Abstract
Summary
Coagulase-negative staphylococci, including S. epidermidis, have emerged as the leading pathogens of hospital-acquired biomaterial-related infections. These infections can be clinically indolent and challenging also for diagnostic imaging. In the current model of catheter-related infections, 68Ga-labeled Siglec-9 PET/CT imaging was able to detect peri-implant S. epidermidis bone infections.
Introduction
Coagulase-negative staphylococci, including S. epidermidis, have emerged as the leading pathogen of nosocomial (hospital-acquired) biomaterial-related infections, including periprosthetic infections and intravascular catheter-related bloodstream infections. Pathogenic S. epidermidis strains exhibit robust attachment to implant surfaces and subsequent biofilm formation. By nature, the clinical picture of periprosthetic S. epidermidis infections can be indolent with vague signs of infection. These infections are also highly challenging for diagnostic imaging and microbiologic studies. Our recent experimental study of 18F-FDG-PET/CT confirmed that subacute peri-implant S. epidermidis infections, reflecting limited inflammatory reaction, are characterised by low 18F-FDG uptake. Vascular adhesion protein-1 (VAP-1) is an inflammation inducible endothelial protein, which controls leukocyte migration to sites of inflammation and infection. Siglec-9 is a leukocyte ligand of VAP-1. We hypothesised that 68Ga-labeled Siglec-9, developed for PET imaging of inflammation and cancer, could be a novel tracer also for early defection of S. epidermidis peri-implant bone infections.
Material & Methods
Thirty adult male Sprague-Dawley rats were randomised into three groups (n=10/group). A clinical intravenous polymer catheter was introduced into the medullary cavity of the left tibia followed by injections of a clinical isolate of S. epidermidis (T-54580, 3 × 108 CFU/mL) and an adjunct sodium morrhuate. In the positive control group, a clinical isolate of S. aureus (52/52A/80, 3 × 105 CFU/mL) with sodium morrhuate was injected. In the negative control group, equal amount of sterile saline was injected via the catheter. The catheter, cut at the level of tibial tuberosity, was left in situ to serve as the implant. Two weeks after surgery, PET imaging with 68Ga-DOTA-Siglec-9 was performed with quantitative analysis of the standardised uptake value (SUV) in the region of interests both in vivo and ex vivo. SUV ratio between the operated and contralateral intact tibia was calculated. The presence of infections and the absence of contamination in the negative control group were verified by separate microbiological analyses of bone samples and retrieved implants. The presence of microbial biofilms on catheters was verified ex vivo with fluorescence microscope. Histologic inflammatory reaction was graded using a scoring system. Intergroup differences were tested by means of ANOVA with a post-hoc test.
Results
Both staphylococcal strains caused histologically acute osteomyelitic changes. In 68Ga-DOTA-Siglec-9 PET/CT imaging of the negative control group, there was a significant difference (29.5%, p<0.001) in the SUV ratio of the operated and contralateral tibia, demonstrating aseptic inflammatory reaction to catheter implantation. The corresponding SUV ratio values were 58.1% in the S. epidermidis group and 41.7% in the S. aureus group. The uptake in the S. epidermidis group was significantly (p=0.009) higher than in the negative control group.
Discussion/Conclusion
The animal model was reproducible in creation of culture-positive biomaterial-related infections. 68Ga-labeled Siglec-9 PET/CT imaging was able to demonstrate aseptic inflammation in the negative control group and the tracer also detected peri-implant bone infections caused by S. epidermidis.
