How can we solve the antibiotic resistance crisis Gerry Wright

Antibiotics: behind the scenes,
they enable much of modern medicine.

We use them to cure infectious diseases,

but also to safely facilitate everything
from surgery to chemotherapy

to organ transplants.

Without antibiotics,

even routine medical procedures
can lead to life-threatening infections.

And we’re at risk of losing them.

Antibiotics are chemicals
that prevent the growth of bacteria.

Unfortunately, some bacteria
have become resistant

to all currently available antibiotics.

At the same time,
we’ve stopped discovering new ones.

Still, there’s hope that we can get ahead
of the problem.

But first, how did we
get into this situation?

The first widely used antibiotic
was penicillin,

discovered in 1928 by Alexander Fleming.

In his 1945 Nobel Prize
acceptance speech,

Fleming warned that bacterial resistance
had the potential to ruin

the miracle of antibiotics.

He was right: in the 1940s and 50s,

resistant bacteria
already began to appear.

From then until the 1980s,

pharmaceutical companies
countered the problem of resistance

by discovering many new antibiotics.

At first this was a highly successful—
and highly profitable— enterprise.

Over time, a couple things changed.

Newly discovered antibiotics
were often only effective

for a narrow spectrum of infections,

whereas the first ones
had been broadly applicable.

This isn’t a problem in itself,

but it does mean that fewer doses
of these drugs could be sold—

making them less profitable.

In the early days,
antibiotics were heavily overprescribed,

including for viral infections
they had no effect on.

Scrutiny around prescriptions increased,
which is good, but also lowered sales.

At the same time,
companies began to develop more drugs

that are taken over a patient’s lifetime,

like blood pressure
and cholesterol medications,

and later anti-depressants
and anti-anxiety medications.

Because they are taken indefinitely,
these drugs more profitable.

By the mid-1980s, no new chemical classes
of antibiotics were discovered.

But bacteria continued to acquire
resistance and pass it along

by sharing genetic information
between individual bacteria

and even across species.

Now bacteria that are resistant
to many antibiotics are common,

and increasingly some strains
are resistant to all our current drugs.

So, what can we do about this?

We need to control the use
of existing antibiotics, create new ones,

combat resistance to new
and existing drugs,

and find new ways to fight
bacterial infections.

The largest consumer
of antibiotics is agriculture,

which uses antibiotics not only
to treat infections

but to promote the growth of food animals.

Using large volumes of antibiotics

increases the bacteria’s exposure
to the antibiotics

and therefore their opportunity
to develop resistance.

Many bacteria that are common in animals,
like salmonella, can also infect humans,

and drug-resistant versions can pass
to us through the food chain

and spread through international trade
and travel networks.

In terms of finding new antibiotics,

nature offers the most promising
new compounds.

Organisms like other microbes and fungi
have evolved over millions of years

to live in competitive environments—

meaning they often contain
antibiotic compounds

to give them a survival advantage
over certain bacteria.

We can also package antibiotics
with molecules that inhibit resistance.

One way bacteria develop resistance
is through proteins of their own

that degrade the drug.

By packaging the antibiotic with molecules
that block the degraders,

the antibiotic can do its job.

Phages, viruses that attack bacteria
but don’t affect humans,

are one promising new avenue
to combat bacterial infections.

Developing vaccines for common infections,
meanwhile,

can help prevent disease
in the first place.

The biggest challenge to all
these approaches is funding,

which is woefully inadequate
across the globe.

Antibiotics are so unprofitable
that many large pharmaceutical companies

have stopped trying to develop them.

Meanwhile, smaller companies
that successfully bring new antibiotics

to market often still go bankrupt,
like the American start up Achaogen.

New therapeutic techniques
like phages and vaccines

face the same fundamental problem
as traditional antibiotics:

if they’re working well,
they’re used just once,

which makes it difficult to make money.

And to successfully counteract resistance
in the long term,

we’ll need to use
new antibiotics sparingly—

lowering the profits
for their creators even further.

One possible solution is to shift profits
away from the volume of antibiotics sold.

For example, the United Kingdom
is testing a model

where healthcare providers
purchase antibiotic subscriptions.

While governments are looking for ways
to incentivize antibiotic development,

these programs are still
in the early stages.

Countries around the world
will need to do much more—

but with enough investment
in antibiotic development

and controlled use of our current drugs,

we can still get ahead of resistance.

