A Prescription for Pestilence: The Global Spread of Antimicrobial Resistance

Summary

Antimicrobial resistance isn’t a distant threat — it’s already reshaping medicine. In this episode, we trace how everyday decisions in hospitals, farms, and global health systems have cultivated the rise of drug-resistant microbes. From failed antibiotics to global surveillance gaps, this story reveals how ordinary infections became extraordinary threats — and what it will take to stop the next wave.

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A heartbeat monitor ticks in the background. A ventilator exhales. Hospital footsteps blur into white noise.

A teenage boy comes into the ER with a simple cut on his knee. It’s red, warm, a little swollen. The kind of thing that should clear with a basic antibiotic. A woman has a UTI. She’s had them before. The plan is routine: a short course of medication and she’ll feel better in a day. A newborn develops pneumonia. Fragile, but treatable, because medicine has done this dance thousands of times.

Except this time, it doesn’t go as planned. In the lab, cultures keep growing. One by one, every drug the doctors try fails. The bacteria don’t care about our expectations. They don’t care about our confidence. They don’t care that we thought this stage of history was behind us.

And this isn’t fiction. This is happening in hospitals around the world—right now. Just last week, the UK reported record-high levels of antibiotic-resistant infections: nearly 400 antibiotic-resistant infections every week. Even common UTIs are failing first-line antibiotics at unprecedented rates. We built a world where simple infections were no longer terrifying. Now that world is crumbling.

This is Prescription for Pestilence: The Global Spread of Antimicrobial Resistance

THE MIRACLE THAT CHANGED EVERYTHING

Before we talk about the crisis, we have to remember the miracle.

You've likely heard of Scottish bacteriologist Alexander Fleming in the context of antibiotics, but the story actually begins earlier than Fleming's discovery. In 1910, Paul Ehrlich introduced the world to the first synthetic antimicrobial: an arsenic-based compound called Salvarsan, used to treat syphilis. It was toxic, imperfect, and groundbreaking. Salvarsan opened the modern antimicrobial era—proof that chemistry could be used to target microbes with precision. Over the next decades, antimicrobials of all kinds saved countless lives and drove down diseases that had once defined human suffering.

Then, in 1928, Alexander Fleming walked into his lab and noticed a mold contaminating one of his plates. The bacteria around it were dead. It was the scientific equivalent of stumbling over a matchstick and discovering fire. But it wasn’t just Fleming. Nearly a decade later, Howard Florey, an Australian pathologist, and Ernst Chain, a German-born biochemist, succeeded in isolating and purifying penicillin’s active compound. Their early tests in mice were promising, and in 1941, the drug was used for the first time in humans. One of the first recipients was Albert Alexander, a British policeman with a life-threatening infection from a rosebush scratch. His condition improved but the penicillin ran out and he died. That tragedy catalyzed a global race to produce the drug at scale. By World War II, penicillin was being mass-produced, saving soldiers who, in any other era, would have died from infected wounds. By the end of that war, U.S. pharmaceutical companies were producing over 650 billion units of penicillin every month, transforming medicine forever. In 1945, Fleming, Florey, and Chain shared the Nobel Prize for this breakthrough.

And just as an aside...the US military learned long ago that infection kills more soldiers than bullets. That’s why, no matter what politicians say on camera, you’ll never see the armed forces abandon vaccines or infection control.

Antibiotics didn’t just change medicine—they transformed what it meant to survive. They made surgery safer. They made organ transplants possible. They allowed us to attempt chemotherapy without killing the patient from infection. They made childbirth vastly less deadly. But Fleming wasn’t naïve. In his 1945 Nobel lecture, he warned that the misuse of penicillin could lead to resistant microbes. That if we weren’t careful, the miracle could unravel. And he was right. In fact it was in the 1940s that resistance was detected for the first time. Eighty years later, his warning reads like prophecy.

Now, more than a century after the first synthetic antimicrobial and nearly a century after penicillin, WHO warns in their 2025 report that antibiotic resistance is undermining the very foundation of modern medicine.

