Table 4.
Single phage | Pre-made cocktails | Custom cocktails | ||||
---|---|---|---|---|---|---|
Untyped infections | Typed infections | Single species typed infections | Multi-strain typed infections | Polymicrobial typed infections | ||
Phage selection | • One phage with high efficacy against a typed bacterial strain. | • Multiple phages targeting an untyped infection. | • Multiple phages, compromising between efficacy and host range. | • Multiple phages targeting a single typed bacterial strain. | • Multiple phages targeting multiple typed bacterial strains. | • Multiple phages targeting multiple typed bacterial species. |
Aim | • Treat MDR/XDR strains only. | • Treat bacterial infections based on symptoms. | • Treat infections caused by multiple strains of the same species. | • Treat patient specific infections caused by a single typed species. | • Treat multiple strains of the same species in a single patient. | • Treat typed polymicrobial infections in a single patient. |
Advantages | • Easy to change phages. • Easy analysis. |
• Easy recruitment to trials. | • Easy recruitment to trials. • Only limited phage library needed. |
• Predicted high efficacy. • Avoids emerging bacterial resistance. |
• Wide application. | • Wide application. |
Disadvantages | • New phages require additional trials. • Unpredictable results. |
• Poor patient recovery rate. • Unpredictable results. • New formulation means new trial. |
• Cocktail obsolescence. • New formulation means new trial. |
• Unique cocktails increase recruitment difficulty to trials. • Cocktail obsolescence. • Large phage library needed. |
• Every cocktail unique, more difficult to recruit trial participants. • Necessary to reformulate cocktail as new strains appear. • Large phage library needed. |
• Every cocktail unique, more difficult to recruit trial participants. • Necessary to reformulate cocktail as new strains appear. • Multiple large phage libraries needed. |
Iteration | • Phage is discarded or formulation changed as new data emerges. | • Non-effective or hazardous phages are removed as data emerges. • Additional phase I testing if there is poor efficacy or immunogenicity. |
• Non-effective or hazardous phages are removed as data emerges. • Additional phase I testing if there is poor efficacy or immunogenicity. |
• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity. |
• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity. |
• Cocktail composition altered as data on phages emerge. • Additional phase I testing if there is poor efficacy or immunogenicity. |
Design | Single site long term or multi-site short term | Single site long term or multi-site short term | Single site long term or multi-site short term | Multi-site long term | Multi-site long term | Multi-site long term |
Implementation time | + | + | + | ++ or +++* | ++ or +++ | +++ |
Cost | $ | $$ | $$ | $$$ | $$$ | $$$ |
Time to implementation would be affected by the form of treatment chosen. Pre-approved libraries could be implemented faster should suitable criteria be developed.