Phage cocktails - state-of-the-art technologies and strategies for effective design

Sep 30, 2026

With the growing severity of antimicrobial resistance (AMR), phage therapy has drawn increasing attention as a novel therapeutic alternative. Phage cocktails that combine multiple bacteriophages can broaden antimicrobial spectra beyond single-phage use and may reduce the rise of resistant bacteria. This review systematically analyzes advanced technologies and design strategies, highlighting receptor-diverse phage combinations, approaches based on phage–bacteria infection network analysis, and synergistic effects with antibiotics. Large-scale clinical evidence is evaluated to clarify implementation challenges, including cocktail stability, quality control, and immune responses, informing future AMR-focused therapies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages27

Reading Time1 h 8 min

AccessFree to download

Introduction

Antimicrobial resistance and AMR burden

Phage therapy and rationale for renewed adoption

Advantages of phage cocktails over single-phage use

Design challenges and practical implementation issues

Abstract

Keywords

FEMS Microbiology Reviews, 2026, 50, fuaf061 DOI: 10.1093/femsre/fuaf061 Advance access publication date: 8 December 2025 Review Article Phage cocktails: state-of-the-art technologies and strategies for effective design Tomoyoshi Kaneko 1,2 , Kanata Nakatsuka 1,2 , Satoshi Tsuneda 1,2 ,* 1 Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan 2 Phage Therapy Institute, Comprehensive Research Organization, Waseda University, Tokyo, 162-8480, Japan ∗ Corresponding author. TWIns, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan. E-mail: [stsuneda@waseda.jp](stsuneda@waseda.jp) Editor: Grzegorz Wegrzyn Abstract With the growing severity of antimicrobial resistance (AMR), phage therapy has garnered attention as a novel therapeutic alternative. In particular, phage cocktails, which combine multiple phages, potentially offer broader antimicrobial spectra than single-phage applications and may suppress the emergence of resistant bacteria. This comprehensive review systematically examines cuttingedge technologies and effective strategies for designing phage cocktails. Special attention was given to the combination of phages recognizing different receptors, designs based on phage-bacteria infection network analysis, and synergistic effects with antibiotics. Additionally, the analysis of large-scale clinical studies has identified challenges in practical implementation, including ensuring cocktail stability and addressing immune responses. These insights are expected to contribute to the design of more effective phage cocktails and the establishment of novel therapeutic strategies to address AMR. Keywords: phage therapy; phage cocktail; phage resistance; ESKAPE; AMR; bacteriophage; clinical application Introduction In recent years, the antimicrobial resistance (AMR) crisis has continued to escalate, necessitating the urgent development of novel infectious disease treatment modalities (Papanicolaou et al. 1990 , Horii et al. 1993 , Doi et al. 2002 , Mirzaei and Nilsson 2015) . The World Health Organization recognizes AMR as a critical challenge and promotes countermeasures (Lawe Davies 2017) . In particular, a group of pathogenic bacteria collectively known as ESKAPE (Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) has acquired substantial multidrug resistance, presenting serious problems in clinical settings (Rice 2008) . Additionally, Escherichia coli , although not part of the original ESKAPE classification, represents another critical priority pathogen owing to its widespread antibiotic resistance and clinical relevance. A comprehensive analysis published in 2024 estimated that AMR was associated with 4.71 million deaths in 2021, with 1.14 million directly attributable to AMR, and estimated that annual deaths attributable to AMR will increase to 1.91 million by 2050 (Naghavi et al. 2024) . Furthermore, the authors predicted that the cumulative number of deaths attributable to AMR between 2025 and 2050 would approach 39.1 million (Naghaviet al. 2024) . Under these circumstances, infectious disease treatments utilizing bacteriophages (phages), which are viruses that infect bacteria, have garnered attention. As recently outlined by Skurnik et al. , phage therapy was temporarily eclipsed by the widespread adoption of antibiotics. Nevertheless, with the intensification of the AMR crisis and advancements in modern technology, the value of phage therapy, which offers specific antibacterial action with minimal side effects, is being re-evaluated on a more scientific foundation (Skurnik et al. 2025) . In phage therapy, the use of phage cocktails (combinations of multiple phages) furnishes numerous advantages over singlephage applications. First, a broader antimicrobial spectrum can be achieved (Chen et al. 2024) . Given that several phages exhibit extremely narrow host

FAQs

Why are phage cocktails considered promising for AMR?

Phage cocktails combine multiple phages to widen antimicrobial spectra and can suppress the emergence of phage-resistant bacteria compared with single-phage applications.

What design strategies does the review emphasize for effective phage cocktails?

The review highlights combining phages that recognize different bacterial receptors, using phage–bacteria infection network analysis for design, and considering synergistic effects with antibiotics.

What practical challenges are identified for clinical implementation?

Key challenges include ensuring cocktail stability and quality control, and addressing immune responses and antibody production that may affect therapeutic efficacy.

Sep 30, 2026

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