But I want to clarify something that can get confusing. Antibiotics are a type of antimicrobial. Antimicrobials include antibiotics, antifungals, antivirals, and antiparasitics.

THE SUPERBUGS AMONG US

Now let’s move this concept of antimicrobial reistance from an abstract idea into something real.

Imagine a patient in a U.S. hospital with a carbapenem-resistant Klebsiella infection. These are not obscure pathogens. They are familiar, everyday bacteria that have learned how to defeat even our most powerful antibiotics. In bloodstream infections, nearly half of all E. coli and over half of all Klebsiella pneumoniae isolates worldwide are now resistant to third-generation cephalosporins, the drugs that were once our dependable first-line therapies. Infections like this can carry mortality rates of 40 to 50 percent. Half a coin flip. Half a family’s world collapsing. According to the latest WHO surveillance data, about one in six bacterial infections worldwide are now resistant to the antibiotics meant to treat them.

Antimicrobial resistance—AMR—is what happens when bacteria evolve to survive the drugs meant to kill them. Sometimes that’s through simple mutations. Sometimes it’s through horizontal gene transfer, where bacteria swap DNA like trading cards.

And this is where the newest science gets even more chilling.

A major Nature study published last week showed that colistin-resistance plasmids—tiny rings of DNA that bacteria can hand off to each other—do more than block one of our last-resort antibiotics. These plasmids also make the bacteria more virulent. The trick lies in changes to surface polysaccharides: the bacterium’s outer coat. These modifications help the microbe evade the immune system while simultaneously neutralizing colistin. Resistance and enhanced pathogenicity in one genetic upgrade.

So when we say bacteria can share resistance genes, we’re not just talking about survival. In some cases, we’re talking about becoming better killers.

Before we go any deeper, I want to share something personal. Back in 2014, long before this podcast existed, I wrote a blog post about antibiotic resistance—why it happens, how it happens, and why so many people misunderstand it. My son had been treated for scarlet fever about a year before that post and instead of watching him suffer horribly with no assurance of his survival, I missed a couple of days of work while he recovered in relative comfort with the help of antibiotics and acetaminophen. And even 11 years ago antibiotic resistance was considered an impending global catastrophe. So, I’ve updated that post for this episode, but the core message is the same: we are all part of the problem, and we all have a role in the solution.

The heart of the problem comes down to two things scientists and physicians have warned us about for decades:

1. We have to use antibiotics with discernment.

2. And when we’re prescribed antibiotics, we have to take every single dose as directed.

Most of us know those rules. Most of us don’t follow them. And many of us don’t really understand why they matter, which makes this whole topic feel abstract—until suddenly it isn’t.

So let’s make it real.

One of the best examples is the infection behind scarlet fever: Streptococcus pyogenes—the bacterium that also causes strep throat, impetigo, some kidney inflammations, and of course some cases of necrotizing fasciitis, the so-called flesh-eating disease. This is a bug with range.

The standard treatment is penicillin, or erythromycin if you’re allergic.

Now imagine you’ve picked up S. pyogenes. Under the right conditions, bacteria can double about every 20 minutes. Scarlet fever has a two-to-three-day incubation period, so by the time you start feeling sick—fever, sore throat, rash—you’ve already built up a large bacterial population in your tissues.

Your doctor prescribes penicillin for ten days, and the bottle helpfully reinforces the instructions: Take all medication as prescribed. Which, translated, means: Take every pill at the right time, you absolute buffoon.

But after 24 hours, the rash fades and you feel dramatically better. After five days, you feel completely fine. So you stop taking the antibiotics and save the leftovers “just in case.”

Here’s what’s actually happening inside your body during those five days.

That big population of bacteria? It’s not uniform. They’re all S. pyogenes, but genetically they’re not identical. Some are extremely susceptible to penicillin. Some are moderately susceptible. A few are more tolerant—not resistant yet, but harder to kill.

