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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 27 - 27
24 Nov 2023
Chen B Chittò M Benavente LP Post V Moreno MG Zeiter S Trampuz A Wagemans J Lavigne R Onsea J Metsemakers W Moriarty F
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Aim

Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA.

Method

Two evolved bacteriophages (MRSA-R14 and COL-R23) with improved antibiofilm activity against a clinical isolate (MRSA3) were tested in combination with vancomycin and a carboxymethylcellulose (CMC) hydrogel in vitro and in vivo. MRSA3 bacterial biofilms were formed on sterile 4 mm sintered porous glass beads at 37 °C for 24 h. Biofilms were exposed to i-phage cocktail (107 PFU/ml), ii-vancomycin at concentrations of 0.5, 1, 10 and 100 times the MIC, or iii-combination of phage cocktail and vancomycin. Recovered biofilm cells, were quantified by colony counting. The stability and release profiles of phage cocktail and vancomycin in co-delivery hydrogel were assessed in vitro for 8 days and 72 hrs, respectively, and subsequently tested in the treatment of 5-day-old MRSA3 infection of a femoral plate osteotomy in mice.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 59 - 59
11 Apr 2023
Chitto M Chen B Kunisch F Wychowaniec J Onsea J Post V Richards G Zeiter S Wagemans J Trampuz A D'Este M Moreno M Lavigne R Moriarty F
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Fracture related infection remains a major challenge in musculoskeletal trauma surgery. Despite best practice, treatment strategies suffer from high failure rates due to antibiotic resistance and tolerance. Bacteriophages represent a promising alternative as they retain activity against such bacteria. However, optimal phage administration protocols remain unknown, although injectable hydrogels, loaded with phage and conventional antibiotics, may support conventional therapy.

In this study we tested the activity of meropenem, and two newly isolated bacteriophages (ϕ9 and ϕ3) embedded within alginate-chitosan microbeads and a hydrogel. Antibiotic and phage stability and activity were monitored in vitro, over a period of 10 days. In vivo, the same material was tested in treatment of a 5-day old Pseudomonas aeruginosa infection of a tibial plate osteotomy in mice. Treatment involved debridement and 5 days of systemic antibiotic therapy plus: i- saline, ii-phages in saline, iii-phages and antibiotics loaded into a hydrogel (n=7 mice/group). To assess the efficacy of the treatments, the infection load was monitored during revision surgery with debridement of the infected tissue after 5,10 and 13 days (euthanasia) by CFU and PFU quantification.

In vitro testing confirmed that the stability of meropenem and activity of ϕ9 and ϕ3, was not affected within the alginate beads or hydrogel over 10 days. The in vivo study showed that all mice receiving phages and antibiotics loaded into a hydrogel survived the infection with a reduction of the bacterial load in the soft tissue. Active phages could be recovered from the infected site at euthanasia (104 PFU/g).

The hydrogel loaded with bacteriophages and meropenem showed a positive result in locally reducing the infection load indicating a synergistic effect of the selected antimicrobials. Overall, our new strategy shows encouraging results for improving the treatment of antibiotic-resistant biofilm infections that are related to medical implants.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 65 - 65
1 Dec 2017
Post V Morgenstern M Harris L Mageiros L Hitchings MD Méric G Pascoe B Sheppard SK Richards G Moriarty F
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Aim

Staphylococcus epidermidis has emerged as an important opportunistic pathogen causing orthopedic device-related infections (ODRIs). In this prospective clinical and laboratory study, we have investigated the association of genome variation and phenotypic features of the infecting S. epidermidis isolate with the clinical outcome of the infected patient.

Method

One hundred and four invasive S. epidermidis isolates were prospectively collected from patients with ODRI. Upon patient entry into the study, surgical parameters such as type of implant; open or closed fracture were documented. Personal characteristics were also documented and included: gender; age; body mass index (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic immunosuppressive conditions. Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up. The clinical outcome after treatment was measured with a mean follow-up period (FUP) of 26 months, and each patient was then considered to have been “cured” or “not cured”. The isolates were tested for their antibiotic susceptibility and ability to form biofilm. Whole genome sequencing was performed on all isolates and genomic variation was related to features associated with “cured” and “not cured”.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 84 - 84
1 Dec 2016
Wahl P Post V Richards G Moriarty F
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Aim

Determine the time concentration profile required to achieve vancomycin-mediated eradication of Staphylococcus aureus biofilm. This is critical for the identification of performance targets for local antibiotic delivery, yet has not been described.

Method

Mature S. aureus UAMS-1 biofilms were grown on titanium-aluminum-niobium discs in Mueller Hinton broth (MHB). After 7 days, the discs were incubated in MHB containing vancomycin at 100, 200, 500, 1′000 and 2′000 mg/L. Both static and shaking conditions were tested. Samples were retrieved at intervals for up to 28 days for quantification of residual biofilm by sonication and serial dilution plating. One additional disc was processed per time point for scanning electron microscopy.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 283 - 283
1 Jul 2014
Post V Wahl P Uckay I Zimmerli W Corvec S Loiez C Ochsner P Moriarty F
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Summary

Staphylococcus aureus isolates from Fracture fixation device related infections contained fewer isolates that form a strong biofilm in comparison with isolates from Prosthetic joint infections. Both orthopaedic implant related infection groups possessed fnbB and sdrE more frequently than the non-implant related infection groups.

Introduction

One of the most common pathogen causing musculoskeletal infections is Staphylococcus aureus. The aim was to characterise S. aureus isolated from these infections and to look for differences between the isolates from orthopaedic implant related infections (OIRI) and those in non-implant related infections (NIRI). The OIRI are further differentiated in those associated with fracture fixation (FFI) devices and those found in prosthetic joint infections (PJI).