He was their ‘little miracle.’ What happens when antibiotics stop working

Dr. Felix Liauw remembers the first time he held his son, Obelix.

“He looked perfect. He was our little miracle,” the pediatrician, 40, told CNN.

After seven years of trying to conceive, Liauw and his wife were overjoyed to welcome their firstborn. But their happiness was soon overshadowed when his tiny body rejected food, with vomiting and diarrhea after every bottle, up to eight times a day.

Early on, Liauw’s wife adjusted her diet, suspecting a breast milk allergy.

But symptoms persisted, and Obelix was put into neonatal intensive care and rehydrated at just 2 weeks old.

“He just kept crying, crying, crying, all day long,” Liauw said from his home in Bekasi city, Indonesia.

“If we didn’t feed him, he was OK, but he was so hungry all the time.”

Liauw consulted a pediatric nutritionist who suggested a special milk formula for Obelix, but this didn’t help, and his weight dropped from 2.4 kilograms (about 5 pounds) to 2.2 kg.

At 1 month old, he was given a feeding tube and diagnosed with a bowel infection at a hospital in Jakarta. Doctors prescribed different types of antibiotics, hoping to find one that would work, but to no avail.

Blood tests later pointed to congenital short bowel syndrome, a rare disorder that prevented Obelix from digesting food and led to prolonged hospital care.

Still tiny, Obelix developed sepsis, an extreme reaction to infection.

Blood tests showed that none of the antibiotics doctors had hoped would tame the infection were working, and Obelix died in hospital on February 12, 2020. He was just 3 months and 2 weeks old.

No autopsy was conducted, but the series of events convinced his parents that antimicrobial resistance – or AMR – had played a role in his death.

AMR is one of the global health challenges of the 21st century. According to the World Health Organization (WHO), it happens when bacteria – as well as viruses, fungi and parasites – change in ways that make the drugs used to treat them no longer effective.

Although this process happens naturally, it’s been a known threat for a long time. About 100 years ago, Oxford researchers observed bacteria that could destroy penicillin, even before the drug was widely used.

By the 1980s, doctors were seeing multidrug-resistant strains spreading globally. Since then, awareness and efforts to combat AMR have increased – but so has the threat.

In 2021 – a year after little Obelix’s death – the phenomenon was linked to 4.7 million deaths worldwide. By 2050, WHO estimates, that number could rise to as many as 39 million annually, and eventually affect everyone.

One of the main drivers of resistance is the overuse of antibiotics, both in people and in farming, which can speed up the emergence of drug-resistant “superbugs.”

That’s why WHO warns against self-medicating with antibiotics and urges people to always finish any prescribed course.

Still, in the five years to 2023, the WHO found that more than 40% of antibiotics had lost their effectiveness against routine illnesses like urinary tract and sexually transmitted infections.

“These findings are deeply concerning,” said Dr. Yvan Hutin, head of WHO’s AMR department. “As antibiotic resistance continues to rise, we’re running out of treatment options, and we’re putting lives at risk.”

Despite growing awareness, global antibiotic consumption is rising. And it’s not just people who are taking them when they’re ill; Large volumes of antibiotics are used in agriculture, typically to promote growth in poultry and livestock – a practice seen worldwide, far beyond Liauw’s home in Indonesia.

The European Union has taken action, banning antibiotics as growth agents for farm animals in Europe and will extend this rule to all livestock imports in September.

However, the US still allows antibiotics for growth promotion, and reported a 16% rise in the sale and distribution of antimicrobials for food-producing animals between 2023 and 2024, according to the most recent figures. Some of that was due to the outbreak of Avian metapneumovirus in turkeys and chickens and bird flu, according to the US Food and Drug Administration (FDA).

Mallory Smith died in Los Angeles at age 25 from an infection that antibiotics could not beat.

Diagnosed at age 3 with cystic fibrosis, a genetic disease that clogs the lungs with sticky mucus, Smith grew up with doctors expecting a cure to arrive in time to save her.

But as she approached her teenage years, her lungs became infected with B. cepacia, a dangerous bacteria that resists most antibiotics.

The infection led to nearly 70 hospitalizations.

By 2016, antibiotics had failed. Smith had a double lung transplant, but her infection lingered, and she died two months later in November 2017.

