Battling the Antibiotic Apocalypse

Published: November 4, 2025

By Jeremy Martin

12 min read

It started quietly, an invisible invader moving through hospitals, clinics, and homes across the country. In 18 states, patients woke up to blurred vision, their eyes red and swollen. Some felt a stabbing pain, as if shards of glass were etched in their corneas. Others saw nothing at all. By May 2023, 14 people had gone blind, four had lost an eye, and four more were dead.

Months earlier, in February, the Centers for Disease Control and Prevention (CDC) had sounded the alarm: An extremely drug-resistant strain of bacteria—Pseudomonas aeruginosa—was sweeping the nation. Investigators traced the outbreak to an unlikely source: over-the-counter “artificial tears” used by millions to soothe dry eyes. Some bottles had been contaminated with the virulent bacteria, turning a simple remedy into a vector for one of modern medicine’s greatest threats: antimicrobial resistance.

“This strain of Pseudomonas is highly resistant to conventional antibiotics, which makes infections very difficult to treat,” says Michael Zegans, MD, section chief in ophthalmology at Dartmouth Hitchcock Medical Center (DHMC) and professor of surgery, microbiology, and immunology at the Geisel School of Medicine at Dartmouth. “That alone is scary—as is the fact that it led to patient deaths and the need to have some eyes surgically removed.”

While artificial tears leading to lost eyes is newsworthy, outbreaks of drug-resistant bacteria are a far cry from unusual. The World Health Organization (WHO) estimates 1.3 million deaths were directly attributable to antibiotic-resistant pathogens in 2019. In the U.S., antimicrobial resistance (AMR) leads to more than 2.8 million infections and kills 35,000 Americans each year, according to a CDC report. And things are on track to get worse. A meta-analysis published in September 2024 in the medical journal The Lancet projects that by 2050, AMR could claim more lives annually than cancer does today.

“The scariest thing as a clinical laboratory director is a bacterium that causes an infection in a patient and is resistant to every drug we test,” says Isabella Martin, MD, medical director of clinical microbiology at DHMC and assistant professor of pathology and laboratory medicine at Geisel. “It means there are no possible active therapies for their infection.”

Despite the urgent need for stronger medications, antibiotic development takes decades and generates far less profit than drugs for chronic conditions. From 2017 to 2023, only 13 new antibiotics were authorized worldwide, according to a WHO analysis.

This “drug discovery void” leaves patients in the lurch. Yet time is of the essence, Martin says. “Knowing how fast bacteria develop resistance—and how slow we are to develop new agents—can feel like a losing battle sometimes.”

Though the scale of the crisis is daunting, researchers and clinicians at Dartmouth and Dartmouth Health are tackling it head-on. Together, they are uniting science, engineering, and technology to optimize existing treatments, refine diagnostic strategies, and develop alternative therapies. The first step? Understanding what gives superbugs their strength—and how to break those defenses down.

Survival of the Quickest

In 1945, Alexander Fleming won the Nobel Prize in Medicine for discovering penicillin, the world’s first widely used antibiotic. “There is a danger of underdosage,” he warned during his acceptance speech. “It is not difficult to make microbes resistant to penicillin by exposing them to concentrations not sufficient to kill them.”

Fleming’s warning was rooted in a deep understanding of microbiology. Long before humans discovered antibiotics, bacteria were already using these natural chemical weapons to outcompete rivals. In response, other microbes evolved genetic mutations that made them resistant. This microscopic arms race has been unfolding for millions of years, and when we repurpose these molecules for medicine today, resistance is not only possible—it’s inevitable.

As weak bacteria die and resistant ones survive and multiply, once-powerful drugs become the breeders of superbugs. It’s a relentless dance of survival, and the speed of this evolution depends on how we use—or misuse—antibiotics.

As antibiotic resistance threatens to undo a century of medical progress, small actions can still have a big impact. Here’s what you can do to help turn the tide.

Take antibiotics as prescribed. Stopping early can leave resistant bacteria behind.

Don’t pressure your doctor. Antibiotics don’t work for viruses like colds or the flu.

Never share or use leftover antibiotics. Each infection requires the right drug at the right dose and the right time for the right patient.

Prevent infections. Wash hands regularly and clean wounds properly.

Support antibiotic stewardship. If hospitalized, ask about targeted therapies instead of broad-spectrum antibiotics.

