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Objectives: Open fractures are at significant risk of developing a fracture-related infection, despite the routine administration of perioperative antibiotic prophylaxis. Early application of antibiotic prophylaxis is known to reduce infection rates; however, most international guidelines focus on postoperative duration rather than prehospital administration. We compared conventional perioperative prophylaxis against early prehospital prophylaxis either as a systemic single shot of cefuroxime or a locally applied gentamicin-loaded hydrogel in a laboratory animal model., Methods: Thirty New Zealand white rabbits underwent a first surgical procedure to create an open wound, bone damage and contamination with Staphylococcus aureus. After a 4-hour observation period mimicking the time-to-treatment, the animals underwent a second procedure to irrigate the wound and apply a fracture fixation device. The 5 groups (n = 6 per group) received (1) no treatment; (2) conventional 24-hour cefuroxime; (3) an early single shot of cefuroxime 15 minutes after trauma; (4) a combined early and standard systemic prophylaxis; and (5) early application of a gentamicin-loaded hydrogel that was removed during irrigation., Results: Untreated animals displayed high numbers of bacteria in irrigation fluid and were all highly culture positive at euthanasia. Three of 6 animals were culture positive at euthanasia after conventional prophylaxis. Early systemic prophylaxis reduced bacterial burden in irrigation fluid by up to 100-fold, but 5/6 animals were culture positive at euthanasia. The combined prophylaxis displayed greater efficacy with only 1/6 rabbits culture positive at euthanasia. Local application of the gentamicin-loaded hydrogel reduced bacteria recovered by irrigation to just above our detection limit, and at euthanasia, all animals were culture negative at euthanasia., Conclusions: Early systemic antibiotic administration can significantly reduce bacterial burden in the operative field and reduce culture positivity at euthanasia when continued for 24 hours after injury. The early application of a gentamicin-loaded hydrogel that was removed during irrigation displayed superior efficacy to early systemic therapy alone and postoperative conventional gold standard 24-hour systemic therapy alone. These experimental results highlight the importance of early antibiotic administration in fracture care.

Fracture-related infection (FRI) remains a challenging complication that imposes a heavy burden on orthopaedic trauma patients. The surgical management eradicates the local infectious focus and if necessary facilitates bone healing. Treatment success is associated with debridement of all dead and poorly vascularized tissue. However, debridement is often associated with the formation of a dead space, which provides an ideal environment for bacteria and is a potential site for recurrent infection. Dead space management is therefore of critical importance. For this reason, the use of locally delivered antimicrobials has gained attention not only for local antimicrobial activity but also for dead space management. Local antimicrobial therapy has been widely studied in periprosthetic joint infection, without addressing the specific problems of FRI. Furthermore, the literature presents a wide array of methods and guidelines with respect to the use of local antimicrobials. The present review describes the scientific evidence related to dead space management with a focus on the currently available local antimicrobial strategies in the management of FRI. LEVEL OF EVIDENCE:: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

Objectives: The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial because of heterogeneous or unclear guidelines and highly variable prophylactic regimens in clinical practice. We aimed at testing different PAP durations under controlled conditions in a contaminated rabbit fracture model., Methods: A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole locking compression plate and inoculated with Staphylococcus aureus. Cefuroxime was administered in a weight-adjusted dosage equivalent to human medicine (18.75 mg/kg). PAP was administered as a single shot only; for 24 hours; or for 72 hours in separate groups of rabbits (n = 6 per group). Infection was assessed after 2 weeks by quantitative bacteriological evaluation of the tissues and hardware., Results: Postoperative duration of PAP had a significant impact on the success of antibiotic prophylaxis in this model. Whereas the single-shot regimen completely failed to prevent infection, the 24-hour regimen showed a reduced infection rate (1 of 6 rabbits infected), but only the 72-hour course was able to prevent fracture-related infection in all animals in our model., Conclusions: When contamination with high bacterial loads is likely (eg, in an open fracture situation), a 72-hour course of intravenous cefuroxime seems to be superior in preventing fracture-related infection in our rabbit model compared with a single-shot or 24-hour antibiotic regimen.

Tremendous advances in quality, reliability, performance, and versatility of surgical instrumentation and devices have been achieved over the past 50 years using biomaterials. The global orthopaedic implant industry is expected to grow to $41.8 billion by 2016, driven primarily by advancements in implant designs, including materials that provide improved biocompatibility, durability, and expanded clinical applications. Biomaterials have evolved through 3 clinical "generations": (1) "bio-inert materials," (2) materials with intrinsic bioactivity and degradability, and (3) biomaterials that stimulate specific biological host responses. In all cases, surface modifications, including coatings, represent a key strategy for improvements in tissue-contacting properties. Surfaces continue to be a focus for many device improvements and for tissue interfacing, especially for many orthopaedic structural implants comprising metal and metal alloys. Progress in implant materials processing, coating technologies, and coating combinations with therapeutic agents provide new properties and functionalities to improve device-tissue integration and reduce foreign body reactions and infections. Performance criteria for these surface modifications success in clinical practice are daunting, and translation of several technologies from in vitro proof-of-concept to in vivo applications has proven challenging.

Preclinical modeling of human disease with animals has not been standardized for many common pathologic processes. Assorted animal models are being used to investigate the pathogenesis, prevention, and treatment of disease processes. Certainly it is difficult to interpret the current literature because there are diverse and often irrelevant models being implemented. Some models are used for reasons of size or ease rather than the true modeling of a physiological process. Application to granting agencies and design of animal studies is difficult without standardization of the ideal preclinical model for disease states. The current article addresses the preclinical animal modeling of osteoporosis, infection, bone defects, and cartilage injury. This article is a discussion of the current literature, commonly used models, and suggests preferred preclinical models for future research design.