“Antibiotics couldn’t resolve the infection,” her mother, Diane Shader Smith, told CNN.

“It’s like a fire you thought you put out, but the embers still remain, and the flames come back hotter, faster and harder to control.”

Before Smith’s death, doctors had secured approval from the FDA to give her bacteriophage therapy, an experimental therapy available in the US only through emergency compassionate use or one-off requests as an investigational new drug.

Discovered over a century ago, bacteriophages use viruses – created by nature – to attack “superbugs.”

However, finding the right phage to target a patient’s infection is an enormous challenge; so many phages exist that scientists estimate there’s a trillion for every drop of water or grain of sand.

So far, the use of phages to treat bacterial infections is limited to a handful of countries, and some see them as a potential solution to the growing problem of antibiotic resistance.

Although phage therapy did not save Smith’s life, an autopsy confirmed that it had begun to work, her mother said.

Throughout her life, Smith documented her journey in diary entries, often describing the solace she found at sea, where salt water soothed her scarred lungs and surfing calmed her mind.

“Losing Mallory was a catastrophic event in my life, but raising awareness has propelled me forward,” Shader Smith said.

Since her daughter’s death, Shader Smith has traveled the world, raising awareness about AMR and about the potential of phage therapy to save lives.

WHO says phage therapy is generally safe, as phages don’t target human cells, but more testing is needed before their use becomes more widespread.

The medical treatment isn’t a universal fix for all bacterial infections. Like antibiotics, phages can cause the release of endotoxins, or toxic substances, which can cause a severe inflammatory – and potentially fatal – response, like septic shock.

Unlike Smith’s story in Los Angeles, AMR tends to hit hardest in lower-income countries – in Southeast Asia where Liauw lives, as well as South Asia and sub-Saharan Africa – according to the US National Institutes of Health.

But these resistant bugs circulate worldwide, “affecting healthcare systems across all income levels,” Dr. Xin Deng, professor of biomedical sciences at the City University of Hong Kong, told CNN.

What separates countries is not the germs themselves but the resources available to tackle them, Deng added.

Other factors include a country’s ability to prevent infections, diagnose accurately, control environmental contamination and enforce regulations, Deng said.

For some, even treating cuts and wounds could become problematic if AMR spreads due to the risk of a runaway infection.

“Some bacteria inherently pose higher AMR risks,” said Deng, who has studied the topic for 15 years.

One example is a bacterium called Pseudomonas aeruginosa, he said, which is linked to infections like meningitis, pneumonia and septicemia – a major risk to people with cystic fibrosis, like Smith.

Along with smarter antibiotic use, Deng called for more public education, healthcare training, vaccination programs and investment for research and diagnostic tools.

“The harsh reality is that with each year of inaction, the AMR crisis will only become more dangerous, more costly to address and significantly more difficult to control,” he said.

By 2050, AMR could cost the world $1.7 trillion in annual GDP losses, research suggests.

Momentum to address antimicrobial resistance is building, with more than 170 countries developing action plans and WHO member states agreeing last year to an updated strategy to reduce AMR-related deaths by 10% by 2030.

The new plan seeks to slash the quantity of antimicrobials used in the world’s agri-food systems and improve sanitation and hygiene. It also calls for better lab tests and improved surveillance – steps that could help in cases like Obelix’s.

For Liauw, it’s a cause he continues to champion in honor of his child.

“We shouldn’t always diagnose infections only based on certain symptoms. We have to take a more holistic approach, like with my son,” Liauw said.

“His case is not a common one, but it shows the risk of AMR can be deadly.”

CNN’s Meera Senthilingam contributed to this report.

