New developments and future challenges in prevention, diagnosis, and treatment of prosthetic joint infection

Abstract

Prosthetic joint infection (PJI) is a devastating complication that results in substantial costs to society and patient morbidity. Advancements in our knowledge of this condition have focused on prevention, diagnosis, and treatment, in order to reduce rates of PJI and improve patient outcomes. Preventive measures such as optimization of patient comorbidities, and perioperative antibiotic usage are intensive areas of current clinical research to reduce the rate of PJI. Improved diagnostic tests such as synovial fluid (SF) α‐defensin enzyme‐linked immunosorbent assay, and nucleic acid‐based tests for serum, SF, and tissue cultures, have improved diagnostic accuracy and organism identification. Increasing the diversity of available antibiotic therapy, immunotherapy, and alternative implant coatings remain promising treatments to improve infection eradication in the setting of PJI.

IsdB antibody–mediated sepsis following S. aureus surgical site infection

“…While this work has identified the autolysin antigens as potential targets (27,(41)(42)(43), it also identified IsdB as the most immunodominant antigen (17). Our clinical research approach has been focused on elucidating the immune proteome against S. aureus in patients with MSKI and correlating their humoral immunity with their clinical outcome (16,17,(19)(20)(21)(44)(45)(46). While this work also found autolysin antigens to have human vaccine potential, we also found a clear signal that humoral immunity against IsdB is associated with poor clinical outcomes, including amputation and septic death (16,17,20).…”

Bone infection: a clinical priority for clinicians, scientists and educators

“…While vaccines are the most cost-effective intervention for infectious diseases, to date, all efforts to develop an immunisation against S. aureus have failed for various reasons (Proctor, 2015). The main challenges include lack of knowledge of protective versus antibody-dependent bacterial infection enhancement and the great variability in patient-specific immune responses, which are biased by prior exposures to this commensal Ricciardi et al, 2020b). With this knowledge, TF Moriarty et al…”

“…With the introduction of MALDI-TOF MS into microbiological diagnostic laboratories about a decade ago, rapid identification of pathogens to the species level from microbial cultures became possible within a few minutes (Bizzini et al, 2011;Borens et al, 2012). For identifying microbial species directly out of liquid culture, MALDI-TOF MS workflows are already regularly used for blood culture specimens [reviewed in Morgenthaler and Kostrzewa (2015) and Ruiz-Aragon et al (2017)] containing a variable degree of host cellular remnants. This has recently been adapted to joint specimens taken during surgery (Kuo et al, 2020;Noll et al, 2020).…”

“…Blood-based diagnostics have clear advantages over culture, as they are minimally invasive, less time consuming and easy to administer. Unfortunately, existing diagnostics such as CRP, ESR and WBC are not specific and force clinicians to administer empiric antibiotics until the pathogen is identified in culture (Ricciardi et al, 2020a). To overcome this, the potential of anti-S. aureus antibody levels in serum was investigated (Fig.…”

The Rationale for Using Bacteriophage to Treat and Prevent Periprosthetic Joint Infections

“…The minimal inhibitory concentration (MIC) of an antibiotic is determined on cultured bacteria and does not reflect the susceptibility of the bacteria within a biofilm. Killing the bacteria within a biofilm requires a many-fold higher concentration of antibiotic to achieve the minimum biofilm eradication concentration (MBEC) ( Ricciardi et al, 2020 ). Thus, the use of suboptimal antibiotic concentrations could lead to antibiotic resistance in the setting of PJI.…”