Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model

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

doi:10.1007/s00264-014-2582-9

Cited by 27 publications

(20 citation statements)

References 32 publications

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“…Representative animal models of osteomyelitis are valuable tools since they allow diagnostic and therapeutic research to keep moving forward [11]. Experimental handling of such animal models of infection diseases usually involves microbiological evaluation of the infected organ and searching for macro or micro changes in it such as bacterial colonization as well as morphological and histopathological changes [12][13][14][15]. The evaluation of these parameters is related, in a non negotiable way, to animal euthanasia which avoids the follow up of the same animal during the development of the disease or even worse, the follow up of a treatment using the same animal.…”

Section: Discussionmentioning

confidence: 99%

99mTc-Ciprofloxacin Imaging: Still an Unsettled Issue?

Salgueiro¹

2016

Int. J. Nucl. Medi. Res.

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The objective of this work consisted in the assessment of 99mTc-ciprofloxacin imaging performance as a diagnostic tool in an experimental rat model of osteomyelitis. Bone (tibia) infection was induced in adult rats by inoculation of a suspension containing S. aureus suspended in fibrin glue. In vivo studies by means of small animal imaging were conducted using a gamma camera. The study shows the correlation between 99mTc-ciprofloxacin positive images with bacterial bone count but also with histopathological findings in an osteomyelitis animal model, highlighting its potential as a tool in preclinical research and the accomplishment of 3Rs concept regarding welfare of laboratory animals. 99mTc-MDP scintigraphy, failed to show these correlations and therefore it may be proposed as a complementary method to diagnose and follow up the bone physiopathology in this animal model. Future perspectives of small animal imaging in order to potentiate osteomyelitis basic research will derive from numerous research works, and 99mTc-ciprofloxacin may still be a candidate for infectious diagnose and follow-up as demonstrated in this study.

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Section: Discussionmentioning

confidence: 99%

99mTc-Ciprofloxacin Imaging: Still an Unsettled Issue?

Salgueiro¹

2016

Int. J. Nucl. Medi. Res.

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“…Regardless of the drug, antibiotic-coated implants generally showed a 0.3–4.5 log-reduction of colonized bacteria (MSSA or MRSA) in bone and 0.35–4.5 log-reduction on implants in comparison to a non-coated control. 204,207,211,213,217–219 Diefenbeck et al demonstrated that plasma chemically oxidized titanium rods coated with gentamicin and gentamicin+tannic acid showed 100% and 90% protection in a rat tibia infection model. 214 Additionally, Metsemakers et al demonstrated highly favorable results in a rabbit infection model, where doxycycline-coated intramedullary nails had 100% protection against MSSA (JAR060131; doxycycline-susceptible clinical isolate) and 43% protection against MRSA (LUH15101; doxycycline-resistant clinical isolate).…”

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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“…Rabbits have traditionally been preferred models for joint arthroplasty, however rat models are increasingly being developed . Due to their smaller size, rodents are rarely suitable for looking at implant biomechanics, but can be very effective for examining the osseointegration of implants with novel biomaterial surfaces, in conjunction with new biological agents, and/or in the presence of infection …”

Section: Orthopedic and Bone Tissue Engineering Modelsmentioning

confidence: 99%

Preclinical models for orthopedic research and bone tissue engineering

Mills

Bobyn

Little

2017

Journal Orthopaedic Research

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In this review, we broadly define and discuss the preclinical rodent models that are used for orthopedics and bone tissue engineering. These range from implantation models typically used for biocompatibility testing and high-throughput drug screening, through to fracture and critical defect models used to model bone healing and severe orthopedic injuries. As well as highlighting the key methods papers describing these techniques, we provide additional commentary based on our substantive practical experience with animal surgery and in vivo experimental design. This review also briefly touches upon the descriptive and functional outcome measures and power calculations that are necessary for an informative study. Obtaining informative and relevant research outcomes can be very dependent on the model used, and we hope this evaluation of common models will serve as a primer for new researchers looking to undertake preclinical bone studies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:832-840, 2018.

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Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model

Abstract: Gentamicin palmitate appears to be a viable coating for the prevention of implant-associated infections. These findings will have to be confirmed in larger animal models as well as in clinical trials.

Cited by 27 publications

References 32 publications

99mTc-Ciprofloxacin Imaging: Still an Unsettled Issue?

99mTc-Ciprofloxacin Imaging: Still an Unsettled Issue?

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

Preclinical models for orthopedic research and bone tissue engineering

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