| Autor: |
Würstle S; Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, 81675 Munich, Germany ., Stender J; Bundeswehr Institute of Microbiology, 80937 Munich, Germany., Hammerl JA; Unit Epidemiology, Zoonoses and Antimicrobial Resistances, Department Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany., Vogele K; Physics of Synthetic Biological Systems-E14, Physics-Department and ZNN, Technical University Munich, 85748 Munich, Germany., Rothe K; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, 81675 Munich, Germany., Willy C; Trauma & Orthopaedic Surgery, Septic & Reconstructive Surgery, Research and Treatment Centre Septic Defect Wounds, Bundeswehr (Military) Academic Hospital Berlin, 10115 Berlin, Germany., Bugert JJ; Bundeswehr Institute of Microbiology, 80937 Munich, Germany. |
| Abstrakt: |
Despite numerous advances in personalized phage therapy, smooth logistics are challenging, particularly for multidrug-resistant Gram-negative bacterial infections requiring high numbers of specific lytic phages. We conducted this study to pave the way for efficient logistics for critically ill patients by (1) closely examining and improving a current pipeline under realistic conditions, (2) offering guidelines for each step, leading to safe and high-quality phage supplies, and (3) providing a tool to evaluate the pipeline's efficiency. Due to varying stipulations for quality and safety in different countries, we focused the pipeline on all steps up to a required phage product by a cell-free extract system. The first of three study runs included patients with respiratory bacterial infections from four intensive care units, and it revealed a cumulative time of up to 23 days. Ultimately, adjustment of specific set points of the vulnerable components of the pipeline, phage isolation, and titration increased the pipeline's efficiency by 15% and decreased the maximum required time to 13 days. We present a site-independent practical approach to establish and optimize pipelines for personalized phage delivery, the co-organization of pipeline components between different institutions, non-binding guidelines for every step, and an efficiency check for phage laboratories. |
