Novel therapeutic interventions towards improved management of septic arthritis

Abstract

Septic arthritis (SA) represents a medical emergency that needs immediate diagnosis and urgent treatment. Despite aggressive treatment and rapid diagnosis of the causative agent, the mortality and lifelong disability, associated with septic arthritis remain high as close to 11%. Moreover, with the rise in drug resistance, the rates of failure of conventional antibiotic therapy have also increased. Among the etiological agents frequently isolated from cases of septic arthritis, Staphylococcus aureus emerges as a dominating pathogen, and to worsen, the rise in methicillin-resistant S. aureus (MRSA) isolates in bone and joint infections is worrisome. MRSA associated cases of septic arthritis exhibit higher mortality, longer hospital stay, and higher treatment failure with poorer clinical outcomes as compared to cases caused by the sensitive strain i.e methicillin-sensitive S. aureus (MSSA).In addition to this, equal or even greater damage is imposed by the exacerbated immune response mounted by the patient’s body in a futile attempt to eradicate the bacteria. The antibiotic therapy may not be sufficient enough to control the progression of damage to the joint involved thus, adding to higher mortality and disability rates despite the prompt and timely start of treatment. This situation implies that efforts and focus towards studying/understanding new strategies for improved management of sepsis arthritis is prudent and worth exploring.The review article aims to give a complete insight into the new therapeutic approaches studied by workers lately in this field. To the best of our knowledge studies highlighting the novel therapeutic strategies against septic arthritis are limited in the literature, although articles on pathogenic mechanism and choice of antibiotics for therapy, current treatment algorithms followed have been discussed by workers in the past. The present study presents and discusses the new alternative approaches, their mechanism of action, proof of concept, and work done so far towards their clinical success. This will surely help to enlighten the researchers with comprehensive knowledge of the new interventions that can be used as an adjunct therapy along with conventional treatment protocol for improved success rates.

Surgery's role in contemporary osteoarticular infection management

“…Even more worryingly, the antigen-induced inflammatory response may persist and continue to damage the joint architecture after the infection has been cleared ( 49 , 50 ). In addition to enzymes from bacteria, white cells, and synovium, the cartilage's own chondrocytes may also play a part in its destruction ( 51 ). An ultrastructural analysis of chondrocytes in experimentally produced septic arthritis showed an increase in lysosomal electron-dense bodies, suggestive of the production of proteolytic enzymes in both the superficial and deep layers of articular cartilage ( 51 ).…”

Periprosthetic joint infection following hip hemiarthroplasty

“… 26 Following bacterial seeding, bacterial products initiate the inflammatory cascade. 27 The subsequent influx of cytokines induces a cascade of events that is responsible for the pathogenesis thought to contribute to destruction of cartilage and joint erosion, 28 a process shown to occur within three days of infection. 27 In addition, recent studies have discovered bacterial colonization of the osteocyte-lacuno canalicular network, a reservoir for bacteria which unquestionably plays an important role in development of osteomyelitis.…”

Septic arthritis in an in vivo murine model induced by Staphylococcus aureus

“…There are other novel and targeted therapies, such as antimicrobial peptides and matrix metalloproteinase-based therapy, with direct bactericidal and immunomodulatory effects that show promising early results. 35 However, they will require further work before they are clinically applicable. In any event, the present work used a Hla-producing and a Hla-deficient strain of S. aureus in an in vivo model, and identified two distinct harmful mechanisms on chondrocyte viability during S. aureus septic arthritis: 1) rapid cell death produced by Hla, and 2) a delayed inflammatory response also resulting in chondrocyte death.…”