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With the global rise in antimicrobial resistance, there has been a renewed interest in the application of therapeutic phages to treat bacterial infections. Therapeutic phage monitoring (TPM) is proposed as an essential element of phage therapy (PT) protocols to generate data and fill knowledge gaps regarding the in vivo efficacy of therapeutic phages, patients' immune responses to PT, and the wider ecological effects of PT. By monitoring phage concentrations in blood and tissues, together with immune responses and possible ecological changes during PT, TPM may enable the optimization of dosing and the implementation of precision medicine approaches. Furthermore, TPM can validate diagnostic surrogates of efficacy, direct research efforts, and establish quality assurance indicators for therapeutic phage products. Thus, TPM holds great potential for enhancing our understanding of the multidirectional phage–bacteria–host interactions and advancing "best practice" PT, ultimately improving patient care. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages) have shown great potential as natural antimicrobials against extracellular pathogens (eg, Escherichia coli or Klebsiella pneumoniae), but little is known about how they interact with intracellular targets (eg, Shigella spp. Salmonella spp. Mycobacterium spp.) in the mammalian host. Recent research has demonstrated that phages can enter human cells. However, for the design of successful clinical applications, further investigation is required to define their subcellular behavior and to understand the complex biological processes that underlie the interaction with their bacterial targets. In this review, we summarize the molecular evidence of phage internalization in eucaryotic cells, with specific focus on proof of phage activity against their bacterial targets within the eucaryotic host, and the current proposed strategies to overcome poor penetrance issues that may impact therapeutic use against the most clinically relevant intracellular pathogens. [ABSTRACT FROM AUTHOR]