Animal models of hematogenous Staphylococcus aureus osteomyelitis in long bones: a review

Johansen, Louise Kruse; Jensen, Henrik Elvang

doi:10.2147/orr.s45617

Cited by 8 publications

(18 citation statements)

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“…Due to high levels of IL-6 or polymorphic bax gene expression, PMN may have prolonged lifespan in OM [ 22 ] and can therefore become a significant source of oxidants in circulation. Acting together with local factors, such as decreased blood flow, thrombosis, hypoxia, and expression of inducible cyclooxygenase [ 23 ], PMN may enhance the formation of oxidants in inflamed bone tissue.…”

Section: Discussionmentioning

confidence: 99%

Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Grbić¹,

Mirić²,

Kisic³

et al. 2014

Mediators of Inflammation

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In bacterial bone infections, excessively formed oxidants may result in local and systemic oxidative stress. Vitamin C is the major extracellular nonenzymatic antioxidant, also implicated in bone cells metabolism and viability. The physiological functions of vitamin C largely depend on its redox status. We sequentially assessed oxidative stress markers, hydroperoxides and malondialdehyde (MDA), total antioxidant activity (AOA), total vitamin C, ascorbic acid (Asc), and oxidized/reduced vitamin C ratio in 137 patients with acute osteomyelitis (OM). Compared to 52 healthy controls, in OM group baseline serum hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc and AOA were lower (P < 0.05, resp.). On the other side, total vitamin C levels in patients and controls were similar (P > 0.05), thereby suggesting a relative rather than absolute vitamin C deficiency in OM. During the follow-up, oxidative stress markers, AOA, and oxidizedreduced vitamin C ratio were gradually returned to normal, while there was no apparent change of total vitamin C concentrations. Persistently high values of oxidized/reduced vitamin C ratio and serum MDA were found in subacute OM. In conclusion, acute OM was associated with enhanced systemic oxidative stress and the shift of vitamin C redox status towards oxidized forms.

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Section: Discussionmentioning

confidence: 99%

Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Grbić¹,

Mirić²,

Kisic³

et al. 2014

Mediators of Inflammation

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“…Hematogenous osteomyelitis is a disease primarily found in children but is also associated with implants inserted in environmentally sterile conditions, such as those for total joint arthroplasties and fracture fixation of closed fractures. Hematogenous osteomyelitis in children is thought to be caused by the anatomy of the metaphyseal region of the long bone [ 2 ]. The vascular loop structure within growing long bones slows the blood flow through the region, localizing bacteria that may be in the blood.…”

Section: Introductionmentioning

confidence: 99%

“…The vascular loop structure within growing long bones slows the blood flow through the region, localizing bacteria that may be in the blood. The disease presents as bacterial abscesses forming adjacent to the physis in the metaphyseal region of the bone, where bacteria can accumulate in the capillary beds (sinuses) [ 2 ]. Animal models for hematogenous osteomyelitis in children involve inoculation of bacteria, from a strain known to cause osteomyeltitis, into the bloodstream, often with the use of a sclerosing agent, such as sodium morrhuate, to entrap the bacteria in the blood vessels of the metaphysis of the bone and promote bacteria propagation [ 3 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a hematogenous implant-related infection in a rat model

