The battle against antibiotic resistance has been going on for years and, unfortunately, bacteria, particularly multi-resistant organisms, continue to be formidable enemies. Furthermore, the scale of the problem is increasing. The Centers for Disease Control and Prevention, for example, reports 2.8 million resistant infections each year in the United States.
This growing threat also carries significant direct and indirect costs. Direct costs are increasing due to delayed pathogen identification, longer hospital stays, and higher-acuity care with more complex patients to manage. Indirect costs include lost productivity and overall economic deficiencies.
However, it is not time to give up. Progress has been made to stay ahead of resistant bacteria, with Roche announcing on May 26, 2025 that its antibiotic zosurabalpin was entering phase 3 clinical trials. If development continues, zosurabalpine could become the first in a new class of antibiotics approved by the FDA since 1968 to treat Gram-negative infections. Contrary to widely held beliefs, there are economic incentives to develop other novel antibiotics – either with new mechanisms of action or with new classes of agents. These incentives take the form of UK business initiatives and public-private partnerships between the US government and entrepreneurial companies.
Technology to the rescue?
Faster, more accurate diagnostic capabilities allow healthcare providers to identify the precise pathogen(s) or “superbugs” causing these infections, eliminating the need for lengthy courses of broad-spectrum antibiotics. Empirical therapy is well-intentioned but can strengthen the ranks of resistant organisms. Instead, rapid diagnostics using polymerase chain reaction (PCR) analysis can provide results in 24 hours compared to up to 5 days with culture testing, allowing for more targeted and effective therapy.
PCR has long been a reliable, rapid and accurate method for the detection of pathogens. From conventional PCR to real-time PCR, technology continues to be an essential tool for detecting pathogens, identifying resistant strains, and guiding antibiotic stewardship. In fact, for management to be effective, you need to know precisely what pathogen you are dealing with.
Confirmation of the pathogen you suspect is causing the resistance can be achieved with a single PCR test, but looking for one bacteria at a time may be ineffective. In contrast, multiplex PCR panels can save the laboratory time and money by evaluating the same sample for multiple bacteria.
The latest weapon in the fight against antibiotic resistance could be artificial intelligence. Some experts predict that AI will reveal new therapeutic targets and speed up the research and development process through increased efficiency. In short, rapid DNA sequencing and AI models could help researchers predict resistance.
In an effort to look backward to move forward, scientists at the University of Pennsylvania have even turned to ancient DNA for answers. Using machine learning, researchers are examining the DNA of Neanderthals, woolly mammoths, giant sloths and other animals that once roamed the Earth in search of peptides that impart antibiotic properties. They have called this process “molecular dequenching” and hope to generate new therapies using bioactive molecules that are no longer encoded by living organisms today.
Making antibiotics financially attractive
Developing antibiotics in 2025 is not financially feasible for many companies. Even if they understand the dangers of growing antibiotic resistance, the return on investment simply isn’t there. For example, Wellcome estimates that it will take 10 to 15 years and more than a billion dollars to develop a new antibiotic.
The UK is taking an innovative approach by paying companies to develop much-needed new antibiotics. It has been described as a “Netflix-style” payment model in which the government’s National Health Service pays a fixed annual fee for access to two new antibiotics: Pfizer’s Zavicefta (ceftazidime/avibactam) and Shionogi’s Fetcroja (cefiderocol). Payments are not tied to market volume, so the focus is more on creating solutions. Closer to home, the PASTEUR Act was reintroduced in Congress in 2023 to create a similar incentive, but has not yet been passed into law.
Fund initial research
The U.S. government has also partnered with private companies to support the development of new antibiotics. The goal is to fund early research and serve as a bridge to bring promising products to a stage where pharmaceutical companies will take over development. Recognizing the seriousness of the threat posed by resistant bacteria, the government includes these efforts within the Chemical, Biological, Radiological, and Nuclear Threat Division of the Center for Biomedical Advance Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services.
BARDA has supported six antibiotics with new formulations or a new indication that ultimately received FDA approval, including Blujepa (gepotidacin), EMBLAVEO (aztreonam-avibactam), ZEVTERA (ceftobiprole medocaril sodium for injection), Xerava (eravacycline for injection), ZEMDRI (plazomicin) injection and Vabomere. (carbavance). BARDA also partnered with the National Institute of Allergy and Infectious Diseases (NIAID) and Wellcome to create the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) initiative. CARB-X also identifies and funds innovative early-stage antibacterials and provides companies with expert guidance to reach the clinical market. BARDA provided an initial $200 million to the CARB-X collaboration, and over the past year it has become the world’s largest public-private partnership dedicated to early-stage product development against antimicrobial resistance.
A global threat
In the meantime, before these efforts lead to new antibiotics, there are still gaps to be filled. Animals treated with antibiotics can introduce resistant bacteria into the food supply. Another source is environmental runoff from the lands where these animals are raised. The combination of efforts to address human, animal and environmental threats is called the One Health approach and can help promote antibiotic stewardship.
Furthermore, given the global nature of antibiotic resistance, initiatives are needed to encourage low- and middle-income countries to adopt antibiotic stewardship and other strategies to reduce risks. This is also true in global conflict zones, where the growing threat of antibiotic resistance may not be a priority for public health officials and healthcare providers.
The Center for Global Development emphasizes that the investments are aimed at improving the treatment of bacterial infections. Increasing access to antibiotics, including new antibiotics worldwide, will also provide significant health and economic benefits. Without these efforts, the Center predicts, for example, that health care costs in high-income countries will increase by $176 billion each year. Additionally, the global economic return from increasing resistance could be $1.7 trillion less per year than in a world without antimicrobial resistance.
Harvard University researchers also examined the global burden of antimicrobial resistance from 1990 to 2021 and predicted changes through 2050. They analyzed death records, hospital discharge information and microbiological data to examine historical trends and future scenarios in 204 countries. They found that higher-risk populations, such as older adults, are likely to experience the greatest increase in drug-resistant bacterial infections. Policymakers should emphasize interventions that meet the unique needs of different regions of the world, improve antibiotic stewardship and PCR surveillance programs, and increase global collaboration so that data and resources can be shared globally.
A way forward
Antibiotic resistance poses a growing global threat with serious health and economic consequences. Yet progress has been made – from rapid PCR diagnostics and AI-based research to new drug development and innovative financing models. Continued collaboration, smarter management and equitable access will be essential to staying ahead of this high-stakes fight.
Photo: Flickr user Purple Sheep
Greer Massey, PhD, is Chief Scientific Officer at Molecular Designs and guides the development of multiplex PCR assays for research, as well as complementary reagents and instrumentation. Previously, Dr. Massey led research and development at Assurance Scientific, where she led efforts to obtain SARS-CoV-2 emergency use authorization for symptomatic and asymptomatic testing. She also helped establish the counseling services. Prior to that, Dr. Massey led the bioanalytical department at Southern Research and developed multiplex assays and their lyophilization as senior product manager at BioGX, Inc. Dr. Massey received his MS in Biology and PhD in Microbiology from the University of Alabama at Birmingham.
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