Pharmacology of Bacteriophage Therapy in Children: A Re-Emerging Paradigm in Antibacterial Therapy.

Abstract

The rise of antibiotic-resistant bacteria has reignited global interest in bacteriophages as potential therapeutic agents. Bacteriophage (phage) therapy provides an alternative to conventional antibiotics to treat serious infections caused by multidrug-resistant pathogens. In this narrative review, we explore the pharmacokinetics (PK), pharmacodynamics (PD), and clinical use of phage therapy in pediatric populations. We conducted PubMed searches for relevant publications from 1959 to September 2025. In contrast to most drugs, phages are self-replicating in the presence of target bacteria, necessitating the use of non-linear, dynamic pharmacology models to integrate phage-bacteria interaction (which can fluctuate over time, based on the presence of susceptible bacteria), as well as host factors such as immune clearance of phages and traditional host mechanisms of clearance of invasive bacterial pathogens. Phages are primarily cleared through the reticuloendothelial system, particularly in the liver and spleen. Advantages of phage therapy over antibiotics include a promising safety profile, preservation of the child's own microbiome, and, compared with some antibiotics, enhanced penetration into biofilms. Our knowledge of the benefits and risks of phage therapy is limited largely to current pediatric case reports and case series. The clinical use spans a wide breadth of clinical infections, mostly involving poorly responsive infections caused by multidrug-resistant bacteria. Until robust, prospective PK-PD and clinical trial data become available to guide therapy, phage therapy should be administered under protocols with individualized dosing and rigorous safety monitoring. Clinical applications using standardized, evidence-based dosing regimens and outcome assessments require further evaluation.