Bacteriophages in Medicine: A New Frontier Against Antibiotic Resistance

Antimicrobial resistance (AMR) has become a major global health crisis. According to the World Health Organization, drug-resistant bacterial infections were directly responsible for 1.27 million deaths in 2019, with nearly five million deaths associated with bacterial resistance more broadly. The situation is worsening as bacteria evolve resistance faster than pharmaceutical companies can produce new antibiotics. This leaves millions vulnerable to infections once considered treatable. The overuse and misuse of antibiotics in both human and veterinary medicine, as well as in agriculture, have accelerated this resistance. The clinical pipeline for new antimicrobial drugs is alarmingly thin, especially for pathogens classified as critical or high priority by the WHO. As infections become increasingly difficult to manage, scientists and clinicians are revisiting an older approach: bacteriophage therapy.

Bacteriophages, or simply phages, are viruses that infect bacteria. First described in the early 20th century by Frederick Twort and Félix d’Herelle, phages were used therapeutically in several countries before antibiotics became widely available. Each phage is highly specific to its bacterial host and infects it by attaching to surface receptors and injecting its genetic material. There are two main types of phage replication cycles: the lytic and the lysogenic. In the lytic cycle, the phage takes over the bacterial cell machinery to replicate, leading to cell lysis and the release of new virions. In contrast, during the lysogenic cycle, the phage genome integrates into the host genome and remains dormant until activated, at which point it enters the lytic phase. Most therapeutic applications focus on strictly lytic phages due to their ability to rapidly eliminate bacterial populations. Phages are found wherever bacteria exist, including oceans, soil, sewage, and the human microbiome, and are considered the most abundant biological entities on Earth.

As antibiotic resistance grows, the interest in phage therapy has been revitalized, especially for infections where conventional drugs fail. Phages offer a range of potential advantages. Their specificity allows them to target harmful bacteria without damaging beneficial microbiota, unlike broad-spectrum antibiotics. They are self-replicating in the presence of their target bacteria, meaning they increase in number at the site of infection until the bacterial population is cleared. Furthermore, phages can evolve alongside bacteria, offering a dynamic tool in contrast to static chemical drugs. This co-evolutionary potential has significant implications for long-term treatment efficacy, as phages can adapt to overcome emerging resistance mechanisms.

Delivering phages to the body depends on the nature and location of the infection. Options include oral administration, topical application, aerosolized delivery for respiratory infections, and intravenous injection for systemic or localized deep tissue infections. In most cases, treatment requires either the use of a single known-effective phage or a “cocktail” of multiple phages to broaden efficacy and limit resistance. Personalized phage therapy, in which specific phages are selected based on the patient’s infecting bacterial strain, has gained attention and shown success in clinical settings. For example, a compassionate-use case in France involved a life-threatening Acinetobacter baumannii infection successfully treated with a customized phage cocktail, developed and delivered after antibiotics failed. In other documented instances, patients with chronic Pseudomonas aeruginosa or Mycobacterium abscessus infections have responded positively to phage therapy, especially in cases of cystic fibrosis or post-transplant immune suppression.

Despite these successes, phage therapy faces several critical challenges. Matching the correct phage to a specific bacterial strain is time-intensive, and although growing efforts are underway to build large phage banks, they remain limited. Regulatory approval is another barrier. Phages are biological agents, and their variability conflicts with the standardized, fixed composition typically required for drug approvals. Moreover, while phages can evolve to counter bacterial resistance, bacteria can also develop mechanisms to block phage infection, such as modifying or masking receptor sites or deploying CRISPR-Cas systems. This makes treatment design complex and necessitates constant adaptation of phage libraries. Manufacturing phages at pharmaceutical grade and scale is also technically challenging, requiring clean production systems free from contaminants and endotoxins.

In some cases, failure of antibiotic treatment isn't due to resistance alone but to delivery issues, such as poor tissue perfusion. For example, an ischaemic toe or abscess with impaired vascular supply might prevent antibiotics from reaching therapeutic concentrations at the infection site. Phages, because of their ability to replicate locally, may offer advantages in such conditions, although evidence is still emerging.

Looking forward, the future of phage therapy is being shaped by advances in synthetic biology, genomics, and artificial intelligence. Researchers are engineering synthetic phages to expand host range, evade resistance, or deliver payloads like enzymes or CRISPR sequences. AI tools are being used to match phages to bacteria faster by analyzing bacterial genomes and predicting susceptibility profiles. Clinical trials are expanding in number, and regulatory frameworks are slowly adapting to accommodate these new forms of precision antimicrobials. Companies and academic institutions across Europe, North America, and Asia are working to standardize protocols and integrate phage therapy into hospital practices, particularly for multidrug-resistant infections in critical care.

In a world where traditional antibiotics are becoming less effective, bacteriophages offer a promising and biologically elegant alternative. While challenges remain, especially in regulation, logistics, and clinical integration, the therapeutic use of viruses to combat bacterial infections could play a key role in the post-antibiotic era. As the body of clinical evidence grows and technology enables more precise targeting, phage therapy may move from experimental use into mainstream practice. The very viruses that infect our bacterial enemies might become some of our most valuable allies.

Written By: Zlata Lukovych

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