When the antibiotic enters your system, the most susceptible bacteria die first. That’s why you feel better so quickly. As long as you keep taking the medicine on schedule, more and more of the bacteria are hit—those that are moderately susceptible, then those that are only somewhat susceptible.

By the time you’re halfway through the prescription, the only bacteria left are the toughest, most tolerant ones. They’re few in number, but they’re the ones that matter.

If you keep taking the antibiotics exactly as prescribed, the drug will continue to accumulate and persist at levels high enough to kill even those most tolerant bacteria.

But if you stop early, those tolerant survivors now have the space, nutrients, and opportunity to reproduce unchecked. All the competitors are gone. The antibiotic pressure is gone. And the bacteria that remain are precisely the ones most capable of developing full resistance.

You might be wondering—if stopping antibiotics early lets the tougher bacteria survive, why don’t people always relapse? The answer is: sometimes they do. Relapses happen when the remaining bacteria regain strength, multiply, and overwhelm the immune system again. But sometimes they don’t, because your immune system finishes the job.

That’s what makes this so tricky. You might feel fine. You might even stay fine. But those tougher, more tolerant bacteria are still in your body—or in your household, or your community. And even if you don’t get sick again, you can still pass those hardier microbes on to someone else.

So the danger isn’t just relapse. It’s resistance spreading quietly, person to person, even when no one feels sick. And the next time those bacteria cause an infection—in you or in someone else—they may no longer respond to treatment.

This is how antibiotic resistance emerges not just in hospitals or farms or wastewater systems—but inside us. Inside our families. Inside our communities.

Antibiotics don’t magically clear an infection because they “worked.” They work because you take them long enough and consistently enough to kill all the bacteria—including the ones that are hardest to kill. Quit early, and you create the perfect training ground for the strongest survivors.

And when we repeat this pattern across millions of people and millions of prescriptions, we create the conditions that bring us closer to a true post-antibiotic era.

An era when infections that used to be routine—strep throat, UTIs, skin infections—become serious again. When surgeries become riskier. When treating gonorrhea requires IV therapy. When amputations become a last-ditch lifesaving measure, not a historical relic.

People sometimes assume scientists will just “make new antibiotics” the way we discovered the first ones. But the early breakthroughs were rare strokes of luck; the low-hanging fruit has already been picked. Creating new, safe, effective antibiotics is slow, expensive, and scientifically difficult. And progress has stalled.

Which is why preserving the antibiotics we already have is not just good practice. It’s survival strategy.

Get diagnosed properly. Don’t demand antibiotics for viral infections. Ask for tests. Clarify uncertainties. And when antibiotics truly are needed—take them exactly as prescribed. Finish the course. Don’t save extras. Don’t share them.

Every responsible choice protects not just you, but everyone around you.

Because the post-antibiotic era isn’t a future we want to stumble into. And as individuals, we have more power than we think to delay it.

THE GLOBAL CRISIS

Zoom out.

Take that microscopic survival contest—the toughest bacteria winning inside a single infection—and now multiply it by billions of infections every year, across billions of bodies. That’s the global antimicrobial resistance crisis we’re living through right now.

WHO’s 2025 data show carbapenem resistance rising five to fifteen percent every year in major pathogens like E. coli, Klebsiella, Acinetobacter, and non-typhoidal Salmonella. And in the UK, the newest surveillance report echoes the pattern: more carbapenemase-producing Enterobacterales, more treatment-resistant UTIs, more resistant bloodstream infections, more drug-resistant gonorrhea. Maps that once showed isolated clusters now look like a spreading stain.

Beyond Bacteria — The Wider AMR Landscape

We tend to think of AMR as a bacterial story. But resistance crosses kingdoms.

Antimicrobial resistance also includes fungi, viruses, and parasites, each with its own rules of evolution and its own dangers.

Fungal Resistance: A Rising, Under-the-Radar Threat

In ICUs around the world, drug-resistant yeasts are becoming some of the most dangerous pathogens we face. One of the most concerning: Candidozyma auris—formerly Candida auris.

