A comparative 18F-FDG PET/CT imaging of experimental Staphylococcus aureus osteomyelitis and Staphylococcus epidermidis foreign-body-associated infection in the rabbit tibia

Abstract

Background: 18F-FDG-PET imaging has emerged as a promising method in the diagnosis of chronic osteomyelitis commonly due to Staphylococcus aureus. The inaccuracy of 18 F-FDG-PET in the detection of periprosthetic joint infections may be related to the predominance of low-virulent S. epidermidis strains as the causative pathogen. We have compared the18F-FDG-PET characteristics of S. aureus osteomyelitis and foreign-body-associated S. epidermidis infections under standardized laboratory conditions.

Methods: Twenty-two rabbits were randomized into three groups. In group 1, a localized osteomyelitis model induced with a clinical strain of S. aureus was applied. In groups 2 and 3, a foreign-body-associated infection model induced with a clinical or laboratory strain of S. epidermidis was applied. A small block of bone cement was surgically introduced into the medullary cavity of the proximal tibia followed by peri-implant injection of S. aureus (1 × 105 CFU/mL) or one of the two S. epidermidis (1 × 109 CFU/mL) strains with an adjunct injection of aqueous sodium morrhuate. In group 1, the cement block was surgically removed at 2 weeks but left in place in groups 2 and 3 in order to mimic foreign-body-associated S. epidermidis infections. At 8 weeks, the animals were imaged using 18 F-FDG PET/CT. The presence of bacterial infection was confirmed by cultures, and the severity of bone infections was graded by means of radiography, peripheral quantitative CT, and semi-quantitative histology.

Results: The S. aureus strain caused constantly culture-positive osteomyelitis. The clinical S. epidermidis strain resulted in foreign-body-associated infections, while the laboratory S. epidermidis strain (ATCC 35983) induced only occasionally culture-positive infections. There was a correlation (r = 0.645; P = 0.013) between semi-quantitative score of leukocyte infiltration and the 18 F-FDG uptake in animals with positive cultures. Standardized uptake value (SUV) of the infected bones was twofold (P < 0.001) in S. aureus animals compared with S. epidermidis animals, but there was only a trend (P = 0.053, ANOVA) in the differences of the corresponding SUV ratios. This was due to the altered 18 F-FDG uptake of the contralateral tibias probably reflecting a systemic impact of severe osteomyelitis.

Conclusion: The peri-implant inoculation of S. epidermidis, reflecting low virulence of the pathogen and limited leukocyte infiltration, was characterized by low 18 F-FDG uptake.

Figures

Figure 1

Transaxial18 F-FDG PET, CT, and combined18F-FDG PET/CT images at the site of induced osteomyelitis. In the three groups of animals with S. aureus (52/52A/80), S. epidermidis (ATCC 35983), or S. epidermidis (T-54580) inoculum. In each animal, the left tibia (on the right) was infected, and the contralateral intact bone (on the left) served as the control.

Figure 2

18F-FDG PET/CT uptake. Bar graphs representing SUV (A) and SUV ratio (B) values (±SD) (n = 6 to 8).

Figure 3

Lateral radiographs of the infected tibias. In animals with S. aureus (52/52A/80) (a), S. epidermidis (ATCC 35983) (b), or S. epidermidis (T-54580) inoculum (c) at 8 weeks. The S. aureus group of animals (a) showed more prominent periosteal reaction, architectural distortion of the metaphyseal cancellous bone, widening of the tibial shaft, and a completely open cortical window (large arrow). The block of bone cement was visible on the radiographs of the S. epidermidis groups of animals (b and c, small arrow). The animals with S. epidermidis (ATCC 35983) inoculum (b) showed partial healing of the cortical defect (large arrow) and minimal changes of the local bone architecture. In animals with S. epidermidis (T-54580) inoculum (c), the cortical window was open and accompanied with periosteal reaction and minor distortion of the surrounding bone architecture.

Figure 4

Cross-sectional histological sections of the infected tibias. In the animals with S. aureus (52/52A/80) (a), S. epidermidis (ATCC 35983) (b), or S. epidermidis (T-54580) inoculum (c) (van Gieson stains). In animals with S. aureus inoculum, drastic osteomyelitic changes is seen characterized by a nearly circumferential periosteal reaction, new bone formation, and sequester formation and infiltration of polymorphonuclear leukocytes with occasional microabscesses. Animals with S. epidermidis (ATCC 35983) inoculum did not show signs of infection. In these animals, closure of cortical defect and only a limited number of inflammatory cell infiltrate was seen. In animals with S. epidermidis (T-54580) inoculum, signs of chronic/subacute osteomyelitis are seen characterized by periosteal reaction with periosteal sclerosis, infiltration of lymphocytes and plasma cells, and bone marrow showing signs of fibrosis.