Animal Models of Orthopedic Implant-Related Infection

Calabrò, Lorenzo; Lutton, Cameron; Din, Ahmed Fouad Seif El; Richards, R. Geoff; Moriarty, T. Fintan

doi:10.1007/978-1-4614-1031-7_12

Cited by 13 publications

(14 citation statements)

References 144 publications

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“…A wide range of in vivo ODRI models are also available (reviewed in refs. ), ranging from the comparatively simple models amenable to most institutions and facilities, to the more complex models requiring more advanced expertise and facilities and finally the most complex models where the clinical condition is recapitulated to the closest extent possible . Figure outlines the types of animal models available, arranged according to complexity and appropriateness to different stages of product development.…”

Section: Key Aspects In Model Selection Animal Welfare Reporting Anmentioning

confidence: 99%

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

Moriarty

Harris

Mooney

et al. 2019

Journal Orthopaedic Research

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Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drugdevice combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience-driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation.

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Section: Key Aspects In Model Selection Animal Welfare Reporting Anmentioning

confidence: 99%

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

Moriarty

Harris

Mooney

et al. 2019

Journal Orthopaedic Research

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“…154 However, to our knowledge, testing of QSIs in an appropriate animal model for orthopaedic device-associated biofilm infections has not yet been done, although several foreign body models mimicking biofilm infections on prosthetic devices are available. 155,156 …”

Section: New Approaches For Prevention and Treatmentmentioning

confidence: 99%

Orthopaedic device-related infection: current and future interventions for improved prevention and treatment

et al. 2016

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Orthopaedic and trauma device-related infection (ODRI) remains one of the major complications in modern trauma and orthopaedic surgery.Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, leading to infections that negatively impact clinical outcome and significantly increase healthcare expenditure.The following review summarises the microbiological profile of modern ODRI, the impact antibiotic resistance has on treatment outcomes, and some of the principles and weaknesses of the current systemic and local antibiotic delivery strategies.The emerging novel strategies aimed at preventing or treating ODRI will be reviewed. Particular attention will be paid to the potential for clinical impact in the coming decades, when such interventions are likely to be critically important.The review focuses on this problem from an interdisciplinary perspective, including basic science innovations and best practice in infectious disease. IntroductionOrthopaedic and trauma device-related infection (ODRI) remains a major complication in modern trauma and orthopaedic surgery. 1 Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, and can lead to infections that negatively impact clinical outcome and significantly increase healthcare expenditure. 2 Pre-operative and correctly-timed prophylactic antibiotic intervention is mandatory for a majority of orthopaedic procedures. However, despite this, the incidence of infection following elective orthopaedic surgery is in the range of 0.7% to 4.2%, 3-7 while the incidence can be much higher in trauma cases where infection rates range from approximately 1% after operative fixation of closed low-energy fractures, to more than 30% in complex open tibia fractures. 8,9 Treatment success rates vary, with between 57% and 88% often reported. [10][11][12] Current curative approaches (radical debridement, revision surgery and prolonged antibiotic therapy) often result in significant socioeconomic costs, not to mention the risk of life-long functional impairment for the patient. Against this background, and with the increasing issue of antibiotic-resistant bacteria, the problem of ODRI is set to continue to pose a challenge for practising clinicians in the coming decades. The clinical and microbiological challenges of modern device-related infectionsThe most prevalent species in ODRIs are Staphylococci. [13][14][15][16][17] Staphylococcus (S.) aureus accounts for between 20% and 30% of cases of infection after fracture fixation and prosthetic joint infections (PJI), with coagulase-negative staphylococci (CoNS) accounting for 20%-40% of cases, [13][14][15][16] including small colony variants. 18 Other Gram-positive cocci including Streptococci (1%-10%) and Enterococci (3%-7%) are less frequently encountered. Infections caused by Gram-negative bacilli, including Pseudomonas aeruginosa and Enterobacteriaceae account for approximately 6%-17%, [13][14][15][16...

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“…Infection is one of the most common and costly complications in orthopedic surgery, particularly when it occurs in the bone and surrounding tissues (Calabro et al 2013). Consequently, it imposes a significant health care and economic burden on society (Darouiche 2004;Edwards et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Increased Effects of Extracorporeal Shock Waves Combined with Gentamicin against Staphylococcus aureus Biofilms In Vitro and In Vivo

Zhao

Han

et al. 2016

Ultrasound in Medicine & Biology

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Animal Models of Orthopedic Implant-Related Infection

Cited by 13 publications

References 144 publications

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

Orthopaedic device-related infection: current and future interventions for improved prevention and treatment

Increased Effects of Extracorporeal Shock Waves Combined with Gentamicin against Staphylococcus aureus Biofilms In Vitro and In Vivo

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