Impact of prophylactic CpG Oligodeoxynucleotide application on implant-associated Staphylococcus aureus bone infection

Sethi, Shneh; Thormann, Ulrich; Sommer, Ursula; Stötzel, Sabine; Mohamed, Walid; Schnettler, Reinhard; Domann, Eugen; Chakraborty, Trinad; Alt, Volker

doi:10.1016/j.bone.2015.04.030

Cited by 14 publications

(11 citation statements)

References 54 publications

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“…Periosteal reaction, cortical thickening, myeloid hyperplasia, polymorphonuclear cells in the granulation tissue were observed. 46,47 These findings suggest that both pro-and anti-inflammatory reactions are present during the progression of post-traumatic osteomyelitis.…”

Section: Pathophysiology Of Periprosthetic Joint Infectionmentioning

confidence: 86%

“…Either S. aureus or S. epidermidis contamination has been used for creation of infected non-union animal models of osteomyelitis. 46,47 In a rat model of S. aureus induced bone infection after tibial osteotomy, cytokine and chemokine analyses of bone tissue homogenates showed that the infected bone had increased concentrations of proinflammatory mediators including interleukin-1b (IL-1b) and macrophage inflammatory protein-2 (MIP-2) etc. as early as day 1 after infection.…”

Section: Pathophysiology Of Periprosthetic Joint Infectionmentioning

confidence: 99%

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Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies

Birt

Anderson

Toby

et al. 2017

Journal of Orthopaedics

176

127

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This review article summarizes the recent advances in pathogenic mechanisms and novel therapeutic strategies for osteomyelitis, covering both periprosthetic joint infections and fracture-associated bone infections. A better understanding of the pathophysiology including the mechanisms for biofilm formation has led to new therapeutic strategies for this devastating disease. Research on novel local delivery materials with appropriate mechanical properties, lower exothermicity, controlled release of antibiotics, and absorbable scaffolding for bone regeneration is progressing rapidly. Emerging strategies for prevention, early diagnosis of low-grade infections, and innovative treatments of osteomyelitis such as biofilm disruptors and immunotherapy are highlighted in this review.

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Section: Pathophysiology Of Periprosthetic Joint Infectionmentioning

confidence: 86%

Section: Pathophysiology Of Periprosthetic Joint Infectionmentioning

confidence: 99%

Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies

Birt

Anderson

Toby

et al. 2017

Journal of Orthopaedics

176

127

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“…Due to the nonspecific mode-of-action of immunological adjuvants, they can establish broad range protection to different microorganisms by employing cell recruitment, elevated phagocytosis, and enhanced ROS production. [316][317][318][319] Of the many available adjuvants, monophosphoryl lipid A (MPLA), [316,320] CpG oligodeoxynucleotides (CpG ODN), [320][321][322] and β-glucans [323] have proven to be particularly effective in protecting against Staphylococcal infections. [316,320,321,323] Table 1 summarizes the advantages and limitations associated with the use of adjuvants in anti-infective biomaterials.…”

Section: Adjuvants For Innate Immunity Trainingmentioning

confidence: 99%

“…As a potential caveat, the innate immune training concept takes its advantage form the metabolic programming of host cells. As this requires several days to come into effect, [322,332] the elevated immune protection could be hampered in the first postoperative days, that is, when a surgeryrelated infection is most likely to occur. Of note, the priming of innate immunity may not be limited to PRR ligands, as it was recently shown that gold nanoparticles reprogram human monocyte to respond differently to a secondary microbial challenge.…”