抗生素:在幕后,
它们使现代医学发挥了很大作用。

我们用它们来治疗传染病,

也可以安全地促进
从手术到化疗

再到器官移植的一切。

如果没有抗生素,

即使是常规医疗程序
也可能导致危及生命的感染。

我们有失去它们的风险。

抗生素是
防止细菌生长的化学物质。

不幸的是,一些细菌
已经

对所有目前可用的抗生素产生抗药性。

同时,
我们已经停止发现新的。

尽管如此,我们还是有希望
解决这个问题。

但首先,我们是
如何陷入这种境地的?

第一种广泛使用的抗生素
是青霉素,

由亚历山大·弗莱明于 1928 年发现。 弗莱明

在 1945 年的诺贝尔奖
获奖感言中

警告说,细菌耐药性
有可能毁掉

抗生素的奇迹。

他是对的:在 1940 年代和 50 年代,

耐药细菌
已经开始出现。

从那时到 1980 年代,

制药公司

通过发现许多新的抗生素来应对耐药性问题。

起初,这是一家非常成功
且利润丰厚的企业。

随着时间的推移,一些事情发生了变化。

新发现的
抗生素通常只

对狭窄范围的感染有效,

而第一个抗生素
则广泛适用。

这本身不是问题,

但这确实意味着
可以出售的这些药物的剂量会减少——这会

降低它们的利润。

在早期,
抗生素被严重过度使用,

包括对
它们没有影响的病毒感染。

对处方的审查增加了,
这很好,但也降低了销售额。

与此同时,
公司开始开发更多

可在患者一生中

服用的药物,如血压和胆固醇药物,

以及后来的抗抑郁药
和抗焦虑药物。

因为它们是无限期服用,
这些药物更有利可图。

到 1980 年代中期,没有发现新的化学
类抗生素。

但是细菌继续获得
抗性并通过

在个体细菌

之间甚至跨物种之间共享遗传信息来传递它。

现在,
对许多抗生素有抗药性的细菌很常见,

而且越来越多的一些菌株
对我们目前所有的药物都有抗药性。

那么,我们能做些什么呢?

我们需要控制
现有抗生素的使用,创造新的抗生素,

对抗对
新药和现有药物的耐药性,

并找到对抗
细菌感染的新方法。 抗生素

的最大消费者
是农业,

它使用抗生素不仅
可以治疗感染,

还可以促进食用动物的生长。

使用大量抗生素会

增加细菌对抗生素的接触

,从而增加它们
产生抗药性的机会。

许多动物中常见的细菌,
如沙门氏菌,也可以感染人类

,耐药菌可以
通过食物链传给我们,

并通过国际贸易
和旅行网络传播。

在寻找新抗生素方面,

大自然提供了最有希望的
新化合物。

像其他微生物和真菌
这样的生物已经进化了数百万年,

可以生活在竞争环境中——

这意味着它们通常含有
抗生素化合物

,使它们
比某些细菌具有生存优势。

我们还可以
用抑制耐药性的分子包装抗生素。

细菌产生耐药性的一种方式
是通过它们自身的

蛋白质降解药物。

通过用
阻止降解剂的分子包装抗生素

,抗生素可以发挥作用。

噬菌体是一种攻击细菌
但不影响人类的病毒,

是对抗细菌感染的一种有希望的新
途径。 与此同时,

开发针对常见感染的疫苗

可以帮助预防
疾病。

所有这些方法的最大挑战
是资金,


在全球范围内严重不足。

抗生素是如此无利可图
,以至于许多大型制药公司

已经停止尝试开发它们。

与此同时
,成功将新抗生素

推向市场的小公司通常仍会破产,
例如美国初创公司 Achaogen。 噬菌体和疫苗等

新的治疗技术

面临与传统抗生素相同的基本问题

如果效果良好,
它们只能使用一次,

因此很难赚钱。

为了长期成功地抵消耐药性

我们需要
谨慎使用新抗生素——


会进一步降低其创造者的利润。

一种可能的解决方案是将利润
从抗生素销售量中转移出去。

例如,英国
正在测试

一种医疗保健提供者
购买抗生素订阅的模式。

尽管政府正在寻找
激励抗生素开发的方法,但

这些计划仍
处于早期阶段。

世界各国
需要做得更多——

但只要
在抗生素开发

和控制使用我们现有药物方面有足够的投资,

我们仍然可以领先于耐药性。