Stability of magistral phage preparations before therapeutic application in patients with chronic rhinosinusitis, sepsis, pulmonary, and musculoskeletal infections

Bacteriophages have (re)gained popularity as an adjunct antibacterial therapy. On top of the self-amplifying character of phages, their titer can be influenced by several factors which could lead to reduced titers after preparation and storage. The stability of phage preparations, used for the treatment of chronic rhinosinusitis (CRS), sepsis, pulmonary, and musculoskeletal infections, was investigated. Staphylococcus aureus phage ISP and Pseudomonas aeruginosa phages PNM, 14-1 and PT07 were evaluated. These phages were magistrally prepared by diluting active pharmaceutical products and storing them in different polypropylene/polycarbonate syringes at 4(degrees)C. Titers were monitored for 7-21 days using the double-agar overlay method. For 7 days, titers remained stable. Afterwards, the phage titer reduced for all phages with an average reduction of 0.78 log (P < 0.0001) plaque-forming units (PFUs)/mL after 14 days and 1 log PFU/mL after 21 days (P < 0.0001). PT07 titers dropped below the predefined threshold after 2 days in polycarbonate syringes. In addition, the stability after irrigation using a nasal douche (CRS) and infusion through a catheter (sepsis) was assessed. No changes were observed after using these devices with a mean change in titer of -0.07 log PFU/mL (P = 0.9062) and -0.03 log PFU/mL (P = 0.7350), respectively. In conclusion, a decreased titer after storage of a phage solution can lead to administration of subtherapeutic concentrations. In our experiments, we demonstrated that liquid phage solutions can be stored in syringes at 4 degrees C for 5-7 days. PT07 appeared to be less stable, especially in polycarbonate syringes. Irrigation using a nasal douche or infusion through a catheter does not impact phage titer.