Section: Adjuvants For Innate Immunity Trainingmentioning

confidence: 99%

Combating Implant Infections: Shifting Focus from Bacteria to Host

et al. 2020

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commensal skin bacteria, Staphylococci, and in particular Staphylococcus aureus, have a strong tendency to colonize foreign bodies and cause IAI. [3,4] Important for the underlying pathophysiology, Staphylococci are highly competent at producing biofilms on implant surfaces, which encapsulate the bacterial niche from the outside environment, [5,6] thereby protecting the bacteria from host defense systems and antibiotics. [7] Antibiotics are administered as a routine procedure. [8] However, as a consequence of widespread antibiotics usage, bacteria are exposed to subinhibitory concentrations of antibiotics at a larger scale, driving their development toward antibiotic resistance, [9] as illustrated by the emergence of methicillin-resistant S. aureus (MRSA). [10,11] As an improvement over current clinically applied local antibiotics delivery systems, [12] the recent developments in implant surface engineering approaches allow better antimicrobial functionalities to be incorporated to allow for more tunable and controlled drug release. [13-15] The "race to the surface" model is popular among biomaterials researchers to predict the biomaterials fate, resulting from the competition between eukaryotic cells and bacteria at the material surface. [16] Using this template, implant antibacterial properties are being stemmed from direct contact killing mechanisms due to implant surface modifications [17,18] or firm immobilization of drugs, [19,20] as they both "shield" the implant from bacterial adhesion. The current anti-infective biomaterials strategies being explored can be categorized as: 1) implant functionalization with antibiotics or antibacterial drugs such as host defense peptides (HDPs), inorganic materials (e.g., chitosan and derivatives), and inorganics (e.g., silver, copper, and zinc metal nanoparticles (NPs)), 2) anti-biofilm surface modification (e.g., coating with antifouling polymers or quorum sensor inhibitors), or 3) physical surface changes for direct contact-killing properties (e.g., nanotubes, nanopillars, and metal implantation). [15,21] Emerging as a serious alternative or adjuvant therapy to antibiotics, bacteriophage (phage) therapy uses viruses responsible for the lysis of specific bacterial strains. [22,23] As a natural predator of bacteria, phages employ different killing mechanisms, making multidrug resistant bacteria susceptible for phages. [24] Moreover, phages are highly specific for pathogenic cells, which can eliminate disastrous off-target effects in the host. [25] As a limitation, the use of phage cocktails is needed for therapeutic efficacy, [26] while there is currently is no conclusive data on possible long-term side effects of phage therapy in The widespread use of biomaterials to support or replace body parts is increasingly threatened by the risk of implant-associated infections. In the quest for finding novel anti-infective biomaterials, there generally has been a one-sided focus on biomaterials with direct antibacterial properties, which leads to excessive use of antibacterial ag...

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“…Ter Boo et al, 2016;Boyce et al, 2012;Costa et al, 2016;Darouiche et al, 1998;Fei et al, 2010;Hill et al, 2002;Hill and Watkins, 2001;Jacob et al, 1993;Jacob et al, 1997;Lesic et al, 2004;Li et al, 2009;Lindsey et al, 2010a;Lovati et al, 2016a;Metsemakers et al, 2016;Penn-Barwell et al, 2012a;Penn-Barwell et al, 2012b;Penn-Barwell et al, 2015;Schaer et al, 2012;Sethi et al, 2015;Stewart et al, 2010;Stewart et al, 2012;Tennent et al, 2016;Windolf et al, 2014;Worlock et al, 1994;Xiao et al, 2015;Xie et al, 2009;Zheng et al, 2010;Zhou et al, 2017 Bone healing 9…”

Section: Model Description 11mentioning

confidence: 99%

Preclinical in vivo models of fracture-related infection: a systematic review and critical appraisal

Vanvelk¹,

Morgenstern²,

Moriarty³

et al. 2018

eCM

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A fracture-related infection (FRI) is an important complication that can lead to an increase in morbidity, mortality and economic costs. Preclinical in vivo models are critical in the evaluation of novel prevention and treatment strategies, yet it is important that these studies recapitulate the features of an FRI that make it such a clinical challenge. The aim of this systematic review was to survey the available preclinical models of FRIs and assess which of the key FRI-specific parameters are incorporated in these models. A comprehensive search was performed on July 1 st 2017 in PubMed, Embase and Web of Science. Overall, 75 preclinical studies were identified, 97.3 % (n = 73) of which use Staphylococcus aureus as the causative microorganism. The most common mode for creation of bone instability is an osteotomy (n = 30; 40 %), followed by the creation of a defect (n = 26; 34.7 %). An actual fracture is created in only 19 studies (25.3 %). 12 (16 %) of the models include a time gap between bacterial inoculation and fixation to mimic the time-totreatment in clinical open fracture scenarios. This systematic review reveals that animal models used in translational research on prevention and treatment of FRIs rarely incorporate all key clinical features in one model and that there is an overrepresentation of S. aureus in comparison to actual clinical epidemiology. To improve the relevance of these studies, existing preclinical models should be adapted or new models developed that better recapitulate the clinical condition of an FRI.

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Impact of prophylactic CpG Oligodeoxynucleotide application on implant-associated Staphylococcus aureus bone infection

Cited by 14 publications

References 54 publications

Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies

Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies

Combating Implant Infections: Shifting Focus from Bacteria to Host

Preclinical in vivo models of fracture-related infection: a systematic review and critical appraisal

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