Table 1.

Summary of main limitations to the use of bacteriophages.

Limitation	Description
Phage of Choice	Individual phages are insufficient for broad-spectrum infections; complex identification is needed. Elimination by the reticuloendothelial system reduces half-life, limiting efficacy.
Lysogenic Forms	Lysogenic phages confer poor results due to acquired immunity. Transduction of bacterial genome and potential transmission of harmful genes are concerns. Using multiple phages is often more effective.
Legal Limitations	Global regulatory variation in phage utilization. Permitted as a processing aid in certain countries, limited in the EU.
Purification and Stabilization	Phage characterization is essential for toxicity removal. Purification by ultracentrifugation or chromatography. Stability is crucial but varies among phages.
Dosage	High phage concentrations are needed for bacterial removal; lower doses are ineffective. Timing and delivery are critical, with potential for induced antibodies.
Terms of Use	Bacteriophage persistence varies with type, application conditions, and environmental factors. Refrigeration enhances persistence.
Resistance Mechanisms	Increased phage application may lead to bacterial resistance mechanisms. Coevolution cycles involve various resistance strategies.
Effectiveness	Efficacy is a major limitation; initial reduction is observed, but complete eradication is challenging. Factors influencing effectiveness include food matrix, pH, temperature, MOI, phagoresistance, and combination with other measures.