Clinical utilization of species‐specific immunoassays for identification of Staphylococcus aureus and Streptococcus agalactiae in orthopedic infections

Abstract

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture-based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigenspecific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti-S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture-related infection (FRI). Anti-S. aureus and anti-GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species-specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture.

Antibacterial Activity of Electrospun Polyacrylonitrile Copper Nanoparticle Nanofibers on Antibiotic Resistant Pathogens and Methicillin Resistant Staphylococcus aureus (MRSA)

“…The key characteristics of these bacteria species and their related diseases are listed below in Table 3. [86,87] Colonizes the genital tract of some women, causing vertical transmission Neonatal sepsis, meningitis, pneumonia S. pneumoniae [88,89] Respiratory pathogen, some strains have antibiotic resistance Pneumonia, Bacteremia, Meningitis, Otitis Media, Sinusitis K. pneumoniae [90,91] Gram-negative bacterium, respiratory pathogen, urinary tract pathogen, some strains have antibiotic resistance…”

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

“…Further studies have shown that S. aureus also infects living osteocytes and forms small colony variants in this niche in vitro; moreover, infection of osteocytes has also been shown in human patients (Yang et al, 2018). As each osteocyte has approximately 40-50 canaliculi (Beno et al, 2006;Tiede-Lewis et al, 2017), these cells may effectively serve as OLCN "hubs" for continued bacterial invasion to neighbouring and distant osteocytes within bone tissue and may be a key factor in infection persistence.…”

“…Decreased T cell and B cell activation is associated with reduced production of S. aureus-specific IgG (Farnsworth et al, 2018a;Farnsworth et al, 2015). Immuneimpairing hyperinflammation in the obese/T2D host is also linked to other complications of this disease, including liver dysfunction, islet inflammation and gut dysbiosis, which appear to be primarily mediated by obesity (Belkaid and Hand, 2014;Lumeng and Saltiel, 2011;Thingholm et al, 2019). Thus, targeting the causes of inflammation in obese/T2D patients, such as the well-recognised gut dysbiosis, opens promising new avenues for decreasing susceptibility to the more severe implant-associated osteomyelitis and other complications in this disease population.…”

“…As already described, ALBC is still commonly applied as cement beads to a trauma wound or as a moulded cement spacer replacing a prosthetic joint, despite significant uncertainty about antibiotic release and efficacy. Currently, several innovative biomaterials are available as promising alternatives to bone cement for local application of antibiotics targeting bone infections (Foster et al, 2020b;Inzana et al, 2016;Ter Boo et al, 2015). These biodegradable materials eliminate the need for follow-up removal surgeries and often have a more optimal and complete antimicrobial release profile (Inzana et al, 2016;McKee et al, 2010).…”

“…Using these assays developed for serum antibodies to study ASCs, S. aureus-infected patients with multiple types of bone infections, tracked therapy and recurrence were studied (Muthukrishnan et al, 2020;. Additionally, Sulovari et al (2020) achieved reasonable success in simultaneous identification of Streptococcus agalactiae and S. aureus infections in the same immunoassay. However, a critical high priority area of future research is developing immunodiagnostic assays for reliable identification of polymicrobial infections, including S. aureus, S. epidermidis, Streptococcus agalactiae, Cutibacterium acnes and Enterobacteriae.…”