In 2025, the UK Health Security Agency formally adopted the new name to reflect its distinct genetic lineage. But most clinicians still call it C. auris, and we will too—for clarity.

This yeast can persist on surfaces, resist standard disinfectants, and slip past routine diagnostics. Outbreaks are notoriously hard to control. Mortality rates in immunocompromised patients often exceed 30–60 percent, especially when the strain is resistant to fluconazole or even echinocandins—the drugs that are supposed to be our last line of defense.

Viral Resistance: The Hidden Half of AMR

Viruses evolve under pressure too.

HIV remains the clearest example: drug-resistant strains—especially to non-nucleoside reverse transcriptase inhibitors (NNRTIs)—still complicate treatment in many regions of the world. Influenza, meanwhile, mutates fast enough that seasonal strains periodically develop resistance to oseltamivir, the antiviral better known as Tamiflu.

These examples remind us that AMR isn’t just a bacterial arms race. It’s a biological arms race—everywhere.

Back to the Global Picture

WHO reports rising fluoroquinolone resistance in foodborne pathogens like non-typhoidal Salmonella and Shigella, making everyday gastrointestinal infections harder to treat across entire regions. And gonorrhea? Fluoroquinolone resistance is now nearly universal—around 75 percent globally—and while ceftriaxone still works, early resistance signals are emerging.

Resistance doesn’t respect hospital walls—or borders.

Worldwide, AMR contributes to roughly five million deaths every year—that’s more than HIV, malaria, or even some forms of cancer. And yet, it receives a fraction of the attention and funding. But the burden is uneven. In South-East Asia, nearly one in three bacterial infections are resistant. In Europe, it’s closer to one in ten.

More than half the countries reporting to WHO still lack core diagnostic and surveillance capability. Most resistance is happening in the dark.That’s why WHO calls this a syndemic—resistance layered onto fragile health systems, magnifying harm.

And even in wealthy nations, resistance continues to accelerate. The latest UK data make that painfully clear.

THE ONE HEALTH REALITY

The drivers of AMR don’t stop at human medicine, so let's look at the One Health implications. Agriculture uses more antibiotics by volume than healthcare does—given for growth promotion, prophylaxis, and to compensate for overcrowded conditions.

And antibiotics don’t just disappear after we use them. They enter wastewater systems through hospitals, homes, and farms—ending up in rivers, soil, and sediments. There, they create environmental “resistance hotspots,” where bacteria share resistance genes freely. This environmental resistome—a genetic reservoir of resistance traits—can spill over into pathogens that infect humans and animals. It’s a microbial ecosystem we’re only beginning to understand, but it’s already shaping the future of resistance.

This is the One Health landscape: humans, animals, ecosystems—interconnected, influencing one another, sharing the same microbial battleground.

And every November, World AMR Awareness Week reminds us: Preventing antimicrobial resistance together isn’t just a theme. It’s the only way forward.

FIGHTING BACK: INNOVATION AND STEWARDSHIP

Here’s the good news: we’re not helpless. Antibiotic stewardship is the practice of using these drugs carefully—choosing the right drug, at the right dose, for the right duration. It means ordering the right tests. It means not treating every fever with a broad-spectrum antibiotic “just in case.”

Closing the Diagnostic Gap

One of the most overlooked drivers of antibiotic misuse isn’t overconfidence—it’s uncertainty. When a patient shows up with a fever, a cough, or abdominal pain, doctors often face intense pressure to act quickly. And when the right tests aren't available— or take too long—empirical antibiotic use becomes the default. “Just in case” becomes policy.

The result? Millions of antibiotic prescriptions are written every year with no confirmed diagnosis, especially in settings where lab infrastructure is weak. But the truth is, diagnostic gaps exist in wealthy countries too. Even in major hospitals, cultures can take days. And many outpatient clinics have no access to bacterial testing at all.

