’t understand when and when not to use them and because there is no regulatory structure to limit their use. Anyone with a prescription pad can prescribe any antibiotic to treat any condition and rarely, if ever, face any consequences. There are some efforts to reduce antibiotic use, but the scope of the problem in the U.S. remains large.

過度使用抗生素是造成抗生素耐藥性的一個重要因素。在美國在美國，抗生素隨處可見，一些病人需要這些藥物治療許多不同的疾病。許多醫(yī)生安撫他們的病人，因為他們不知道什么時候不使用，什么時候不使用，也因為沒有監(jiān)管結構來限制他們的使用。任何拿著處方箋的人都可以用任何抗生素來治療任何疾病，而且很少會面臨任何后果。雖然已經(jīng)采取了一些措施來減少抗生素的使用，但在美國，這個問題的范圍仍然很大。

Some countries, such as Sweden, use incentives to encourage doctors to improve antibiotic uses. But there is no counterpart for this system in U.S. hospitals and clinics.

一些國家，如瑞典，使用激勵措施來鼓勵醫(yī)生改進抗生素的使用。但在美國的醫(yī)院和診所里，還沒有類似的系統(tǒng)。

The problem goes beyond humans; 70 percent of all antibiotics are actually used on animals. This means that humans can be exposed to antibiotics by just handling animal products. The drumstick you are preparing for dinner might also have antibiotic-resistant bacteria tagging along.

這個問題不僅限于人類;事實上，70%的抗生素都是用在動物身上的。這意味著人類只要接觸動物產(chǎn)品就能接觸到抗生素。你正在準備晚餐的雞腿上也可能有耐抗生素細菌。

Once antimicrobial resistance develops in a bacterium, it doesn’t always go away. For example, methicillin-resistant Staphylococcus aureus (MRSA) evolved resistance to multiple different antibiotics; yet, despite efforts to reduce its spread by limiting the use of antibiotics that led to its emergence, MRSA still persists in hospitals and the community.

一旦細菌產(chǎn)生了抗菌素耐藥性，它并不總是消失。例如，耐甲氧西林的金黃色葡萄球菌(MRSA)進化出對多種不同抗生素的耐藥性;然而，盡管通過限制抗生素（導致MRSA出現(xiàn)）的使用來減少其傳播，MRSA仍然在醫(yī)院和社區(qū)中存在。

An alternative to antibiotics

抗生素的替代品

Another reason for finding alternatives to antibiotics is that we share our microbes with the people and pets who live around us; thus, others can acquire one of these superbugs without ever taking an antibiotic.

尋找抗生素替代品的另一個原因是，我們與生活在我們身邊的人和寵物分享我們的微生物;因此，其他人無需服用抗生素就能感染這些超級細菌。

A not-so-obvious reason for developing new therapies is that our bodies are home to a large community of microorganisms, including bacteria, called our microbiome. These microorganisms are necessary to maintain our health. Those same antibiotics that kill harmful bacteria also kill the good ones.

開發(fā)新療法的一個不太明顯的原因是，我們的身體是一個大的微生物群落的家園，包括細菌，被稱為我們的微生物群落。這些微生物是維持我們健康所必需的。殺死有害細菌的抗生素也會殺死有益細菌。

There is an alternative to antibiotics, but it was dismissed by medicine years ago.

有一種抗生素的替代品，但多年前被醫(yī)學界所摒棄。

The original phage therapy story

最初的噬菌體治療故事

That alternative was something called phage therapy, which uses viruses that infect bacteria, called bacteriophages, to kill disease-causing bacteria. Bacteriophages, or phages, were used frequently in the early- and pre- antibiotic eras between the 1920s and ‘40s to treat life-threatening infections.

另一種方法叫做噬菌體療法，它使用感染細菌的病毒，即噬菌體，來殺死致病細菌。噬菌體，在20世紀20年代至40年代的早期和前抗生素時代被頻繁地用于治療危及生命的感染。

But phage therapy had many disadvantages. The first was that phages were unpredictable. One type of phage might wipe out the bad bacteria in one individual but not another’s. So hospitals had to keep a broad collection of phages to kill disease-causing bacteria from all their patients. An antibiotic such as vancomycin, by comparison, predictably kills entire groups of bacteria.

但是噬菌體療法有很多缺點。首先，噬菌體是不可預測的。一種噬菌體可以消滅一個人體內的有害細菌，但不能消滅另一個人體內的。因此，醫(yī)院不得不大量收集噬菌體，以殺死所有病人身上的致病細菌。相比之下，萬古霉素等抗生素可預見地殺死整群細菌。

Another downside is that phage collections require maintenance. So not only did hospitals have to keep a large variety of phages on hand, but they had to keep them in shape. So medicine chose antibiotics for convenience, and hadn’t looked back in any meaningful way, until recently.