费利克斯·廖医生还记得他第一次抱起儿子奥贝利克斯的情景。

“他看起来完美无瑕。他是我们的小奇迹，”这位40岁的儿科医生告诉CNN。

经过七年的备孕，廖和妻子欣喜若狂地迎来了他们的第一个孩子。然而，这份喜悦很快就被孩子的小小身体所掩盖，孩子每次喝完奶瓶后都会呕吐和腹泻，一天多达八次。

很早以前，廖的妻子就调整了自己的饮食，怀疑自己对母乳过敏。

但症状持续存在，奥贝利克斯出生仅 2 周就被送入新生儿重症监护室接受补液治疗。

“他整天都在哭，哭，哭，”廖在印度尼西亚勿加泗市的家中说道。

“如果我们不喂他，他也没事，但他总是很饿。”

廖咨询了一位儿科营养师，营养师建议给奥贝利克斯喝一种特殊的奶粉，但这并没有帮助，他的体重从 2.4 公斤（约 5 磅）下降到 2.2 公斤。

他一个月大的时候，在雅加达一家医院被诊断出肠道感染，并被插上了喂食管。医生们开了不同类型的抗生素，希望能找到一种有效的，但都无济于事。

血液检查结果显示，奥贝利克斯患有先天性短肠综合征，这是一种罕见的疾病，导致他无法消化食物，并需要长期住院治疗。

奥贝利克斯年纪还小，却患上了败血症，这是对感染的一种极端反应。

血液检测结果显示，医生们希望用来控制感染的抗生素均无效，奥贝利克斯于 2020 年 2 月 12 日在医院去世，年仅 3 个月零 2 周。

虽然没有进行尸检，但这一系列事件让他的父母确信抗菌素耐药性（或称 AMR）在他的死亡中起了作用。

抗菌药物耐药性是21世纪全球面临的健康挑战之一。世界卫生组织（世卫组织）指出，当细菌（以及病毒、真菌和寄生虫）发生变异，导致用于治疗它们的药物不再有效时，就会发生抗菌药物耐药性。

虽然这个过程是自然发生的，但它长期以来一直是一个已知的威胁。大约100年前，牛津大学的研究人员就观察到一些细菌能够破坏青霉素，甚至在青霉素被广泛使用之前就发现了这种细菌。

到了20世纪80年代，医生们发现多重耐药菌株在全球范围内蔓延。自那时起，人们对抗菌素耐药性的认识和应对措施都有所提高，但威胁也随之加剧。

2021年，也就是小奥贝利克斯去世一年后，这种现象导致全球470万人死亡。世界卫生组织估计，到2050年，这一数字可能上升到每年3900万人，最终影响到所有人。

抗生素耐药性的主要驱动因素之一是人类和农业中抗生素的过度使用，这会加速耐药性“超级细菌”的出现。

因此，世界卫生组织警告不要自行服用抗生素，并敦促人们务必完成所有处方疗程。

不过，世界卫生组织发现，在截至 2023 年的五年间，超过 40% 的抗生素对尿路感染和性传播感染等常见疾病失去了疗效。

世卫组织抗菌素耐药性部门负责人伊万·胡廷博士表示：“这些发现令人深感担忧。随着抗生素耐药性的持续上升，我们的治疗选择越来越少，我们正在将生命置于危险之中。”

尽管人们的意识日益增强，但全球抗生素消耗量仍在上升。而且，服用抗生素的不仅仅是生病的人；农业中也大量使用抗生素，通常是为了促进家禽和牲畜的生长——这种做法在世界各地都很普遍，远远超出了廖的家乡印度尼西亚。

欧盟已采取行动，禁止在欧洲农场动物中使用抗生素作为生长剂，并将于 9 月把这项规定扩展到所有牲畜进口。

然而，美国仍然允许使用抗生素促进动物生长。根据最新数据，2023年至2024年间，用于食用动物的抗菌药物的销售和分销量增长了16%。美国食品药品监督管理局（FDA）指出，部分原因是由于火鸡和鸡爆发禽偏肺病毒和禽流感疫情。

马洛里·史密斯在洛杉矶去世，年仅 25 岁，死于一种抗生素无法治愈的感染。

史密斯在 3 岁时被诊断出患有囊性纤维化，这是一种遗传性疾病，会导致肺部充满粘稠的粘液。医生们一直期待着能及时找到治愈方法来挽救她的生命。

但随着她接近青少年时期，她的肺部感染了洋葱伯克霍尔德菌，这是一种对大多数抗生素具有抵抗力的危险细菌。

这次感染导致近70人住院。

到2016年，抗生素治疗已经无效。史密斯接受了双肺移植手术，但感染持续存在，两个月后，她于2017年11月去世。

“抗生素无法治愈感染，”她的母亲黛安·谢德·史密斯告诉 CNN。

“这就像你以为已经扑灭了一场火，但余烬仍然存在，火焰会更猛烈、更快、更难控制地卷土重来。”

