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Case Report

A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions

by
Brieuc Van Nieuwenhuyse
1,*,
Christine Galant
2,
Bénédicte Brichard
3,
Pierre-Louis Docquier
4,
Sarah Djebara
5,
Jean-Paul Pirnay
6,
Dimitri Van der Linden
7,
Maya Merabishvili
6,† and
Olga Chatzis
7,†
1
Pediatric Department, Institute of Experimental and Clinical Research (IREC/PEDI), Université Catholique de Louvain—UCLouvain, B-1200 Brussels, Belgium
2
Department of Pathology, Institute of Experimental and Clinical Research, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain—UCLouvain, B-1200 Brussels, Belgium
3
Department of Pediatric Haematology, Department of Pediatrics, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain—UCLouvain, B-1200 Brussels, Belgium
4
Department of Orthopedic Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain—UCLouvain, B-1200 Brussels, Belgium
5
Center for Infectious Diseases ID4C, Queen Astrid Military Hospital, B-1120 Brussels, Belgium
6
Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, B-1120 Brussels, Belgium
7
Pediatric Infectious Diseases, General Pediatrics Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain—UCLouvain, B-1200 Brussels, Belgium
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2021, 13(10), 1898; https://doi.org/10.3390/v13101898
Submission received: 4 August 2021 / Revised: 14 September 2021 / Accepted: 16 September 2021 / Published: 22 September 2021
(This article belongs to the Special Issue State-of-the-Art Phage Therapy Development in Europe)
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Abstract

Phage therapy (PT) shows promising potential in managing biofilm infections, which include refractory orthopedic infections. We report the case of a 13-year-old girl who developed chronic polymicrobial biofilm infection of a pelvic bone allograft after Ewing’s sarcoma resection surgery. Chronic infection by Clostridium hathewayi, Proteus mirabilis and Finegoldia magna was worsened by methicillin-susceptible Staphylococcus aureus exhibiting an inducible Macrolides-Lincosamides-Streptogramin B resistance phenotype (iMLSB). After failure of conventional conservative treatment, combination of in situ anti-S. aureus PT with surgical debridement and intravenous antibiotic therapy led to marked clinical and microbiological improvement, yet failed to prevent a recurrence of infection on the midterm. This eventually led to surgical graft replacement. Multiple factors can explain this midterm failure, among which incomplete coverage of the polymicrobial infection by PT. Indeed, no phage therapy against C. hathewayi, P. mirabilis or F. magna could be administered. Phage-antibiotic interactions were investigated using OmniLog® technology. Our results suggest that phage-antibiotic interactions should not be considered “unconditionally synergistic”, and should be assessed on a case-by-case basis. Specific pharmacodynamics of phages and antibiotics might explain these differences. More than two years after final graft replacement, the patient remains cured of her sarcoma and no further infections occurred.
Keywords: phage therapy; bacteriophage; Staphylococcus aureus; chronic osteitis; polymicrobial biofilm; antibiotic-bacteriophage combination; phage-antibiotic interactions; phage-antibiotic synergy phage therapy; bacteriophage; Staphylococcus aureus; chronic osteitis; polymicrobial biofilm; antibiotic-bacteriophage combination; phage-antibiotic interactions; phage-antibiotic synergy

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MDPI and ACS Style

Van Nieuwenhuyse, B.; Galant, C.; Brichard, B.; Docquier, P.-L.; Djebara, S.; Pirnay, J.-P.; Van der Linden, D.; Merabishvili, M.; Chatzis, O. A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions. Viruses 2021, 13, 1898. https://doi.org/10.3390/v13101898

AMA Style

Van Nieuwenhuyse B, Galant C, Brichard B, Docquier P-L, Djebara S, Pirnay J-P, Van der Linden D, Merabishvili M, Chatzis O. A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions. Viruses. 2021; 13(10):1898. https://doi.org/10.3390/v13101898

Chicago/Turabian Style

Van Nieuwenhuyse, Brieuc, Christine Galant, Bénédicte Brichard, Pierre-Louis Docquier, Sarah Djebara, Jean-Paul Pirnay, Dimitri Van der Linden, Maya Merabishvili, and Olga Chatzis. 2021. "A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions" Viruses 13, no. 10: 1898. https://doi.org/10.3390/v13101898

APA Style

Van Nieuwenhuyse, B., Galant, C., Brichard, B., Docquier, P.-L., Djebara, S., Pirnay, J.-P., Van der Linden, D., Merabishvili, M., & Chatzis, O. (2021). A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions. Viruses, 13(10), 1898. https://doi.org/10.3390/v13101898

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