Use of Phage Therapy for Treatment of a Periprosthetic Joint Infection

At The Ottawa Hospital (TOH), the orthopedic infectious diseases team is currently managing a very challenging case: a 78-year-old female with a severe, chronic-recalcitrant right hip PJI due to a multidrug resistant strain of S. epidermidis in which surgical source control with complete removal of implants cannot be achieved, and in whom there are no viable antibiotic treatment options for chronic suppressive therapy. This patient has undergone multiple surgical revisions with complex reconstructions and adjunctive flap coverage procedures and has received prolonged courses of antibiotic therapy. Unfortunately, this patient suffered multiple, severe antibiotic allergic reactions during initial treatment course which has precluded the use of any viable suppressive therapy - a treatment strategy which is critical to preventing relapse of infection and is at the crux of chronic PJI management. In the absence of any viable adjunctive antimicrobial therapy, this patient is at very high risk of mortality. The Investigators have exhausted all surgical and medical management of PJI for our patient. Remaining on lower dose daptomycin and adjunctive oral rifampin, the patient continued to experience myalgias and neuropathy. It was anticipated that with eventual discontinuation of daptomycin (this patient cannot remain indefinitely on this therapy given her symptoms), her infection would again rapidly relapse with systemic symptoms. This infection is associated with a high risk of mortality without a viable suppressive antimicrobial treatment; a more aggressive surgical approach (high right leg amputation and hemipelvectomy) to reduce the burden of infection is not possible in this patient given her frailty, co-morbidity, resultant significant physical debility and risk of surgical complications. Given the above, phage therapy poses very low risk and is a remaining possible medical therapy that may eradicate her infection. The primary objective of this study is to investigate the safety, tolerability and activity or efficacy of systemic (intravenous) and intra-articular administration of phage in our patient with chronic-recalcitrant methicillin-resistant S. epidermidis PJI. Secondary objectives will be documenting clinical changes pre- and post-therapy, as well as identifying adjunctive changes in biomarkers (C-reactive protein \[CRP\], erythrocyte sedimentation rate \[ESR\], and interleukin-6 \[IL-6\]) correlated with PJI. In this study, lytic phage prepared in injection-grade saline will be administered to the patient both intravenously and intraarticularly, twice a day for a duration of 14 days. In addition to phage therapy, the patient will receive standard of care antibiotic therapy. The patient will remain in clinical follow-up for up to one year.