New Antibiotics Provide a Glimmer of Hope as Older Drugs Grapple With Resistance

The discovery of penicillin by Alexander Fleming in 1928 ushered in a new era for science, medicine, and humanity. Antibiotics have been celebrated as ushering in a new era of modern medicine. Described as one of the greatest public health achievements of the 20th century, they have improved life expectancy and child survival rates worldwide.¹

However, this herculean achievement has been fraught with incessant challenges. The development of antibiotics may have lagged, perhaps because they are not as lucrative as medications for chronic conditions. Bacteria have evolved ways to evade even the most effective antimicrobial agents, leading to antimicrobial resistance (AMR).²

Antimicrobial resistance (AMR) is currently one of humanity’s most important biological threats. The World Health Organization says AMR could potentially contribute to around 10 million global deaths every year by 2050.³ This figure is higher than the estimates for cancer. A 2023 Lancet study found that AMR directly caused 1.27 million deaths in 2019. In the same year, 4.95 million more deaths could be indirectly linked to it, with vulnerable groups like immunocompromised patients and the elderly being disproportionately affected. ⁴

Even in hospitals, superbugs such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae are thriving. Hard to treat, they can make even routine procedures deadly.⁵ A small surgery could result in an intensive care unit admission if methicillin-resistant Staphylococcus aureus finds its way into a wound. There is also an increase in the incidence of “super gonorrhea,” caused by multidrug-resistant Neisseria gonorrhoeae.

Gonorrhea was once treatable with penicillin. When it became resistant, clinicians turned to cephalosporins. The same bacteria now resist treatment with ceftriaxone, the last resort, even in the US and Europe.⁶ The CDC reports up to 1,600,000 new cases of gonorrhea every year in the US. More than half of these cases are resistant to at least one drug.⁷

The increasing rates of AMR can be attributed to overprescription, underprescription, drug abuse, nonadherence, agricultural overuse, and counterfeiting.⁸

Many prescribed antibiotics are unnecessary, as some erroneously treated diseases are self-limiting and not caused by bacteria. Even when prescribed correctly, some patients are unable to stick to the course of their antibiotic treatment until the end. Incomplete treatment gives lurking bacteria a chance to regrow and adapt. Similarly, agricultural overuse accelerates bacterial evolution. In low-resource settings, counterfeiting also contributes.⁹

Clinicians face a confusing dilemma. Prescribing empirical medications can further increase AMR. Waiting for culture samples delays care. One is forced to ask: Why not just create a new antibiotic?

Fortunately, there is fresh hope as researchers are making progress in antibiotic research. They have found candidates in once-overlooked areas such as soil bacteria and AI-driven design. Their discoveries promise to outwit superbugs and improve antibiotic treatment, providing clinicians with more options and reducing delays.

“The discovery of new antibiotics is overdue. For decades, development lagged due to scientific complexity and the ‘innovation paradox’ where research focused on modifying old drug classes rather than pioneering new ones, but thankfully that landscape is shifting now,” says Ahsan Bhatti, MA, superintendent pharmacist and founder of Quick Meds Online Pharmacy.

For 30 years (1987 to 2017), no novel antibiotics were discovered and approved. The last class, oxazolidinones, was discovered in 1987 and approved by the Food and Drug Administration in 2020. Clinicians have therefore been forced to turn to tweaked antibiotics that have not been very effective against evolving superbugs.

Economic and regulatory challenges persist.¹⁰ “Many easily targetable bacterial pathways have already been exploited, making true mechanistic innovation difficult. At the same time, stewardship programs appropriately reserve new agents to prevent resistance, which limits market return compared to chronic-disease drugs. Regulatory hurdles and complex non-inferiority trial designs add additional cost and risk, contributing to a fragile antibiotic pipeline,” says Kimberly Sukhum, PhD, head of science at Tiny Health.

Antibiotics, like other drugs, are expensive to make. Developing and distributing one product can exceed $1 billion.¹¹ They also have a short market life. Bacteria can become resistant to new antimicrobials in 2 to 3 years.¹²

A study found that antibiotics yield a lower return on investment than other drugs.¹³ This suggests why pharma companies are reluctant to invest in them. Of what use is making a drug that will remain on shelves, unused, reserved as a “last resort?”