Advocate for research. Policies that incentivize new antibiotic development and infection prevention are crucial.

2.8M

Antimicrobial-resistant infections occur in the U.S. each year—contributing to more than 35,000 deaths annually.
2050

The year by which antimicrobial resistance could kill more people annually than cancer does today.
$2.2B

The added cost of antibiotic resistance to the U.S. healthcare system each year, along with over 2 million extra doctor visits.

Eighty years after Fleming’s ominous oration, underdosage is playing out in patients who do not take their antibiotics as directed, leaving bacteria exposed to just enough of the drug to adapt and survive.

But misuse isn’t just about taking too little—it’s also about taking antibiotics when they’re not needed. Antibiotics don’t work against viruses, yet they’re often prescribed for viral infections. The more times broad-spectrum antibiotics are used when a targeted treatment would do, the more the dose becomes the poison.

“Every unnecessary antibiotic is another chance for microbes to evolve and survive,” notes Daniel Schultz, PhD, assistant professor of microbiology and immunology at Geisel. As an expert in dosing dynamics, Schultz studies how the timing and concentration of antibiotics shape bacterial evolution. Using computational models, his lab simulates “real world” infection sites and analyzes how bacteria spread resistance genes throughout the colony.

In 2024, Schultz published novel research on how drug delivery of tetracycline leads to E. coli resistance. His team found that gradual drug exposure frees bacteria to carefully hone their defenses, whereas sudden, high doses trigger more drastic adaptations.

The implications of Schultz’s findings are profound. Antibiotic effectiveness isn’t just about which drug you use—it’s about where, when, how much, and how fast the dose is delivered. For patients, such insights could spell the difference between a treatable infection and a tragic one. For doctors, it could mean making the best of the medicines we have.

The Right Drugs for the Right Bugs

Because bacteria are always evolving, the “right” use of an antibiotic—its selection, dosage, and duration—is constantly in flux over time and across patient populations. A prescribing doctor must not only know the best “bug-drug combinations,” but also regularly update this knowledge and ensure they are properly put into clinical practice.

That’s where antimicrobial stewardship comes in. As of 2017, all U.S. hospitals receiving accreditation by the Joint Commission are mandated to maintain antimicrobial stewardship programs. DHMC is one of the academic medical centers with the oldest stewardship programs, which has grown and evolved since it was established in the 1990s. A leader in the field, DHMC has invested in data-driven strategies to curb antibiotic misuse and combat resistance.

Members of the stewardship team keep a close watch on antibiotic utilization across the hospital, helping care teams “prescribe the right antibiotics to the right patients at the right dose for the right amount of time,” says Rebecca Wang, MD, MED ’16, medical director of antimicrobial stewardship at DHMC and assistant professor of medicine at Geisel.

To help doctors choose the best antibiotics before lab results come back, Wang’s team uses something called a cumulative antibiogram—a yearly report that shows which antibiotics are most likely to work against the bacteria commonly seen at DHMC. Built from test results in Martin’s clinical microbiology lab, the antibiogram gives clinicians a local, up-to-date snapshot of resistance trends. This helps guide treatment decisions when a patient first comes in, even before more specific test results are available.

Once those results do arrive, Wang and her infectious disease pharmacists collaborate with frontline clinicians throughout DHMC to fine-tune treatment plans, again using susceptibility test results from Martin’s clinical laboratory. Sometimes, her team recommends narrower-spectrum antibiotics that she says are “just as effective but carry fewer side effects and contribute less to future antibiotic resistance—not only for the individual patient but also for the institution and [public health] more broadly.”

On the other hand, some cases do require broader coverage. “If a patient is immunocompromised or has a history of infections with resistant organisms, for example, we’ll consult with their oncologists or care providers to consider the nuances and arrive at a treatment decision,” Wang says. “It’s always a dialogue about how to balance the likelihood of effectiveness with stewardship.”

A High-Tolerance Defense

Sometimes, even the right antibiotic fails—not due to resistance, but because some bacteria form “biofilms,” microbial communities whose cellular structures shield against antibiotics and immune cells.

Biofilms grant invading bacteria “more physiological tolerance than genetic resistance and can endure antibiotics at concentrations 10, 100, even 1,000 times higher than free-floating bacteria,” explains George O’Toole, PhD, professor of microbiology at Dartmouth.

