Phages destined for clinical application | Effective against target pathogen |
Well characterised (WGS), without antibiotic resistance genes and virulence factors | |
Non-lysogenic/transducing | |
Propagated on well-characterised bacterial strains | |
Phage preparations | Ideally produced according to GMP standards |
Sterile and free from nonproduct phages | |
Endotoxin level <5 EU·kg·h−2 for i.v. injections | |
Ensured stability along production line | |
Candidate patient selection | Bacterial infections refractory to antibiotics |
Allergy/intolerance to antibiotics | |
Progressive loss of function of involved organ | |
Discussion with the patient regarding the experimental nature of phage therapy and the potential risks and benefits | |
Route of administration | Type and severity of infection |
Inhaled administration: stability testing with nebuliser | |
Phage concentration | Highest safe and tolerated dose below endotoxin limits |
Duration of therapy | Usually guided by clinical course |
Antibiotic therapy | Usually maintained in compassionate use |
Consider testing for phage-antibiotic synergy/antagonism | |
Monitoring | Close clinical and laboratory monitoring |
Systematic documentation of adverse events | |
Serial phage susceptibility testing of bacterial isolates (emergence of phage resistance) | |
Consider phage neutralisation assay in case of no improvement | |
Consider phage pharmacokinetics to guide dosing |
EU: endotoxin units; GMP: Good Manufacturing Practices; i.v.: intravenous; WGS: whole-genome sequencing.