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PERSPECTIVE article

Front. Cell. Infect. Microbiol.
Sec. Clinical Microbiology
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1434397

Optimization of bacteriophage therapy for difficult-to-treat musculoskeletal infections: a bench-to-bedside perspective

Provisionally accepted
Laura Bessems Laura Bessems 1,2Baixing Chen Baixing Chen 1,2Saartje Uyttebroek Saartje Uyttebroek 3,4David Devolder David Devolder 5Cédric Lood Cédric Lood 6,7Stefaan Verwimp Stefaan Verwimp 7Paul De Munter Paul De Munter 8,9Yves Debaveye Yves Debaveye 10Melissa Depypere Melissa Depypere 11,12Isabel Spriet Isabel Spriet 13,5Laura Van Gerven Laura Van Gerven 14,3,4Lieven Dupont Lieven Dupont 15,16Jeroen Wagemans Jeroen Wagemans 6Vera van Noort Vera van Noort 17,7Rob Lavigne Rob Lavigne 6Willem-Jan Metsemakers, MD, PhD Willem-Jan Metsemakers, MD, PhD 1,2Jolien Onsea Jolien Onsea 1,2*
  • 1 Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium
  • 2 Department of Traumatology, University Hospitals Leuven, Leuven, Brussels, Belgium
  • 3 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Brussels, Belgium
  • 4 Department of Neurosciences, Experimental Otorhinolaryngology, Rhinology Research, KU Leuven, Leuven, Belgium
  • 5 Pharmacy Department, University Hospitals Leuven, Leuven, Belgium
  • 6 Department of Biosystems, Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
  • 7 Center of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium
  • 8 Department of General Internal Medicine, University Hospitals Leuven, Leuven, Brussels, Belgium
  • 9 Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
  • 10 Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Brussels, Belgium
  • 11 Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Brussels, Belgium
  • 12 Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
  • 13 Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Leuven, Belgium
  • 14 Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium
  • 15 Department of Pneumology, University Hospitals Leuven, Leuven, Belgium
  • 16 Department of Chronic Diseases and Metabolism, Respiratory Diseases and Thoracic Surgery, KU Leuven, Leuven, Belgium
  • 17 Institute of Biology, Leiden University, Leiden, Netherlands

The final, formatted version of the article will be published soon.

    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.

    Keywords: Bacteriophages, Bacteriophage therapy, treatment optimization, Bench-to-bedside, Musculoskeletal infections

    Received: 18 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Bessems, Chen, Uyttebroek, Devolder, Lood, Verwimp, De Munter, Debaveye, Depypere, Spriet, Van Gerven, Dupont, Wagemans, van Noort, Lavigne, Metsemakers, MD, PhD and Onsea. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jolien Onsea, Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.