Optimization of bacteriophage therapy for difficult-to-treat musculoskeletal infections: a bench-to-bedside perspective.
Laura Bessems, Baixing Chen, Saartje Uyttebroek, David Devolder, C��dric Lood, Stefaan Verwimp, Paul De Munter, Yves Debaveye, Melissa Depypere, Isabel Spriet, Laura Van Gerven, Lieven Dupont, Jeroen Wagemans, Vera van Noort, Rob Lavigne, Willem-Jan Metsemakers, Jolien Onsea
Author Information
Laura Bessems: Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Baixing Chen: Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Saartje Uyttebroek: Department of Neurosciences, Experimental Otorhinolaryngology, Rhinology Research, KU Leuven, Leuven, Belgium.
David Devolder: Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.
C��dric Lood: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
Stefaan Verwimp: Center of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.
Paul De Munter: Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Yves Debaveye: Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.
Melissa Depypere: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Isabel Spriet: Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.
Laura Van Gerven: Department of Neurosciences, Experimental Otorhinolaryngology, Rhinology Research, KU Leuven, Leuven, Belgium.
Lieven Dupont: Department of Pneumology, University Hospitals Leuven, Leuven, Belgium.
Jeroen Wagemans: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
Vera van Noort: Center of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.
Rob Lavigne: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
Willem-Jan Metsemakers: Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Jolien Onsea: Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections.