另一個缺點是噬菌體收集需要維護。因此，醫(yī)院不僅要保存大量的噬菌體，而且還要保持它們的形狀。所以醫(yī)學為了方便而選擇了抗生素，直到最近才以任何有意義的方式回顧過去。

Making a comeback?
So, why is phage therapy making a comeback? Antibiotic resistance is an obvious answer, but doesn’t explain the full story.

卷土重來?
那么，為什么噬菌體療法會卷土重來呢?抗生素耐藥性是一個顯而易見的答案，但并不能解釋全部情況。

As a specialist in infectious diseases, I have been interested in phage therapy as long as I can remember, but only recently have I felt comfortable saying this out loud. Why? A physician might be considered a “quack” just for mentioning phage therapy because the early attempts were neither a rousing success or a colossal failure. Like any therapeutic, it had its strengths and weaknesses.

作為一名傳染病專家，我從記事起就對噬菌體治療很感興趣，但直到最近，我才覺得把這句話大聲說出來很舒服。為什么?僅僅因為提到噬菌體治療，醫(yī)生就可能被認為是“江湖醫(yī)生”，因為早期的嘗試既沒有令人振奮的成功，也沒有巨大的失敗。和任何治療方法一樣，它也有自己的優(yōu)缺點。

However, now scientific advances can guide us toward which phage is best for destroying a particular microbe. With the rising antimicrobial resistance crisis, physicians and scientists have a well-timed opportunity to work together to develop effective phage therapies.

然而，現(xiàn)在科學的進步可以引導我們找到哪種噬菌體最適合消滅一種特定的微生物。隨著抗生素耐藥性危機的加劇，醫(yī)生和科學家有了一個很好的時機來共同開發(fā)有效的噬菌體療法。

The proof of this comes from recent landmark phage therapy cases. The successful treatment of a physician with a life-threatening infection and a grave prognosis caused by a multi-drug resistant bacterium at my institution serves as a great example. Another pivotal case circulating in popular media has kept this trend going. We physicians may be able to treat just about any disease-causing bacterium; it is just a matter of finding a suitable phage.

這一點的證據(jù)來自最近具有里程碑意義的噬菌體治療案例。我所在的機構成功地治療了一名因多重耐藥細菌引起的危及生命的感染和嚴重預后的醫(yī)生，這是一個很好的例子。另一個在大眾媒體上流傳的關鍵案例使這一趨勢得以延續(xù)。我們醫(yī)生也許能夠治療任何致病細菌；這只是找到一個合適的噬菌體的問題。

A big part of phage therapy research is devoted to “phage hunting,” where we microbiologists scour the soil, the oceans and the human body to identify phages with the potential to kill the bacteria that ail us. While the pace of these studies has been slow, the new research is revealing the therapeutic potential of phages in medicine.

噬菌體治療研究的很大一部分致力于“噬菌體狩獵”，在那里，我們微生物學家仔細研究土壤、海洋和人體，以確定具有殺死困擾我們的細菌潛力的噬菌體。盡管這些研究進展緩慢，但新的研究揭示了噬菌體在醫(yī)學上的治療潛力。

You might think that with all the phage hunting and landmark cases that we would start using phage therapy all the time, but we don’t.

你可能認為在所有的噬菌體狩獵和具有里程碑意義的案例中，我們會一直使用噬菌體療法，但我們沒有。

The case for using phages

使用噬菌體的例子

One advantage of antibiotics is that since they have been used for decades, we know a lot about their safety. Physicians make simple calculations every day about the risk-benefit ratio of using antibiotics, but aren’t equipped to make the same calculations about phages. Does anyone really want a doctor injecting them with a virus to cure a bacterial infection? I doubt that would be anyone’s choice when the question is posed that way.

抗生素的一個優(yōu)點是，由于它們已經(jīng)使用了幾十年，我們對它們的安全性有了很多了解。醫(yī)生們每天都會對使用抗生素的風險-收益比進行簡單的計算，但卻沒有能力對噬菌體進行相同的計算。真的有人想讓醫(yī)生給他們注射病毒來治療細菌感染嗎?當問題以這種方式提出時，我懷疑這不是任何人的選擇。

But, remember that phages are natural. They’re on every surface of your body. They are in the ocean and soil, and in your toilet and sink. They are literally everywhere. Thus, putting a phage into your body to kill a bacterium quite frankly is something that nature does to us every single day, and as far as we know, we are no worse for the wear.

但是，請記住噬菌體是自然形成的。它們在你身體的每一個表面。它們在海洋和土壤里，在你的馬桶和水槽里。它們確實無處不在。因此，將噬菌體放入體內殺死細菌是大自然每天都在做的事情，據(jù)我們所知，我們的身體并沒有因此而受損。

Phages are estimated to kill half the world’s bacteria every 48 hours and are probably the most potent antibacterial agents out there. Is there really a compelling reason to be concerned when a doctor gives us a phage instead of us acquiring that same phage from our sink at home? Only time will tell. Unfortunately, as antimicrobial resistance continues to rise, time may not be on our side.

