Systemic antibiotic therapy does not significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus

Fölsch, Christian; Federmann, Maike; Lakemeier, Stefan; Kuehn, Klaus Dieter; Kittinger, Clemens; Kerwat, Martina; Fuchs-Winkelmann, Susanne; Paletta, Jürgen R. J.; Roessler, Philip P.

doi:10.1007/s00402-016-2419-7

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…213–215 Gentamicin is the most studied antibiotic in coatings because of its application in the clinic for treating methicillin-sensitive S. aureus (MSSA) bone-related infections. 203,204,206–208,210,211,213,214,216–218 Vancomycin, commonly used to treat MRSA infections, has also been incorporated into implant coatings. 212,215,219 Additional antibiotics such as fosfomycin, 204 doxycycline, 209 minocycline, 20 rifampin, 20 colistin, daptomycin, and cefoxitin have also been incorporated into implant coatings.…”

Section: Novel Antibiotic Therapies To Combat Osteomyelitismentioning

confidence: 99%

Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

et al. 2019

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Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast, S. aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

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Section: Novel Antibiotic Therapies To Combat Osteomyelitismentioning

confidence: 99%

Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

et al. 2019

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“…Haptoglobin has been used to track infection and success of treatment in 5‐month‐old male Sprague Dawley rats receiving femoral injections of methicillin‐susceptible S . aureus (MSSA) into the intermedullary cavity 48 . Rats receiving a gentamicin‐coated K‐wire implant with intraperitoneal (IP) gentamicin sulfate injection (combination group) showed decreased levels of haptoglobin on Days 7, 28, and 42 compared to uncoated implant alone (control) 48,49 .…”

Section: Models Of Injury + Infectionmentioning

confidence: 99%

Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models

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et al. 2022

Journal Orthopaedic Research

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Disease or trauma of orthopedic tissues, including osteomyelitis, osteoporosis, arthritis, and fracture, results in a complex immune response, leading to a change in the concentration and milieu of immunological cells and proteins in the blood. While C-reactive protein levels and white blood cell counts are used to track inflammation and infection clinically, controlled longitudinal studies of disease/injury progression are limited.Thus, the use of clinically-relevant animal models can enable a more in-depth understanding of disease/injury progression and treatment efficacy. Though longitudinal tracking of immunological markers has been performed in rat models of various inflammatory and infectious diseases, currently there is no consensus on which markers are sensitive and reliable for tracking levels of inflammation and/or infection. Here, we discuss the blood markers that are most consistent with other outcome measures of the immune response in the rat, by reviewing their utility for longitudinal tracking of infection and/or inflammation in the following types of models: localized inflammation/arthritis, injury, infection, and injury + infection. While cytokines and acute phase proteins such as haptoglobin, fibrinogen, and α 2 -macroglobulin demonstrate utility for tracking immunological response in many inflammation and infection models, there is likely not a singular superior marker for all rat models. Instead, longitudinal characterization of these models may benefit from evaluation of a collection of cytokines and/or acute phase proteins.Identification of immunological plasma markers indicative of the progression of a pathology will allow for the refinement of animal models for understanding, diagnosing, and treating inflammatory and infectious diseases of orthopedic tissues.

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“…The increasing number of joint replacement revision surgery for infectious disease is challenging (Frommelt 2018 ; Li et al 2013 ). Local application of antibiotics within impacted bone graft appears useful in case of prevention or treatment of infection (Coraca-Huber et al 2016 ; Fölsch et al 2015 , 2016a ; Lewis et al 2012 ). Suitable carrier substances provide high local antibiotic concentrations (Frommelt 2018 ) and should improve mechanic properties of the impacted bone graft.…”

Section: Introductionmentioning

confidence: 99%

Effect of synthetic bone replacement material of different size on shear stress resistance within impacted native and thermodisinfected cancellous bone: an in vitro femoral impaction bone grafting model

et al. 2021

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Antibiotic carrier particles of variable size might influence mechanic properties within impacted thermodisinfected and native cancellous bone different. Herafill®G containing calciumsulfate and calciumcarbonate provides high local concentrations of gentamicin being important for revision surgery in infected joint replacements. Native and thermodisinfected cancellous bone derived from 6 to 7 months old piglets was used for in vitro impaction bone grafting and supplemented each with Herafill®G granules of two different sizes. Micromovement of implants related to shear force was measured in 29 specimens distributed in 6 groups. Thermodisinfected cancellous bone revealed a significant higher shear force resistance than native bone with a mean difference of 423.8 mdeg/Nm (p < 0.001) ranging within 95% confidence interval from 181.5 to 666.0 mdeg/Nm. Adding small granules to thermodisinfected bone did not reduce shear force resistance significantly since adding large granules to native bone improved it by 344.0 mdeg/Nm (p < 0.003). Shear force resistance was found higher at the distal region of the implant compared to a proximal point of measurement throughout all specimens. Less impaction impulses were necessary for thermodisinfected bone. Thermodisinfected cancellous bone might achieve a higher degree of impaction compared with native bone resulting in increased resistance against shear force since impaction was found increased distally. Supplementation of thermodisinfected bone with small granules of Herafill®G might be considered for application of local antibiotics. Large granules appeared more beneficial for supplementation of native bone. Heterogeneity of bone graft and technical aspects of the impaction procedure have to be considered regarding the reproducibility of femoral impaction bone grafting.

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Systemic antibiotic therapy does not significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus

Abstract: Systemic perioperative and implant-associated application of antibiotics were both comparably effective to treat implant-associated infections whereas the combined antibiotic therapy further reduced systemic signs of infection time dependent.

Cited by 8 publications

References 31 publications

Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models

Effect of synthetic bone replacement material of different size on shear stress resistance within impacted native and thermodisinfected cancellous bone: an in vitro femoral impaction bone grafting model

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