Regulatory standards also have an impact. The Food and Drug Administration, for example, demands phase 3 trials for resistant infections.¹⁴ The small number of approved antibiotics also discourages venture capital investment.

In 2015, Slava Epstein, PhD, MS, used isolation chips that mimicked the soil’s diffuse nutrients to awaken microbes that had previously been impossible to culture in labs. 99% of microbes refuse to grow in labs.¹⁵ This led to the discovery of teixobactin from Eleftheria terrae, a drug that targets the cell wall in gram-positive bacteria like MRSA and vancomycin-resistant Enterococci (CRE). Phase 1 trials conducted in 2024 suggest the drug is safe. No resistance was observed in laboratory studies at 27 days. Unlike vancomycin, teixobactin evades bacterial pumps. It primarily binds to lipid molecules, the building blocks of the bacterial cell wall.¹⁶

In Japan, Murayamycin, also derived from soil bacteria, is effective against resistant strains of Escherichia coli.¹⁷ A paper published in 2024 has shown that answers do not only lie in soil. In fact, they can lie in the most unusual places, even in the human nose. Lugdunin, derived from human nose staph, was seen to wipe out MRSA biofilms.¹⁸

The role of AI cannot be overlooked. Nature published a study conducted by researchers at MIT and Harvard who used AI models to design halicin, a drug that effectively kills many drug-resistant bacteria. Made from piolitazone and named after a fictional AI system, it killed 35 out of 36 known drug-resistant bacteria (except Pseudomonas aeruginosa). It showed efficacy against Acinetobacter baumannii, Clostridioides difficile, Mycobacterium tuberculosis, and carbapenem-resistant Enterobacteriaceae. The AI model was trained on 2500 molecules, 1700 of which were FDA-approved products.¹⁹ Halicin is yet to undergo human trials.

MIT also discovered Abaucin, a potent drug against A baumanii, by letting an AI model observe 7500 molecules that inhibit A baumanii growth. The machine discovered Abaucin, which controlled infection in murine models and shows promise.²⁰

Phage therapy, like AI, continues to evolve. Some engineered viruses, such as Armata’s AP-PA02, can kill resistant Pseudomonas.²¹ Odilorhabdinus, derived from nematodes, is effective against Gram negatives.²² And Zosurabalpin (2024) kills gram-negative bacteria by breaching their membranes. Human trials with the drug might begin soon.²³

For clinicians, these recent discoveries offer opportunities for partnership between AI and professionals, in which AI predicts resistance patterns by analyzing genomes, and clinicians make informed choices to treat diseases.

With increased space, clinicians have greater capacity to act, but maintaining vigilance is essential. Hospitals should continue to enhance stewardship programs to optimize drug selection, dosing, and treatment duration without delaying essential care. Ongoing surveillance is vital for early identification of resistance patterns. Incorporating microbiome testing into stewardship processes offers a new opportunity. Knowing a patient's microbial baseline and recovery path can help tailor personalized infection prevention approaches.

Experts stress the need for holistic solutions. “New antibiotics are a critical part of the solution, but they cannot succeed in isolation. Diagnostics and antimicrobial stewardship are what ensure these therapies are used appropriately, preserved longer, and delivered to the right patients at the right time,” says John Hurst, PharmD, BCIDP, MBA, senior director, field medical affairs at bioMérieux.

For humanity, the gains are profound. With new antibiotics, AMR-related mortality drops significantly. Surgeries become safer, and the economic burden of bacterial diseases decreases. People become less afraid of contracting “superbugs.” And with adequate health promotion and education, they can become more aware of what AMR is and understand the part they can play in stopping it.

Pharmacological surveillance will have to evolve alongside these discoveries, going beyond just reporting to include genomic surveillance, AI-assisted resistance analysis, and global data sharing.

We must all be involved in the fight against AMR. And perhaps with willpower, better research, and some help from AI, we can win.

References:

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