在史密斯去世之前，医生们已经获得了美国食品药品监督管理局 (FDA) 的批准，可以给她进行噬菌体疗法。噬菌体疗法是​​一种实验性疗法，在美国只能通过紧急同情用药或作为研究性新药的一次性申请才能获得。

噬菌体在一个多世纪前被发现，它利用自然界产生的病毒来攻击“超级细菌”。

然而，找到合适的噬菌体来治疗患者的感染是一项巨大的挑战；噬菌体的数量如此之多，以至于科学家估计，每一滴水或每一粒沙子中都含有数万亿个噬菌体。

目前，噬菌体在治疗细菌感染方面的应用仅限于少数几个国家，一些人认为噬菌体是解决日益严重的抗生素耐药性问题的潜在方案。

史密斯的母亲说，虽然噬菌体疗法没能挽救史密斯的生命，但尸检证实该疗法已经开始起效。

在她的一生中，史密斯一直用日记记录着她的旅程，经常描述她在大海中找到的慰藉，海水抚慰了她伤痕累累的肺部，冲浪使她的心灵平静下来。

“失去马洛里是我人生中的一场灾难，但提高公众意识让我继续前进，”谢德·史密斯说。

自女儿去世后，谢德·史密斯周游世界，提高人们对抗菌素耐药性以及噬菌体疗法拯救生命的潜力的认识。

世界卫生组织表示，噬菌体疗法总体上是安全的，因为噬菌体不会攻击人类细胞，但在更广泛地使用之前，还需要进行更多测试。

这种药物治疗并非对所有细菌感染都有效。与抗生素一样，噬菌体也会导致内毒素（一种有毒物质）的释放，从而引发严重的炎症反应，甚至可能致命，例如败血性休克。

与史密斯在洛杉矶的故事不同，根据美国国立卫生研究院的说法，抗菌药物耐药性往往对低收入国家造成最严重的打击——在廖居住的东南亚，以及南亚和撒哈拉以南非洲。

但香港城市大学生物医学科学教授邓欣博士告诉 CNN，这些耐药菌在世界各地传播，“影响着各个收入阶层的医疗保健系统”。

邓补充说，真正区分各国的不是病菌本身，而是应对病菌的资源。

邓表示，其他因素包括一个国家预防传染病、准确诊断、控制环境污染和执行法规的能力。

对于某些人来说，如果抗菌素耐药性蔓延，由于存在感染失控的风险，即使是治疗割伤和伤口也可能变得很困难。

“有些细菌本身就具有更高的抗菌素耐药性风险，”邓教授说道，他研究这个课题已有15年之久。

他举例说，铜绿假单胞菌就是一个例子，它与脑膜炎、肺炎和败血症等感染有关——这对像史密斯这样的囊性纤维化患者来说是一个重大风险。

邓小平除了呼吁更合理地使用抗生素外，还呼吁加强公众教育、医疗培训、疫苗接种计划，并加大对研究和诊断工具的投资。

“残酷的现实是，每拖延一年，抗菌素耐药性危机只会变得更加危险，应对成本更高，控制难度也更大，”他说。

研究表明，到 2050 年，抗菌药物耐药性可能导致全球每年 GDP 损失 1.7 万亿美元。

应对抗菌素耐药性的势头正在增强，已有 170 多个国家制定了行动计划，世界卫生组织成员国去年也同意了一项更新的战略，目标是到 2030 年将与抗菌素耐药性相关的死亡人数减少 10%。

新计划旨在大幅减少全球农业食品系统中抗菌药物的使用量，并改善卫生条件。该计划还呼吁改进实验室检测方法和加强监测——这些措施或许有助于解决像奥贝利克斯这样的案例。

对于廖来说，这是他为了纪念自己的孩子而继续支持的一项事业。

“我们不应该总是只根据某些症状来诊断感染。我们必须采取更全面的方法，就像对待我儿子那样，”廖说。

“他的病例虽然不常见，但表明抗菌药物耐药性的风险可能是致命的。”

CNN的米拉·森蒂林加姆对本报道亦有贡献。