Phage therapy pharmacology: calculating phage dosing

Area of Science:

• Microbiology
• Virology
• Biotechnology

Background:

• Phage therapy, using bacteriophages (phages) to control bacteria, is a promising alternative to antibiotics.
• Rational development of phage therapy requires predictive dosing calculations.
• Current understanding of phage dosing parameters needs consolidation and accessible formulation.

Purpose of the Study:

• To provide a theoretical basis for phage therapy dosing calculations.
• To consolidate and present key concepts relevant to phage dosing in one location.
• To facilitate the rational development of phage therapy and biocontrol products.

Main Methods:

• Theoretical analysis of phage therapy dosing concepts.
• Derivation and presentation of formulae for key parameters.
• Discussion of the relative importance of various dosing factors.

Main Results:

• Exploration of concepts including minimum inhibitory concentration, minimum bactericidal concentration, decimal reduction time, and bacterial eradication time.
• Introduction of thresholds for phage population growth (proliferation threshold) and half-maximal growth rates (K(B)).
• Analysis of phage killing titers, multiplicity of infection, and peak phage densities.

Conclusions:

• Phage density is a critical factor in the efficacy of phage therapy for bacterial eradication.
• The presented calculations offer a framework for optimizing phage therapy dosing.
• Accessible formulae and derivations aid in the implementation and comparison of phage therapy strategies.