This is where rapid diagnostics can change the game. Tools like multiplex PCR panels can detect dozens of pathogens from a single swab in hours instead of days. MALDI-TOF mass spectrometry—a form of bacterial fingerprinting—can identify species within minutes once a culture grows. And point-of-care CRP or procalcitonin tests can help determine whether an infection is likely bacterial or viral, reducing unnecessary antibiotic use for things like viral bronchitis.

Studies have shown that when clinicians have access to rapid diagnostics, they prescribe more accurately—and more conservatively. Because precision medicine isn’t just for cancer care. It’s a core tool in antimicrobial stewardship.

But access remains deeply unequal. According to WHO’s latest report, more than half of countries still lack routine lab-based surveillance for AMR, and many can’t confirm resistance patterns locally. That means resistance often spreads unseen—until it’s too late.

Strengthening diagnostic infrastructure isn’t just about detecting outbreaks. It’s about making sure that every prescription is backed by evidence, not guesswork.

But WHO’s 2025 surveillance shows that we’re still relying too heavily on broad-spectrum ‘Watch’ antibiotics. The WHO classifies antibiotics into three groups: Access, Watch, and Reserve. Access antibiotics are narrow-spectrum, first-line drugs—safer for routine use and less likely to drive resistance. Watch antibiotics are broader, more powerful, and more likely to breed resistance if overused. Reserve antibiotics are last-resort treatments, held back for the most severe, drug-resistant infections when nothing else works. Yet Access antibiotics—the ones we should be relying on most—make up only about fifty-three percent of global use, far below the seventy percent target set for 2030. And this matters, because using powerful Watch antibiotics as routine tools is like burning through your emergency supplies just to get through the week. These drugs select for resistance more aggressively. So every time they’re used when a simpler drug would have worked, we shorten the lifespan of the few antibiotics we have left.

Innovation in the Pipeline

And while the pipeline is still too thin, there are bright spots. Cefiderocol, a siderophore cephalosporin, is one of the few new antibiotics active against carbapenem-resistant Acinetobacter and Enterobacterales—some of the toughest superbugs we face. Bacteriophage therapy—viruses that hunt bacteria—is also making a comeback, with personalized bacteriophage treatments successfully saving patients with infections resistant to every available antibiotic.

A Life Saved by Phages

One of the most powerful reminders of what’s at stake—and what’s possible—comes from Dr. Steffanie Strathdee, an infectious disease epidemiologist at UC San Diego. In 2016, her husband was dying from a multidrug-resistant infection. Every antibiotic had failed.

But Strathdee refused to accept that this was the end. She and a global team of scientists turned to phage therapy—using viruses that infect and kill bacteria. Working with researchers from UCSD’s Center for Innovative Phage Applications and Therapeutics, the U.S. Navy, and international collaborators, they found a combination of bacteriophages that worked. Her husband survived.

My copy of the Perfect Predator on a fake fur blanket because I was reading it in the winter. LOL Great read, though! Seriously!

The case helped reignite global interest in phage therapy, and Strathdee and her husband went on to co-author their memoir, The Perfect Predator, which documents their race against time. For her efforts, she was named one of TIME’s 50 Most Influential People in Health Care.

Their story is more than a medical miracle—it’s a reminder that innovation often starts with desperation, collaboration, and the refusal to give up. And in the fight against superbugs, we’ll need all three.

Beyond killing bacteria, researchers are exploring non-traditional strategies—like anti-virulence compounds that disarm pathogens rather than destroy them, and immune enhancers that help the body clear infections more effectively. These approaches won’t replace antibiotics overnight, but they offer a glimpse of what a more resilient future might look like. AI-driven drug discovery is accelerating the search for new antimicrobials. Microbiome-protective therapies aim to disarm resistance rather than kill bacteria outright. But WHO warns that the global antibiotic pipeline remains too thin to counter rising resistance in critical pathogens like carbapenem-resistant Acinetobacter and Enterobacterales.

But it’s hard. Antibiotics are uniquely difficult to develop. Drug companies don’t want to invest billions in a medication that doctors intentionally try not to use. Short courses mean low profits. Stewardship, ironically, makes success financially punishing.