Scientist at a microscope — Isabella Martin, MD, director of clinical microbiology at DHMC, examines a microscope slide as part of her work in combating antibiotic resistance. By performing antimicrobial susceptibility tests and overseeing critical diagnostics, she ensures accurate treatment decisions and supports both local and global efforts to slow resistance. Credit: Kata Sasvari

In his lab, O’Toole researches the defenses that make biofilms so hard to treat. His team has zeroed in on specific molecules in the biofilm matrix that trap antibiotics before they reach their target. By disrupting this barrier, O’Toole hopes to revive the potency of treatments that once worked.

Trauma wounds, especially open fractures contaminated with dirt or debris, create an ideal environment for biofilms to form on damaged tissues and surgical hardware, where poor blood flow fetters the immune response and antibiotic delivery.

“In trauma surgery, rates of infection are much higher than in any other field I can think of,” says Leah Gitajn, MD, MS, section chief of orthopaedics at DHMC and associate professor of orthopaedic surgery at Geisel.

In the operating room, Gitajn witnesses how trauma wounds help bacteria to hunker, hide, and thrive—spreading resistance genes. Post-traumatic infection occurs after up to 60% of open bone fractures, and among those treated with antibiotics, infections return more than 30% of the time, Gitajn says. Some infections persist for weeks, months, or even years. For the most virulent strains, treatment options are costly and limited.

“If you can’t cure an infection, patients can suffer severe functional deficits, sometimes even amputation,” Gitajn says. “The consequences of resistance are profound.”

Strength in Numbers

But collaboration is a powerful act of resistance that cuts both ways. And Gitajn has formed her own biofilm of sorts from the evolving colony of researchers and clinicians at DHMC and Geisel.

In 2021, Gitajn, along with Ben Ross, PhD, assistant professor of microbiology and immunology at Geisel, and Carey Nadell, PhD, professor of biological sciences at Dartmouth, received seed funding through a Munck-Pfefferkorn Grant to study microbial communities during infection treatment. Their research aims to enhance treatments for hardware-related infections by using metagenomic sequencing and 3D biofilm imaging to detect and eliminate harmful microbes in trauma wounds and by tracking their evolution during standard therapies.

Together with O’Toole, Ross also researches biofilms in patients with cystic fibrosis (CF), a genetic disease where mucus builds up in the lungs and other organs, causing persistent, and potentially deadly, bacterial infections. Already they’ve found that people with CF who start antibiotics in infancy to treat lung infections tend to develop microbiome defects that thwart the immune system’s ability to ward off future infections.

When it comes to drug resistance, bacteria aren’t the only microbes raising alarms. Fungi are quietly evolving, too, dodging treatments and endangering vulnerable patients. And unlike antibiotics, antifungal options are already limited.

“Fungal infections are increasing. We only have three classes of antifungals, and now we’re seeing resistance to all three,” says Robert Cramer, PhD, professor of microbiology and immunology at Geisel. “It’s not good.”

In Cramer’s crosshairs is the fungus Aspergillus fumigatus, which causes deadly infections when its spores are inhaled. His research highlights a disturbing trend: Agricultural use of azoles, antifungals applied to protect crops, is accelerating resistance in Aspergillus. “Agriculture is flooded with azoles,” he explains. “That’s driving resistance in ways we’re just beginning to understand.”

Like bacteria, fungi have evolved ways to block, evade, or weaken the drugs meant to kill them, rendering treatments less effective and infections harder to fight. Yet antifungals receive little pharmaceutical investment. “Now it’s mostly small biotech and academic labs developing new treatments,” Cramer says.

Fungal infections may not grab headlines like superbugs, but their rising resistance is also a growing crisis. As researchers race for solutions, one thing is clear: We’re in a fight against microbes on all fronts.

“While antibiotics are essential, they may also have unintended consequences that shape long-term health,” Ross says.

As it happens, Pseudomonas aeruginosa—the same pesky germ behind the artificial tears outbreak of 2023—is a major source of chronic lung infections in CF patients.

“P. aeruginosa adapts to the CF lung by forming biofilms that behave like microbial fortresses and make it extremely difficult to eradicate,” Ross says. “If we can identify antibiotics that effectively treat Pseudomonas without disrupting the microbiome as much, we might improve long-term outcomes for CF patients.”

