The global rise of antimicrobial resistance has renewed interest in bacteriophages (phages) as targeted therapeutics for difficult-to-treat bacterial infections. This consensus guideline seeks to close practical gaps that currently impede safe, standardized clinical use of personalized phage therapy, by translating foundational principles into actionable recommendations for real-world settings. The document focuses on core principles, infrastructure, preparation and quality control, clinical administration and research priorities to enable responsible integration alongside conventional antimicrobial approaches.
The guideline was developed within the methodological framework of the Association of the Scientific Medical Societies in Germany (AWMF) and led by the German Society for Infectious Diseases. The panel included representatives from 20 German medical societies, patient advocacy groups, regulatory authorities and 18 international experts. A steering committee supervised six topic-specific working groups, which performed literature reviews and drafted recommendations.
Consensus was achieved through six online conferences moderated by AWMF representatives; recommendations were voted on, amended as needed and graded. Recommendation strength used standardized wording: strong (grade A), conditional (grade B) and optional. The strength of consensus was categorized based on the proportion approving participants. Expository content not requiring action was labeled as statements and not formally graded.
The guideline targets physicians treating adult and pediatric bacterial infections—especially those working in infectious disease management and antimicrobial stewardship—alongside pharmacists, microbiologists, researchers, regulatory bodies, patient organizations, hospital administrators and industry stakeholders. It does not attempt to cover every clinical scenario but provides a structured framework to support clinicians, pharmacists, researchers and policymakers in navigating personalized phage therapy.
Phage therapy, historically used for enteric and wound infections, is experiencing renewed clinical interest. Lytic phages form the basis of therapeutic approaches. Key implementation challenges include phage specificity requiring individualized matching, evolving bacteria–phage dynamics, and limitations of standard regulatory pathways based on GMP-manufactured investigational medicinal products and randomized controlled trials.
The guideline acknowledges that GMP manufacture can be costly, time-consuming and incompatible with the flexibility needed for individualized treatment. As pragmatic alternatives, the document discusses the role of magistral preparation of phage APIs and PTMPs, which in many jurisdictions are exempt from GMP requirements (for example under Article 3(1) of Directive 2001/83/EC in the EU). However, current professional guidance lacks practical detail to ensure consistent preparation, traceability and stability across sites.
Phage therapy should be considered case by case, primarily for patients in whom standard-of-care treatments have failed or are contraindicated. Because of high specificity, successful treatment depends on culture-based bacterial identification with species determination followed by careful phage susceptibility matching. Susceptibility should be confirmed as close to treatment initiation as possible; in urgent cases, therapy may start empirically and be adapted when results are available.
In polymicrobial infections, all causative species should undergo susceptibility testing. Interdisciplinary discussions among treating clinicians, microbiologists, infectious diseases specialists and experts in phage selection and manufacturing are essential. When prepared and administered under adequate quality standards, phage therapy appears generally safe across diverse patient groups, although monitoring is advised.
Safe and scalable implementation requires coordinated infrastructure integrating laboratory diagnostics, phage preparation and clinical expertise. Core elements include access to phage laboratories for screening and susceptibility testing, facilities for phage preparation with defined quality control and safety standards, and an interdisciplinary phage therapy board to guide case assessment and individualized strategies.
These elements need not be collocated; preparation or specialized testing may be outsourced to defined centers. Institutions providing phage therapy must meet minimum requirements—appropriate storage, medically qualified personnel, capacity to administer phages, monitor safety, manage concomitant therapies and perform microbiological sampling. External laboratories may be used if results are timely.
Standardized, harmonized methods for susceptibility and potency testing and interlaboratory proficiency testing are emphasized. Referential guidance in development by EUCAST’s phage susceptibility testing subcommittee is noted. Comprehensive documentation in national or international registries is recommended to improve transparency and inform future practice.
The guideline highlights practical trade-offs between GMP manufacture and magistral or non-GMP approaches. GMP-grade phage manufacture is resource-intensive and may be infeasible when individualized phage matching or rapid adaptation is required. Magistral preparation of phage APIs and finished PTMPs represents a pragmatic route in many regions, but the guideline stresses the need for clearer, practice-oriented standards for consistent preparation, traceability, stability (including cold-chain considerations), and liability management.
Quality assurance, documentation and defined release criteria are presented as essential, together with infrastructure that supports safe transfers when cross-border or interinstitutional movement of preparations is necessary. The guideline cautions that in many countries cross-border transfer of magistral preparations is logistically and legally challenging.
Clinical use should proceed with interdisciplinary oversight. Relevant activities include confirmation of bacterial identity and susceptibility, selection and documentation of phage preparations, dosing and route decisions adapted to infection site, and active monitoring for expected biological responses (for example transient fever or byproducts of bacterial lysis). No major phage-attributable allergic reactions or clinically relevant drug interactions have been consistently reported in available data, but vigilance and structured monitoring are advised.
Comprehensive case documentation—treatment protocols, outcomes and unexpected events—in registries is recommended to support transparency, enable systematic evaluation and inform future recommendations.
Available evidence suggests a generally favorable safety profile when phages are produced and administered according to quality standards. Case series and systematic reviews report safety across varied patient groups, but controlled demonstration of efficacy is limited. A recent systematic review noted that trial designs often failed to deliver sufficient quantities of appropriately matched phages to infection sites, contributing to inconsistent efficacy signals.
Assays used for assessing phage activity include plaque, spot and liquid infection assays to generate phagograms, but interlaboratory reproducibility is limited. Heterogeneous treatment approaches, variable manufacturing quality and the individualized nature of therapy are cited as key factors complicating evidence synthesis and regulatory alignment.
The guideline identifies the need for optimized treatment strategies and well-designed prospective trials that account for phage specificity, dosing, delivery to infection sites and adaptive therapy approaches. Standardization of susceptibility and potency testing and establishment of interlaboratory proficiency programs are research priorities. The guideline also calls for high-quality, harmonized registry data to enable systematic outcome analyses and to inform future trial design and regulatory pathways.
The guideline is valid from 5 January 2026 to 29 June 2030. The steering committee will initiate revisions and review the need for updates annually. All participants submitted conflict-of-interest declarations; moderate COIs were identified for seven individuals who were excluded from leadership roles. Consensus analyses were repeated including and excluding their votes and showed no change in outcomes. The guideline was externally reviewed and adopted by participating societies and circulated for support by international stakeholders.