Occasionally, isolation of therapeutic phages can typically require a few months to complete, but clinics generally keep supplies of phage cocktails for the most common bacterial strains in a geographical area.The host specificity of phage therapy may make it necessary for clinics to make different cocktails for treatment of the same infection or disease because the bacterial components of such diseases may differ from region to region or even person to person.
In addition, due to the specificity of individual phages, for a high chance of success, a mixture of phages is often applied. This means that 'banks' containing many different phages are needed to be kept and regularly updated with new phages, which makes regulatory testing for safety harder and more expensive.
Phages in practice are applied orally, topically on infected wounds or spread onto surfaces, or used during surgical procedures. Injection is rarely used, avoiding any risks of trace chemical contaminants that may be present from the bacteria amplification stage,and recognizing that the immune system naturally fights against viruses introduced into the bloodstream or lymphatic system.
Phages can usually be freeze dried and turned into pills without materially impacting efficacy.
In pill form temperature stability up to 55°C, and shelf lives of 14 months have been shown.Oral administration works better when an antacid is included, as this increases the number of phages surviving passage through the stomach.
Topical administration often involves application to gauzes that are laid on the area to be treated.Other forms of administration can include application in liquid form. These vials are usually best kept refrigerated.
The lytic bacteriophages available for phage therapy are best kept refrigerated but discarded if the pale yellow clear liquid goes cloudy.
Phage therapy is generally considered safe.
As with antibiotic therapy and other methods of countering bacterial infections, endotoxins are released by the bacteria as they are destroyed within the patient (Herxheimer reaction). This can cause symptoms of fever.
Care has to be taken in manufacture that the phage medium is free of bacterial fragments and endotoxins from the production process.
Monomicrobic Infection caused by one Bacterium
For example: a Mix of 3 lytic Phages for Bacterium A
Phage 1
Phage 2
Phage 3
Phage Receptor Types and Receptors Number (?) on the cell wall, example for 3 Phages
(3 different Receptors):Receptor 1(X?), Receptor 2(Y?), Receptor 3(Z?)
Rate of Mutation to Resistance to Phages:Phage 1(10^-7), Phage 2(10^-7), Phage 3(10^-7)
Rate of Mutation to Resistance to all lytic Phages for Bacterium A:
(10^-7)*(10^-7)*(10^-7)=10^-21
When, for example, a priori we suspect an Infection caused by 3 different Bacteria: Bacterium A, Bacterium B, Bacterium C
For example: a Mix of 6 (or 9) lytic Phages (2 or 3 Phages for each bacterium):
For Bacterium A
Phage A1
Phage A2
For Bacterium B
Phage B1
Phage B2
For Bacterium C
Phage C1
Phage C2
Phage Receptor Types and Receptors Number (?) on the cell wall, example for 6 Phages (2 different Receptors for each bacterium ):
Bacterium A
Receptor A1(X1?)
Receptor A2(X2?)
Bacterium B
Receptor B1(Y1?)
Receptor B2(Y2?)
Bacterium C
Receptor C1(Z1?)
Receptor C2(Z2?)
Rate of Mutation to Resistance to lytic Phages for each bacterium:
Bacterium A
Phage A1 (10^-7)
Phage A2 (10^-7)
Bacterium B
Phage B1 (10^-7)
Phage B2 (10^-7)
Bacterium C
Phage C1 (10^-7)
Phage C2 (10^-7)
Rate of Mutation to Resistance to lytic Phages:
Bacterium A =(10^-7)*(10^-7)= 10^-14
Bacterium B =(10^-7)*(10^-7)= 10^-14
Bacterium C =(10^-7)*(10^-7)= 10^-14
