Phage Therapy as a Self-Replicating Strategy for Besieged Health Systems.

Abstract

Background: Active conflict zones and resource-limited health settings face compounding challenges from disrupted antibiotic supply chains concurrent with the proliferation of multidrug-resistant (MDR) and pan-drug-resistant (PDR) pathogens. In such settings, drug availability directly determines clinical outcomes.

Methods: A narrative review of the literature was conducted in accordance with adapted SANRA (Scale for the Assessment of Narrative Review Articles) criteria, searching PubMed/MEDLINE, EMBASE, Cochrane Library, and grey literature sources for articles published between 1^st January 2001 and 1^st April 2026. Of 8003 records identified, 42 met inclusion criteria and were incorporated into this review Seminal pre-2001 works and non-English-language sources from Eastern European phage therapy programmes were deliberately included to mitigate geographic publication bias.

Main findings: Bacteriophages possess unique pharmacokinetic properties, including self-replication exclusively at infection sites, enabling pathogen clearance from a minimal dose burden. The Phage Support Ukraine (PhageSP UKR) initiative demonstrated rapid local phage isolation against circulating MDR and PDR Klebsiella pneumoniae strains from combat casualties, bypassing conventional pharmaceutical manufacturing chains. In a subset of strains, phage-driven evolutionary tradeoffs can compel ESKAPE pathogensto shed resistance plasmids, including NDM-1metallo-β-lactamase determinants, re-sensitizing the effected strains to existing antibiotics - a strain-specific phenomenon rather than a general clinical outcome These effects act synergistically with host immune defences. Decades of data from the Eliava Institute and growing compassionate use evidence provide a foundational safety profile. The PhagoBurn randomised trial found bacterial burden reduction to be significantly slower with phage therapy than standard of care, a result attributable to subtherapeutic dosing in a substantial proportion of participants; it does not establish efficacy but highlights dose-optimisation as a critical unmet need prior to wider deployment.

Conclusion: Bacteriophage therapy represents a biologically rational and logistically feasible intervention for health systems under siege. While large-scale randomised controlled trial evidence remains limited, pragmatic deployment supported by compassionate use data and adaptive regulatory frameworks provides justification for clinical application against otherwise untreatable infections in conflict and resource-limited settings. Targeted investments in phage biobanking, rapid point-of-care production protocols, and harmonized international regulatory pathways are urgently needed.