Azad, Marisa

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 109 PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.

SUMMARY Implant-associated infections (IAIs) pose serious threats to patients and can be associated with significant morbidity and mortality. These infections may be difficult to diagnose due, in part, to biofilm formation on device surfaces, and because even when microbes are found, their clinical significance may be unclear. Despite recent advances in laboratory testing, IAIs remain a diagnostic challenge. From a therapeutic standpoint, many IAIs currently require device removal and prolonged courses of antimicrobial therapy to effect a cure. Therefore, making an accurate diagnosis, defining both the presence of infection and the involved microorganisms, is paramount. The sensitivity of standard microbial culture for IAI diagnosis varies depending on the type of IAI, the specimen analyzed, and the culture technique(s) used. Although IAI-specific culture-based diagnostics have been described, the challenge of culture-negative IAIs remains. Given this, molecular assays, including both nucleic acid amplification tests and next-generation sequencing-based assays, have been used. In this review, an overview of these challenging infections is presented, as well as an approach to their diagnosis from a microbiologic perspective.

Periprosthetic joint infection (PJI) following total hip and total knee arthroplasty continues to be a leading cause of re-operation and revision arthroplasty. Not only is the treatment of PJI notoriously challenging, but success rates are variable. Regardless of the surgical strategy used, successful management of PJI requires a comprehensive surgical debridement focused at eradicating the underlying biofilm followed by appropriate antimicrobial therapy. Although systemic antimicrobial delivery continues to be a cornerstone in the treatment of PJI, many surgeons have started using local antibiotics to deliver higher concentrations of antibiotics directly into the vulnerable joint and adjacent soft tissues, which often have compromised vascularity. Available evidence on the use of topical powder, bone cement, and calcium sulphate carriers for local delivery of antibiotics during the initial treatment of PJI is limited to studies that are extremely heterogeneous. There is currently no level-1 evidence to support routinely using these products. Further, appropriately powered, prospective studies are needed to quantify the safety and efficacy of antibiotic-located calcium-sulphate carriers to justify their added costs. These products should not encourage surgeons to deviate from best practice guidelines, such as those recommended during the International Consensus Meeting on Musculoskeletal Infections.

The diagnosis of periprosthetic joint infection (PJI) is challenging, often requiring multiple clinical specimens and diagnostic techniques, some with prolonged result turnaround times. Here, the diagnostic performance of the Investigational Use Only (IUO) BioFire Joint Infection (JI) Panel was compared to 16S rRNA gene-based targeted metagenomic sequencing (tMGS) applied to synovial fluid for PJI diagnosis.

Periprosthetic joint infection (PJI) is a dreadful complication of joint replacement. Noninvasive identification of infectious pathogens has been traditionnally limited to culture-based testing of synovial fluid which has poor sensitivity.

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» Periprosthetic joint infection (PJI) following hip hemiarthroplasty (HA) is a devastating complication, incurring immense health-care costs associated with its treatment and placing considerable burden on patients and their families. These patients often require multiple surgical procedures, extended hospitalization, and prolonged antimicrobial therapy. » Notable risk factors include older age, higher American Society of Anesthesiologists (ASA) score, inadequate antibiotic prophylaxis, non-antibiotic-loaded cementation of the femoral implant, longer duration of the surgical procedure, and postoperative drainage and hematoma. » Although the most frequent infecting organisms are gram-positive cocci such as Staphylococcus aureus , there is a higher proportion of patients with gram-negative and polymicrobial infections after hip HA compared with patients who underwent total hip arthroplasty. » Several surgical strategies exist. Regardless of the preferred surgical treatment, successful management of these infections requires a comprehensive surgical debridement focused on eradicating the biofilm followed by appropriate antibiotic therapy. » A multidisciplinary approach led by surgeons familiar with PJI treatment and infectious disease specialists is recommended for all cases of PJI after hip HA to increase the likelihood of treatment success.