With antimicrobial resistance threatening millions of lives each year by mid-century, researchers are plotting a growing pipeline of new drugs, biological therapies, and technology-driven solutions that could redefine how infectious diseases are treated.
review: Antimicrobial resistance: the answer. Image credit: nobeastsofierce / Shutterstock
In a recently published narrative review, British Biomedical Journalresearchers summarized therapeutic approaches in development to address antimicrobial resistance (AMR).
The global burden of antimicrobial resistance and One Health strategies
AMR is a global concern with significant public health impacts in communities and healthcare settings. A 2016 report predicted that approximately 10 million people will die annually by 2050. A variety of strategies are being developed at local, national, and international levels to combat AMR under a multidisciplinary One Health approach, including surveillance, antimicrobial stewardship, infection prevention measures, and treatment innovations.
This review provided an overview of approaches currently under development to combat AMR, highlighting established treatments and experimental interventions. These include not only antibiotics, but also vaccines, bacteriophage therapy, immunotherapy, antimicrobial photodynamic and sonodynamic therapy, nitric oxide-based therapies, nanomaterial approaches, and enabling technologies such as artificial intelligence and organ-on-a-chip systems.
Recently approved antibiotics and their combinations
In the past decade, only 20 antibiotics, 4 nontraditional antibiotics, and 7 beta-lactam and beta-lactamase combinations have been introduced. Analyzes of antimicrobial drugs show that most drugs are derivatives of existing antibiotic classes and therefore may succumb to similar resistance mechanisms. Two recently approved first-in-class antibiotics include gepotidacin and lefamulin.
Lefamulin is a pleuromutilin that blocks protein synthesis by interfering with the 50S ribosomal RNA subunit. Approved by the Food and Drug Administration (F.D.A.) was used to treat community-acquired bacterial pneumonia in 2019. Gepotidacin, a triazaacenaphthylene, inhibits bacterial DNA replication by targeting topoisomerase enzymes. It was approved in 2025 to treat uncomplicated urinary tract infections in women and young people.
Embraveo, a combination of aztreonam and avibactam, was approved in 2025 for the treatment of adults with complicated intra-abdominal infections, nosocomial pneumonia, ventilator-associated pneumonia, complicated urinary tract infections including pyelonephritis, and aerobic gram-negative infections with limited treatment options. The drug had previously received marketing authorization from the European Medicines Agency in 2024. Zakuduro, a combination of sulbactam and dulobactam, has been approved to treat infections caused by: Acinetobacter baumannii calcoaceticus Complicated.
Novel antimicrobial peptide and oligonucleotide therapies
Antibacterial peptide (AMP), a natural component of the innate defenses of animals, plants, humans, insects and amphibians, has attracted great attention due to its antimicrobial properties and potential to modulate immune responses and modulate inflammatory processes. Of the more than 3,000 AMPs discovered to date, only seven have been approved, and all are derived from soil bacteria.
Zoslavalpine is a novel narrow-spectrum macrocyclic peptide that Acinetobacter baumannii We are planning to enter phase 3 clinical trials. Blocks lipopolysaccharide transport from the inner membrane to the outer membrane. A. Baumani. Current resistance mechanisms are not expected to affect zoslavalpine. Antimicrobial oligonucleotides are synthetic nucleic acid sequences that exert an inhibitory effect by binding to RNA through complementary base pairing.
Peptide-linked phosphorodiamidate morpholino oligomer (PPMO) has been reported to target conserved essential genes and reduce bacterial burden in animal models of infectious disease. Pseudomonas aeruginosa, Escherichia coli, A. Baumaniand Klebsiella pneumoniae. Bactericidal PPMOs also exhibit antibiofilm activity, inhibiting biofilm formation and reducing the amount of established biofilm.
Natural sources of antibacterial agents
Honey, particularly Manuka honey, has historically been used to treat wound infections. Recent studies have focused on its antibacterial effects against antibiotic-resistant pathogens. The antibacterial properties of honey are attributed to its physicochemical properties such as low water content, high osmolarity, and low pH, as well as its composition of hydrogen peroxide, defensin-1, methylglyoxal, and secondary metabolites.
Bee venom has shown antibacterial effects against multidrug-resistant bacteria (MDR) Contains pathogens Enterococcus faecalis, Escherichia coli, Staphylococcus aureusand Typhimurium. Spider venom has also been shown to contain AMP toxins that are valuable to humans. Staphylococcus aureus. Spices have been studied for their antibacterial activity, therapeutic properties, and adjuvant activity with conventional antibiotics against drug-resistant pathogens.
Microbiome-based therapy and fecal transplantation
Rebyota, the first live fecal microbiota-based biotherapy prepared from human donor feces and administered via enema, was approved in 2022 for the treatment of relapses. clostridioides difficile Infection (C.D.I.). In 2023, the first oral fecal microbiota therapy, Vowst, was approved. Studies highlight the effectiveness of fecal microbiota transplantation (FMT) Used in some clinical and laboratory settings to eliminate colonization and eliminate carriage of MDR bacteria and antibiotic resistance genes.
Eradication or eradication of MDR microorganisms in the intestine by FMT has been suggested to reduce infection risk and cross-contamination. Limited case reports and early studies suggest that FMT eliminated colonization of the gastrointestinal tract. Escherichia coli and Klebsiella pneumoniae Prevented adverse outcomes, including death, associated with MDR microorganisms in allogeneic hematopoietic cell transplant patients.
Predatory bacteria as living antibiotics
Predatory bacteria are considered live antibiotics because they can kill and ingest other bacteria. They are ubiquitous not only in soil but also in water environments such as rivers, seawater, and wastewater. Bdellobibrio Bacteriovorus is one such predatory bacteria that can kill Gram-negative bacteria within 30 minutes without inducing autolysis of its prey, thereby preventing the release of inflammatory molecules.
Gram-negative bacterial resistance is due to the fact that prey recognition and attachment do not depend on a single receptor, and enzymes that destroy the prey are upregulated upon invasion. B. Bacteriovorus It seems unlikely. Micabilio aeruginosavolus and B. Bacteriovorus has been shown to reduce the proliferation of Serratia marcescens Fluoroquinolone resistance Pseudomonas aeruginosa in animal infection models. These findings represent an experimental possibility rather than an established clinical therapy.
Emerging and under-research strategies to combat AMR
Increasing antibiotic resistance poses a global challenge in the treatment of infectious diseases. Although new treatment strategies and antimicrobial agents have been researched and developed to reduce AMR-related morbidity and mortality, many are still in the research phase and are not yet part of routine clinical practice.
Many new approaches are still in the preclinical and early clinical stages. Continued funding and interdisciplinary collaboration are essential for further development, evaluation, and transition to clinical care.