據(jù)估計，噬菌體每48小時就能殺死世界上一半的細菌，而且可能是最有效的抗菌劑。當醫(yī)生給我們一種噬菌體而不是我們從家里的水槽中獲得同樣的噬菌體時，我們真的有一個令人信服的理由擔心嗎?只有時間才能證明。不幸的是，隨著抗菌素耐藥性繼續(xù)上升，時間可能不會站在我們這一邊。

（評論部分）

Jon Richfield
I am a great fan of phages and the potential for engineering them, using them not only against bacteria, but also fungi, and possibly even some of the larger viruses, but it seems to me that their use in combination with some of the antibacterial chemicals such as antibiotics, should be of interest as well.
For example, if an antibiotic excludes or reduces the risk of secondary infections while the phage controls a primary infection of plague or TB, or kills an emerging strain of antibiotic-resistant bacteria during phage treatment, that might be of value, shouldn’t it?

我非常喜歡噬菌體，和其工程改造的潛力，不僅可以對抗細菌，還可以對抗真菌，甚至可能是一些更大的病毒，但在我看來，它們與抗生素等抗菌化學物質的結合使用也應該引起人們的興趣。
例如，如果一種抗生素排除或降低了繼發(fā)性感染的風險，而噬菌體控制了鼠疫或結核病的一次感染，或者在噬菌體治療期間殺死了一種新出現(xiàn)的耐抗生素細菌，這可能是有價值的，不是嗎?

David Pride（作者回復）
加州大學圣地亞哥分校微生物學副主任

That is a major area of research in which phages are used. In fact, in a lot of phage studies, they are used in combination with antibiotics because the antibiotics are the standard of care. It can make it difficult to figure out how much improvement was seen due to the phage and how much of the improvement was due to the antibiotics.

這是噬菌體應用的一個主要研究領域。事實上，在許多噬菌體研究中，它們與抗生素結合使用，因為抗生素是治療的標準。這使得我們很難弄清楚噬菌體的作用有多大，以及抗生素的作用有多大。

In a lot of the more recent cases, it is more obvious that the phage is moving the needle even if it is receiving an assist from the antibiotic. The immediate future of phage therapy will probably involve phages, antibiotics, and the human immune system, with the hope to eliminate the antibiotics from that equation

在最近的許多病例中，更明顯的是噬菌體在移動針頭，即使它得到了抗生素的幫助。在不久的將來，噬菌體治療可能會涉及噬菌體、抗生素和人類免疫系統(tǒng)，希望將抗生素從這個等式中消除。

——————分割線——————

Robert Ferguson
Thank you David; that is encouraging.
I remember reading about this c50years ago. It was pioneered in Russia, I believe. In Moscow they had a huge collection of specifis bacteriophage virus samples. It was the future, i believed then. WELL DONE RUSSIA!!!

謝謝你大衛(wèi)，這是令人鼓舞的。我記得50年前讀過這篇文章。我相信它是在俄羅斯開創(chuàng)的。在莫斯科，他們收集了大量的噬菌體病毒樣本。我當時相信這就是未來。干得好俄羅斯！

David Pride（作者回復）

Yes. This geographic area was a hotbed of phage therapy research. The study of phage therapy continues in some Eastern European countries that were a part of the Soviet Union.

是的。這個地理區(qū)域是噬菌體治療研究的溫床。噬菌體療法的研究仍在前蘇聯(lián)的一些東歐國家進行。

Robert Ferguson（回復樓上）
I used “Russia” because US people usually simplified USSR to that AND it was Moscow the “Ark” of viruses was held. 50 years ago? USA dates and progress then would be helpfull. I’ll do some research. Why, if US research on phages was so advanced and is now found to be efficacious potentially, was there not a massive progress made in that time in the most advanced and richest country ever?

我用“俄羅斯”是因為美國人通常把蘇聯(lián)簡化成“俄羅斯”，而病毒的“方舟”就在莫斯科。50年前？美國的日期和進展將是有幫助的。我會做一些調查。如果美國對噬菌體的研究如此先進，而且現(xiàn)在被發(fā)現(xiàn)具有潛在的有效性，那么在那個有史以來最發(fā)達和最富有的國家，為什么沒有取得巨大的進展嗎?

——————分割線——————

Alvaro Ferreira Junior
congratulations for your elegant text. I was surprised with high use of antibiotics in animals. I want to know your some opinion about the use of phages against bacteria in farm animals.

祝賀你優(yōu)美的文字。我對動物中抗生素的大量使用感到驚訝。我還想知道你對在農場動物身上使用噬菌體對抗細菌有何看法。