Clinical phage microbiology: a narrative summary

Abstract

Background: Although phage therapy has been in existence for a century, a recent resurgence in interest has occurred because of the continued emergence of antimicrobial resistance and the rising use of indwelling medical devices, resulting in biofilm-associated infections, for which conventional antibiotics are of limited use. Despite this, the clinical successes have been inconsistent because of multiple reasons, including (1) the narrow host range of phages, (2) challenges with concentrating phages at the site of infection, (3) development of resistance of bacteria to phages and (4) immune neutralization. Microbiologic assays have the potential to help guide the course of clinical therapy and improve outcomes. Methods developed decades ago remain the mainstay of phage diagnostics and recently, newer diagnostics are closing the gap needed to further advance clinical phage therapy.

Objectives: To review the current state of clinical phage microbiology and identify gaps.

Sources: A PubMed search was performed using the terms "phage microbiology", "phage susceptibility test", "phage host range", "phage biofilm", and "phage therapeutic monitoring".

Content: Phage susceptibility testing, biofilm assays, phage-antibiotic combination testing, therapeutic drug monitoring, and immune monitoring assays are the current foundation for clinical phage diagnostics. Standardization of these assays and better understanding as to if and how they should be used in terms of clinical management of patients receiving phage therapy is needed.

Implications: A substantial gap between in vitro studies and in vivo outcomes indicates that further work is needed in phage pharmacokinetics to accurately assay phage particles at the site of infection; recapitulate in vivo biofilm; capture the complex interactions between phages and antibiotics, phages and their target bacteria, among phages in a cocktail, and with the superhost immune system.

Keywords: Biofilms; Phage susceptibility testing; Phages; Therapeutic monitoring.