<i>Staphylococcus epidermidis</i> is cleared from biomaterial implants but persists in peri‐implant tissue in mice despite rifampicin/vancomycin treatment

Broekhuizen, Corine A.N.; Boer, Leonie de; Schipper, Kim; Jones, Christopher D.; Quadir, Shan; Vandenbroucke-Grauls, Christina M. J. E.; Zaat, Sebastian A. J.

doi:10.1002/jbm.a.31528

Cited by 35 publications

(23 citation statements)

References 50 publications

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“…It was believed that the phenotypic switching of S. aureus may make the bacteria more resistant to antibiotics [[17],[42]]. Similarly, S. epidermidis was found to persist in macrophages and also in peri-implant tissues in mice despite antibiotic treatments [[43],[44]]. The survival of S. aureus within cells like macrophages and osteoblasts and the possible phenotypic switching of S. aureus may explain why antibiotics have so often failed to cure Staphylococcal infections [[2],[17],[36]].…”

Section: Discussionmentioning

confidence: 99%

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Hamza

2014

BMC Microbiol

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BackgroundStaphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization.ResultsWe found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureus infection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells.ConclusionsS. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells.

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Section: Discussionmentioning

confidence: 99%

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Hamza

2014

BMC Microbiol

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“…Explaining the clinical picture of indolent infection and treatment resistance, S. epidermidis strains are able to survive intracellularly in a quiet state in phagocytic cells and in peri-implant macrophage-like cells [26]. They can invade even into osteoblasts [27,28]. All these features explain the limited inflammatory host response to S. epidermidis infections and reflect in the low uptake of the 18 F-FDG tracer.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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Background18F-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.MethodsTwenty-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.ResultsThe 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.ConclusionThe peri-implant inoculation of S. epidermidis, reflecting low virulence of the pathogen and limited leukocyte infiltration, was characterized by low 18 F-FDG uptake.

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“…This hypothesis was later tested with interleukin‐1 receptor‐deficient mutant mice [31]; these mice were significantly less likely to develop infection. This is an important finding, because the persistence of intracellular pathogens around an implanted biomaterial is a major concern, as these bacteria are not as susceptible to antibiotic treatment as those associated directly with the implant [32].…”

Section: Host Response To Biomaterials and Infectionmentioning

confidence: 99%

Influence of material on the development of device-associated infections

Rochford

Richards

Moriarty

2012

Clinical Microbiology and Infection

106

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The use of implanted devices in modern orthopaedic surgery has greatly improved the quality of life for an increasing number of patients, by facilitating the rapid and effective healing of bone after traumatic fractures, and restoring mobility after joint replacement. However, the presence of an implanted device results in an increased susceptibility to infection for the patient, owing to the creation of an immunologically compromised zone adjacent to the implant. Within this zone, the ability of the host to clear contaminating bacteria may be compromised, and this can lead to biofilm formation on the surface of the biomaterial. Currently, there are only limited data on the mechanisms behind this increased risk of infection and the role of material choice. The impacts of implant material on bacterial adhesion, immune response and infection susceptibility have been investigated individually in numerous preclinical in vitro and in vivo studies. These data provide an indication that material choice does have an impact on infection susceptibility; however, the clinical implications remain to be clearly determined.

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Staphylococcus epidermidis is cleared from biomaterial implants but persists in peri‐implant tissue in mice despite rifampicin/vancomycin treatment

Cited by 35 publications

References 50 publications

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

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

Influence of material on the development of device-associated infections

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