And the need is urgent. Because papers like the new Nature study don’t just warn us—they show us that bacteria are evolving faster, smarter, and with more sophisticated virulence strategies than we once believed.

Policy efforts like the U.S. PASTEUR Act (the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance Act), CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), and BARDA funding (the Biomedical Advanced Research and Development Authority) aim to bridge the economic gap. But they need support, political will, and public pressure.

And at the individual level, we can still make a difference: Don’t demand antibiotics for viral infections. Finish prescriptions. Never share leftover meds.

Vaccines — The Unsung AMR Defense

And vaccinate—because every infection prevented is an antibiotic we didn’t have to use. We don’t usually think of vaccines as part of the fight against antimicrobial resistance. But they are—quietly, effectively, and at scale.

Vaccines don’t just protect individuals from disease. They also reduce the number of infections that would otherwise require antibiotics in the first place. Every case of pneumonia, typhoid, or otitis media prevented is one less antibiotic course, one less opportunity for resistance to emerge.

Take the pneumococcal conjugate vaccine, or PCV. Since its rollout, countries around the world have seen sharp declines in infections caused by resistant strains of Streptococcus pneumoniae. The vaccine targets specific serotypes—many of which were also the most drug-resistant. When those serotypes disappear, the burden of resistant disease drops with them.

Or look at typhoid fever in South Asia. In 2019, Pakistan became the first country to introduce the typhoid conjugate vaccine into its routine immunization program in response to a large outbreak of extensively drug-resistant (XDR) Salmonella Typhi—strains that resist nearly every oral antibiotic. Since then, case rates and resistant infections have fallen sharply in vaccinated districts.

The same principle applies to influenza, rotavirus, Haemophilus influenzae type B, and even COVID-19: by preventing severe disease and the complications that follow—including secondary bacterial infections—vaccines help reduce the need for antibiotics.

And in low-resource settings, where access to diagnostics is limited and antibiotics are often overused as a default, vaccines offer an especially powerful way to slow resistance before it starts.

Every dose we save today buys time for tomorrow’s patients.

THE HUMAN STORY

And behind each of the statistics around antimicrobial resistance, are millions of families affected every year—because resistance isn’t abstract. WHO’s data reflect real people whose infections no longer respond to the drugs they should.

For urinary tract infections—the most common bacterial infections—WHO reports that resistance to several first-line antibiotics now exceeds 30 percent globally. In the UK this year, clinicians described a toddler with a drug-resistant UTI who cycled through three antibiotics before finally improving. The IV medication that saved them was once reserved for only the most severe infections. Now it’s being used more and more often.

Or consider a parent watching their child deteriorate while doctors try drug after drug, hoping one will work. Or a nurse who has spent a career watching infections that used to be easy—routine—become frightening again.

These stories aren’t dramatic because they’re rare. They’re dramatic because they’re becoming common.

And I think about my own training in virology, how modern medicine is built on the foundation that infections are manageable. That antibiotics will be there. That progress only moves forward.

We are not powerless. But we are on borrowed time.

THE END OF THE MIRACLE?

When penicillin was discovered, it rewrote the rules of life and death. But miracles don’t sustain themselves. They have to be protected.

The WHO 2025 report makes one thing clear: resistance is accelerating, and without global action, the antibiotics that reshaped modern medicine may not protect us for much longer. The newest UK surveillance data shows resistance rising. The newest science shows plasmids that make bacteria stronger and deadlier. But none of this is destiny. It’s a warning—and a call.

The age of antibiotics gave us power over disease. But power without stewardship becomes a liability. Protect it—or lose it.

World Antimicrobial Resistance Awareness Week is November 18–24. Learn. Share. Act. Let’s all practice antimicrobial stewardship so we don’t hand tomorrow’s patients a crisis we could have prevented.

I appreciate you being here for this story—it matters. And next week, we’ll shift gears for our second Outbreak After Dark episode of the season, diving into a Thanksgiving special on Pilgrims and Plagues.