AUTHOR=Alt Volker , Gessner André , Merabishvili Maya , Hitzenbichler Florian , Mannala Gopala Krishna , Peterhoff David , Walter Nike , Pirnay Jean-Paul , Hiergeist Andreas , Rupp Markus 

TITLE=Case report: Local bacteriophage therapy for fracture-related infection with polymicrobial multi-resistant bacteria: hydrogel application and postoperative phage analysis through metagenomic sequencing

JOURNAL=Frontiers in Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1428432

DOI=10.3389/fmed.2024.1428432

ISSN=2296-858X

ABSTRACT=Fracture-related infections can be challenging, particularly with concomitant severe bone defects and multi-resistant microorganisms. Wepresent a case of a 42-year-old patient with a fracture-related infection following a war injury from a gunshot with a 12 cm subtrochanteric segmental bone defect and the detection of four different multi-resistant Gram-negative bacteria. Due to antibiotic drug-resistance, treatment with bacteriophages was considered. Phage susceptibility testing revealed activity of a commercially available bacteriophage cocktail (Intesti bacteriophage, Eliava Institute, Tiflisi, Georgia). This phage cocktail was included into a modified two-stage Masquelet technique. During the first intervention, the bone was debrided and samples for microbiological and phage testing harvested. The indwelling intramedullary rod was removed and the bone defect was filled with a PMMA spacer loaded with colistin and bone stabilized with a plate. During the second procedure, the PMMA spacer was removed and a silver coated angular stable plate implanted. The bone defect was filled with a fibular autograft and allograft cancellous bone chips. At the end of the procedure, the Intesti bacteriophage cocktail was injected into a DAC hydrogel and this bacteriophage hydrogel composite was then put on to the angular stable plate. Postoperatively the wound fluid was collected over 72 h and high throughput metagenomic sequencing was performed. This showed a time dependent release of the bacteriophages in the wound fluid with a relatively high concentration after 12 h and decreasing to DNA copies of 0 after 72 h. Further, we have assessed the release of phages from DAC gel and DAC gel effect on the phages in vitro. The results showed a stable and rapid release of phages from the DAC gel (~1x103 PFU/ml). The clinical course of the patient showed no relapse of the infection with good bone consolidation of the bone defect after one year without the need of any surgical revision. 
To our best knowledge this is the first case that shows detection of bacteriophage DNA copies by high throughput metagenomics sequencing in a patient with a complex fracture-related infection. Successful treatment of this case encourages further investigation of bacteriophage therapy in patients with complex bone and joint infections.