Emerging Concepts in Periprosthetic Joint Infection Research: Infection Recurrence and Microbe Persistence

Recurrent periprosthetic joint infection (PJI) is a highly morbid complication following total joint arthroplasty. Despite appropriate medical and surgical management with targeted antimicrobial therapies, many patients who suffer from a PJI experience clinically relevant episodes of recurrence. Though the majority of these recurrent infections are due to microbes that are different from the species initially isolated at the index infection, approximately 15 to 50% of subsequent PJIs are attributed to recurrence with the same causative organism. Treatment resistance, contamination during revision surgery, hematogenous spread of bacteria from a distant source, and the presence of resilient biofilms have long been implicated in these recurrent infections. However, recent preclinical and clinical evidence has demonstrated that certain organisms that commonly cause PJI, namely staphylococcal species, can undergo phenotypic transformation into viable, but nonculturable and quasi-dormant small colony variant forms that may persist intracellularly and lead to recurrent infection. Moreover, some organisms are known to infiltrate the osteocyte lacuno-canalicular network and invade eukaryotic cells to avoid targeting by the host immune system and antimicrobial agents. In doing so, they create microbial reservoirs that may be capable of reactivating to cause symptomatic infection locally or after being transported to the joint by circulating phagocytic cells. Commensal species present in the human microbiome may also become pathogenic and lead to recurrent PJI. Evidence suggests dysbiosis, a pathological imbalance in the composition and function of the microbiome, may induce the translocation of resident organisms from the gut into the bloodstream. Recent studies have also identified joint microbiota signatures that vary in accordance with the presence or absence of certain pathologies, including PJI. CLINICAL RELEVANCE: These processes offer compelling explanations for recurrent infection, particularly when episodes of recurrence do not present in ways that are consistent with hematogenous spread or biofilm persistence. Furthermore, they challenge the notion that all infections can be eradicated, instead suggesting that treatment strategies should aim to achieve homeostatic control in order to prevent symptomatic relapse.