Enter Engineers

Fighting AMR requires solutions that go beyond medicine into fields like engineering, where new technologies can help prevent and combat infections in ways antibiotics alone cannot.

One engineer is shining a light on how biofilms take hold in trauma surgeries. Jonathan Thomas Elliott, PhD, an assistant professor of engineering at Thayer School of Engineering at Dartmouth and of orthopaedics at Geisel, has pioneered a new imaging technique—“fluorescence-guided debridement”—to help surgeons visualize and remove contaminated tissue. Elliott’s technology illuminates areas of poor blood flow and creates a “risk map” so surgeons can see where resistant infections are most likely to occur.

“Right now, surgeons rely on experience and judgment to guide them,” Elliott says. “We’re working on an objective tool to improve decision-making.”

Two scientists at a whiteboard in a lab. — In DHMC’s Pathology and Laboratory Medicine lab, Stewardship Director Rebecca Wang, MD, MED ’16 (left), and Microbiology Lab Director Isabella Martin, MD, work at the intersection of data and diagnostics. Together, they translate lab results into action to stay ahead of antibiotic resistance. Credit: Kata Sasvari

In close collaboration with Gitajn, Elliott’s team has imaged over 200 DHMC patients. But his engineering isn’t just improving prevention efforts. He’s also developing light-activated compounds to destroy bacteria, also known as “photodynamic therapy.” Unlike traditional antibiotics, this method targets multiple bacterial structures simultaneously, preventing resistance from even starting in the first place.

While one engineer harnesses light, another is designing molecules to fight one of medicine’s deadliest microbes. Karl Griswold, PhD, professor of engineering at Thayer School of Engineering at Dartmouth, has been developing ways to attack methicillin-resistant Staphylococcus aureus (commonly known as MRSA), which kills 20,000 Americans annually and has long plagued clinicians and researchers alike.

Conventional antibiotics, which target essential bacterial processes such as protein synthesis or cell wall construction, have traditionally been used against MRSA. But bacteria evolve defenses against these drugs, whether by pumping them out, breaking them down, or changing their own structure so the drugs can no longer latch on—ultimately rendering antibiotics ineffective.

By modifying natural enzymes, however, Griswold and his team have invented a new type of attack that bacteria struggle to resist. One such enzyme, a modified version of lysostaphin called F12, effectively breaks down MRSA’s cell walls and is engineered to evade immune detection.

This “de-immunized” feature solves the problem of previous lysin-based treatments, which triggered immune responses and limited repeated dosing. In lab tests, F12 has demonstrated remarkable efficacy, suggesting it might serve as a reliable new tool in the dwindling arsenal against superbugs.

“Lysins are one of the most promising next-generation antibiotics,” says Griswold. “They kill drug-sensitive and drug-resistant bacteria with equal efficacy, can potentially suppress new resistance phenotypes, and have laser-like precision.”

“Bact” to the Future

Months after the Pseudomonas outbreak, Zegans and other ocular microbiologists published a commentary on the infection with Geisel MD-MBA candidate Frida Velcani. By June 2023, he had co-authored a study on the efficacy of cefiderocol—a drug that slips into bacteria using their own iron transport system—in the treatment of corneal infections with the outbreak strain of Pseudomonas. The group also obtained NIH funding to further their investigations.

It’s one of many examples of how Dartmouth researchers and clinicians are turning crisis into innovation—and how they might just outrun the superbugs. The more Martin advances lab diagnostics, Schultz models dose dynamics, Wang stewards doctors, Ross breaks up biofilms, Griswold engineers enzymes, and Elliott lights up wounds, the more physicians like Gitajn can save patients from losing life or limb—and keep resistance at bay.

The community-wide effort has begun gaining global momentum, too. In September 2024, the United Nations General Assembly gathered in New York, where all countries approved a new political declaration to radically scale up efforts to combat AMR. Today, the WHO now openly acknowledges how AMR could “unwind a century of medical progress” and “return us to the pre-antibiotic era.”

Still, how things will pan out is uncertain. There may be no “right answer,” as Wang puts it, only the reward of a collective effort. “We’re working together to figure out how we can get closest to the right answer for each patient, which might be a different right answer for someone else.”

The superbugs may be evolving, but so are we.

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