A Model for Chronic Osteomyelitis Using Staphylococcus aureus in Goats

Salgado, Christopher J.; Jamali, Amir A.; Mardini, Samir; Buchanan, Kelvin C.; Veit, Bruce C.

doi:10.1097/01.blo.0000159154.17131.bf

Cited by 22 publications

(11 citation statements)

References 7 publications

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“…First, the field has been overly concerned with intramedullary implant models, since this represents the more serious clinical condition. [8][9][10][11][12][13] Unfortunately, we found that this IMPLANT-ASSOCIATED OSTEOMYELITIS model gave rise to highly variable (temporal and spatial) lesions, making a reproducible, quantitative model very challenging, although others have recently succeeded. 24 In contrast, we have found that implantation of an infected transcortical pin always produces lesions adjacent to the pin, and never results in distal OM, hematogenous infection, or death (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…As such, biofilm biology, which plays a critical role in resistance of chronic OM to antibiotic therapy by serving as a dominant protective barrier from the action of antibiotics, can only be studied with in vivo models. 4 To date, much of our knowledge of the pathogenesis of OM comes from animal models, 5 which have existed in chicken, 6 rat, 7,8 guinea pig, 9 rabbit, 10 dog, 11 sheep, 12 goat, 13 and most recently mouse. 14 While these models have been used to confirm the importance of bacterial adhesions identified from in vitro assays, [15][16][17] none of them contain quantitative endpoints that can determine bacterial load or growth in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

Gromov

Søballe

et al. 2007

Journal Orthopaedic Research

140

165

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Although osteomyelitis (OM) remains a serious problem in orthopedics, progress has been limited by the absence of an in vivo model that can quantify the bacterial load, metabolic activity of the bacteria over time, immunity, and osteolysis. To overcome these obstacles, we developed a murine model of implant-associated OM in which a stainless steel pin is coated with Staphylococcus aureus and implanted transcortically through the tibial metaphysis. X-ray and micro-CT demonstrated concomitant osteolysis and reactive bone formation, which was evident by day 7. Histology confirmed all the hallmarks of implant-associated OM, namely: osteolysis, sequestrum formation, and involucrum of Gram-positive bacteria inside a biofilm within necrotic bone. Serology revealed that mice mount a protective humoral response that commences with an IgM response after 1 week, and converts to a specific IgG2b response against specific S. aureus proteins by day 11 postinfection. Real-time quantitative PCR (RTQ-PCR) for the S. aureus specific nuc gene determined that the peak bacterial load occurs 11 days postinfection. This coincidence of decreasing bacterial load with the generation of specific antibodies is suggestive of protective humoral immunity. Longitudinal in vivo bioluminescent imaging (BLI) of luxA-E transformed S. aureus (Xen29) combined with nuc RTQ-PCR demonstrated the exponential growth phase of the bacteria immediately following infection that peaks on day 4, and is followed by the biofilm growth phase at a significantly lower metabolic rate (p < 0.05). Collectively, these studies demonstrate the first quantitative model of implant-associated OM that defines the kinetics of microbial growth, osteolysis, and humoral immunity following infection. ß

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

Gromov

Søballe

et al. 2007

Journal Orthopaedic Research

140

165

View full text Add to dashboard Cite

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“…Where the caprine studies benefit most compared to small animal models as highlighted by Salgado et al 91 and Curtis et al 82 is their comparative size in terms of osteology and ability to use standard osteosynthesis techniques and instruments. This comparison is not limited to internal fixation and a number of studies have used goats as experimental models for the study of external fixation 92–96…”

Section: Non-projectile Large Animal Extremity Injury Modelsmentioning

confidence: 99%

Modelling for conflict: the legacy of ballistic research and current extremity in vivo modelling

Eardley¹,

Watts

2013

J R Army Med Corps

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Extremity ballistic injury is unique and the literature intended to guide its management is commonly misinterpreted. In order to care for those injured in conflict and conduct appropriate research, clinicians must be able to identify key in vivo studies, understand their weaknesses and desist the propagation of miscited and misunderstood ballistic dogma. This review provides the only inclusive critical overview of key studies of relevance to military extremity injury. In addition, the non-ballistic studies of limb injury, stabilisation and contamination that will form the basis from which future small animal extremity studies are constructed are presented. With an awareness of the legacy of military wound models and an insight into available generic models of extremity injury and contamination, research teams are well placed to optimise future military extremity injury management.

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“…11 More recently developed sheep, goat, and dog largeanimal models permit manipulation of surgical parameters as well as evaluation of antimicrobial therapy. 12,13 Animal models have contributed to understanding of revascularization and bone remodeling that occur after infection and debridement and have demonstrated effectiveness of agents such as clindamycin and rifampin-containing combinations in S. aureus infections. 11,12 However, some drugs are toxic in animal models, and for others there is poor correlation between animal data and clinical experience.…”

Section: Lessons From Animal Models Of Antimicrobial Therapy In Osteomentioning

confidence: 99%

Systemic Antimicrobial Therapy in Osteomyelitis

Fraimow

2009

Seminars in Plastic Surgery

124

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Appropriately designed antibiotic regimens are critical to the management of all stages of osteomyelitis, although goals of therapy may vary in different stages of infection. The most important consideration for antibiotic selection is spectrum of action. Route of administration by intravenous or oral route is less important than drug levels that are achievable at the site of infection. Outpatient parenteral therapy and use of oral agents has simplified delivery of long-term treatment regimens. There are few high-quality studies that compare specific treatment regimens or durations of therapy, and recommendations for drugs and duration of antibiotic therapy are based on expert opinion, case series, and extrapolations from animal models. Intravenous beta-lactams are the treatment of choice for methicillin-susceptible Staphylococcus aureus, but there are also oral options available. Vancomycin has been the treatment of choice for methicillin-resistant Staphylococcus aureus osteomyelitis, but there are several newer parenteral and oral agents for treatment of methicillin-resistant Staphylococcus aureus including linezolid and daptomycin. Rifampin combined with other staphylococcal agents may increase cure rates, especially for device-associated infections. Oral fluoroquinolones and parenteral beta-lactam agents can be used for treatment of gram-negative osteomyelitis, but increasing resistance has complicated management of these infections.

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A Model for Chronic Osteomyelitis Using Staphylococcus aureus in Goats

Cited by 22 publications

References 7 publications

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

Modelling for conflict: the legacy of ballistic research and current extremity in vivo modelling

Systemic Antimicrobial Therapy in Osteomyelitis

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