Table 2.

Challenges of phage therapy against mycobacterial infections, from the selection of phages, the necessary regulatory approvals and treatment considerations.

Challenges of Phage Therapy Against Mycobacterial Infections
Selection of phages	Laborious screening process of thousands of different phages A cocktail of 3 to 6 active phages may be needed Few centers in the world are able to perform this personalized manufacturing
Administration	Intravenous route for disseminated infection is required Topical administration for skin lesion is easily performed Still under development: Use of a nonvirulent mycobacterium as carrier to reach the lung Liposomal formulations for inhalation in case of lung infection
Development of resistance	Intrinsically resistance strain (i.e., smooth morphotype of M. abscessus) Acquired resistance after treatment/bacterial defense mechanisms Production of neutralizing antibody against the phages
Regulatory process	Each clinical case required multiple local approvals, including ethical committee and national approval body Genetic characterization of the phage(s), sterility of the final product and minimal endotoxin concentration required prior to approval