Shiels

Bedigrew

Wenke

2015

BMC Musculoskelet Disord

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BackgroundImplant-related osteomyelitis is a major complication that requires immediate treatment, often involving removal of the implant, prolonging patient recovery and inflating expenses. Current research involving interventions to diminish the prevalence of such measures include investigating prophylactic and therapeutic remedies. A proper and accurate animal model is needed to thoroughly investigate such treatments. The scope of this project was to develop an animal model in which a consistent and measurable infection can be formed on an orthopedic implant when bacteria is introduced via a hematogenous source.MethodsTitanium Kirschner-wires were implanted into the intramedullary canals of both femurs. Staphylococcus aureus, ranging from104 to 109 colony forming units, was injected into a tail vessel. After a designated time (3, 7, 14, or 42 days) the femurs were harvested and bacterial numbers determined for both the femur and the implanted K-wire. In addition, histology and micro-computed tomography were used as subjective tools to further characterize the infection.ResultsConsistent infection, that is infection of ≥75 % of the femurs, wasn’t achieved until 107 CFU S. aureus was injected. At 107 CFU, the femurs contained 4.6x106 CFU/g bone tissue at day 3 and 4.8×108 CFU/g bone tissue by day 14. The wire showed comparable contamination with 4.8×104 CFU/mm2 at day 3 and 3.7×105/mm2 by day 14. After 42 days, the bacteria number decreased but was still occupying at 1.9×105 CFU/g bone tissue. There were morphological changes to the bone as well. At day 42, there were signs of osteonecrosis and active bone formation when compared to control animals that received a K-wire but were inoculated with saline.ConclusionsA model for hematogenous osteomyelitis, a common complication associated with implants, has been introduced. A reproducible, preclinical model is essential to evaluate future methods used to mitigate blood-borne bacteria hardware and bone infections.

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“…Johansen and Jensen have reviewed the haematogenously spread S. aureus OM in animal models [ 20 ]. This group and others have noticed a similarity to children where OM most often involve the growth zones of the long bones of the lower extremities, perhaps due to more exposure of the long bones of the extremities to small blunt trauma from childhood activities, especially of boys, creating a locus of minor necrosis [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Twenty clinically healthy, specific pathogen-free Danish Landrace-Yorkshire crossbreed female pigs aged 8–12 weeks were purchased from local commercial pig farmers. After 1 week of acclimatization, the pigs were, under propofol anaesthesia, inoculated with a suspension of a porcine strain of S. aureus (S54F9) (10 4 –10 5 colony forming units (CFU) per kilogram body weight (BW) in 1.0 to 1.5 mL saline) into the femoral artery of the right hind limb simulating haematogenously spread OM in children and avoiding reactive changes induced by the trauma of directly inoculating in a peripheral bone, as described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT —the inference from a juvenile porcine model

et al. 2019

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PurposeTo examine parameters affecting the detection of osteomyelitis (OM) by [18F]FDG PET/CT and to reduce tracer activity in a pig model.Background[18F]FDG PET/CT is recommended for the diagnosis of OM in the axial skeleton of adults. In children, OM has a tendency to become chronic or recurrent, especially in low-income countries. Early diagnosis and initiation of therapy are therefore essential. We have previously demonstrated that [18F]FDG PET/CT is promising in juvenile Staphylococcus aureus (S. aureus) OM of peripheral bones in a pig model, not failing even small lesions. When using imaging in children, radiation exposure should be balanced against fast diagnostics in the individual case.MethodsTwenty juvenile pigs were inoculated with S. aureus. One week after inoculation, the pigs were [18F]FDG PET/CT scanned. PET list-mode acquired data of a subgroup were retrospectively processed in order to simulate and examine the image quality obtainable with an injected activity of 132 MBq, 44 MBq, 13.2 MBq, and 4.4 MBq, respectively.ResultsAll lesions were detected by [18F]FDG PET and CT. Some lesions were very small (0.01 cm3), and others were larger (4.18 cm3). SUVmax was higher when sequesters (p = 0.023) and fistulas were formed (p < 0.0001). The simulated data demonstrated that it was possible to reduce the activity to 4.4 MBq without compromising image quality in pigs.Conclusions[18F]FDG PET/CT localized even small OM lesions in peripheral bones. It was possible to reduce the injected activity considerably without compromising image quality, impacting the applicability of PET/CT in peripheral OM in children.

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Animal models of hematogenous Staphylococcus aureus osteomyelitis in long bones: a review

Cited by 8 publications

References 81 publications

Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Development of a hematogenous implant-related infection in a rat model

An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT —the inference from a juvenile porcine model

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