Not much to say about this that I didn’t say in a previous post.
Once again, researchers are claiming to advance the field of phage therapy by using mice as animate test tubes: mice are injected with pathogenic bacteria, followed shortly (or concomitantly) with a dose of phage. The phage kill the bacteria, the mice live, the authors get a publication.
The mice live, that is, unless you wait an hour before administering the phage. Then survival drops to 50%:
The authors, to their credit, do acknowledge that immediate administration of phage therapy upon acquiring an infection, before any symptoms are manifest, might be a tad unrealistic.
They show no awareness however, that their model of bacteremia is also completely unrealistic. There is no primary infection, as is the case in all clinical cases of bacteremia, and the bacteria are present at ridiculously high levels – on the order of 10^7/mL, a concentration that is a million times greater than that found for a typical human bloodstream infection.
Nor do they show any awareness that the phage doses given–up to 10^8/mL of plasma volume–are also unrealistic, exceeding that reported in human case studies to date by a thousand-fold or more.
They seem blissfully unaware that phage efficacy, like any other therapeutic entity, is governed by the laws of second-order kinetics (meaning that the drug and the target have to physically interact and do so more slowly as concentrations are reduced). Instead their dosing regimen is based on MOI (multiplicity of infection, the ratio of phage to bacteria), a parameter that has no relevance outside the confines of a test tube.
Papers like this have been published for decades now. All that changes are the identities of the bugs and the phage. Does anyone really believe this is progress?