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

• Published in: Viruses 2021-09, Vol.13 (10), p.1898
• Main Authors: Van Nieuwenhuyse, Brieuc, Galant, Christine, Brichard, Bénédicte, Docquier, Pierre-Louis, Djebara, Sarah, Pirnay, Jean-Paul, Van der Linden, Dimitri, Merabishvili, Maya, Chatzis, Olga
• Format: Article
• Language: English
• Subjects: Allografts - drug effects; Allografts - microbiology; Anti-Bacterial Agents - pharmacology; antibiotic-bacteriophage combination; Antibiotics; Automation; bacteriophage; Biofilms; Biopsy; Bone and Bones - drug effects; Bone and Bones - microbiology; Bone and Bones - pathology; Bone surgery; Case Report; Catheters; Chemotherapy; Child; Chronic infection; chronic osteitis; Coinfection - therapy; Debridement; Drug Interactions; Female; Humans; Intravenous administration; Lincosamides; Methicillin; Pelvis; phage therapy; Phage Therapy - methods; Phages; Pharmacodynamics; Phenotypes; polymicrobial biofilm; Respiration; Sarcoma; Sarcoma, Ewing - drug therapy; Staphylococcal Infections - diagnosis; Staphylococcal Infections - therapy; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus infections; Staphylococcus Phages - physiology; Streptogramin B; Surgery
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13101898

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 , and was worsened by methicillin-susceptible exhibiting an inducible Macrolides-Lincosamides-Streptogramin B resistance phenotype (iMLSB). After failure of conventional conservative treatment, combination of in situ anti- 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 , or 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.