Antimicrobial Resistance: A Growing Threat to Modern Medicine

For nearly a century, antibiotics have served as the foundation of modern healthcare. The discovery of penicillin by Alexander Fleming transformed once-fatal infections into treatable conditions and enabled advances ranging from complex surgeries and cancer chemotherapy to organ transplantation and neonatal intensive care. Today, however, that foundation is under increasing strain. Antimicrobial resistance (AMR) is reducing the effectiveness of many of the antibiotics upon which healthcare systems depend. Pathogens such as carbapenem-resistant Enterobacterales (CRE), multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii continue to spread globally, causing infections that are increasingly difficult and costly to treat. In 2021, it was estimated that 4.71 million deaths were associated with bacterial AMR, including 1.14 million deaths directly attributable to bacterial AMR. Without a steady supply of new antibacterial agents, the medical community risks losing ground in the fight against infectious diseases and jeopardizing many of the advances that define modern medicine.

The antibiotic innovation crisis

While the need for new antibiotics has never been greater, the antibiotic marketplace has become one of the most challenging sectors in the pharmaceutical industry. Unlike therapies used to treat chronic conditions, antibiotics are typically prescribed for only a few days and, in the case of new agents, are often reserved as last-line treatments to preserve their effectiveness. This stewardship-driven approach is clinically appropriate but economically unsustainable. Developing a novel antibiotic requires hundreds of millions of dollars and more than a decade of research, yet sales often fail to support continued investment. As a result, many large pharmaceutical companies have abandoned antibacterial research altogether, while several smaller biotechnology companies that successfully developed and commercialized innovative antibiotics ultimately failed financially. The outcome is a global innovation gap at precisely the moment when resistant infections are becoming more prevalent and more dangerous.

Why pull incentives matter

The growing recognition that antibiotics are a societal necessity rather than a conventional commercial product has prompted governments to explore new approaches to support innovation. Over the past several years, policymakers have increasingly embraced “pull incentives” — economic models that reward the availability and public health value of an antibiotic rather than the number of prescriptions written. The United Kingdom has pioneered this approach through its subscription-based reimbursement program, while similar initiatives are being developed throughout Europe and North America. In the United States, the proposed PASTEUR Act has garnered broad support and could provide contracts ranging from US$250 million to US$500 million per year for critically important antibiotics. Combined with investments from international organizations and AMR-focused funding initiatives, governments have already committed several billion dollars toward rebuilding the antibiotic ecosystem, with many experts estimating that tens of billions more will be required globally. These investments are increasingly viewed as essential national healthcare infrastructure, ensuring that effective antibiotics remain available when they are needed most.

The scientific team behind some of the most important advances in resistance

Fedora Pharmaceuticals was founded by a team whose contributions have helped shape the modern treatment of resistant bacterial infections. The company's scientific leadership includes key innovators behind tazobactam, one of the most successful and widely used β-lactamase inhibitors ever developed. For more than three decades, tazobactam has played a critical role in restoring the effectiveness of β-lactam antibiotics against resistant pathogens and remains a cornerstone of antibacterial therapy worldwide. Building upon this legacy, the Fedora team subsequently pioneered nacubactam, a next-generation β-lactam enhancer that combines potent β-lactamase inhibition with direct antibacterial activity through penicillin-binding protein binding. Nacubactam introduced a novel mechanism designed to address some of the most challenging resistance mechanisms emerging in Gram-negative pathogens and further established Fedora's reputation as a leader in resistance-breaking technologies.

FPI-2119: addressing the world's highest-priority resistant pathogens

Today, Fedora is advancing FPI-2119, a first-in-class, non-β-lactam penicillin-binding protein inhibitor derived from the lactivicin family of natural products. Remarkably, despite decades of scientific interest in the lactivicin class, no compound from this class has previously reached clinical development. FPI-2119 represents an entirely new approach to targeting bacterial cell-wall synthesis and has demonstrated potent activity against many of the pathogens identified as critical threats by the World Health Organization, the U.S. Centers for Disease Control and Prevention, and Canadian public health agencies. These include multidrug-resistant Escherichia coli, Klebsiella pneumoniae, Enterobacter species, carbapenem-resistant Enterobacterales, and difficult-to-treat Pseudomonas aeruginosa. Importantly, FPI-2119 has shown activity against strains carrying resistance mechanisms that compromise many currently available therapies, including organisms that continue to challenge hospitals around the world.

Continuing a legacy of innovation

Throughout the history of antibiotic development, only a small number of scientific teams have successfully delivered truly transformative advances against antimicrobial resistance. From the development of tazobactam, to the invention of nacubactam, to the advancement of the first candidate from the lactivicin class, Fedora Pharmaceuticals has consistently focused on solving the most difficult problems in infectious diseases. At a time when the world urgently needs new solutions to combat antimicrobial resistance, Fedora remains committed to discovering and developing the next generation of antibacterial medicines capable of protecting patients, strengthening healthcare systems, and preserving the effectiveness of antibiotic therapy for decades to come.