Initial Antibiotics

Three moderate quality studies (Hendrickson 2020, Weber 2014, Westgeest 2016) have examined the effectiveness of early antibiotics in the setting of open fracture for prevention of deep infection. Two moderate studies (Lack 2015 and Roddy 2020) compared time from arrival to the emergency department, while one moderate study (Zuelzer 2020) compared time from injury to antibiotic delivery. While the timing was somewhat different between these studies, all three demonstrated that the earliest feasible timing of antibiotic administration reduced the risk of deep infection. Investigation of the effectiveness of early antibiotics for the prevention of other adverse events in the setting of open fracture, such as nonunion or wound complications, has been limited to date, without any significant differences seen in one moderate quality study (Westgeest 2016).

Benefits & Harms
The potential benefit of early antibiotic treatment is prevention of deep infection. The potential harms of antibiotic administration include allergy (including anaphylaxis), microbiome disturbances, Clostridioides difficile infection and selection of antibiotic resistance.

Outcome Importance
Development of deep infection after major extremity trauma can lead to severe morbidity, prolonged hospitalization, and significantly increased utilization of healthcare resources. 

Cost Effectiveness/Resource Utilization
The cost of prophylactic antibiotic dosing is significantly less than what is required for treatment of deep infection.

Feasibility
While seemingly feasible, the treatment of major extremity trauma is frequently not an isolated entity and may not always be the most pressing issue in the setting of severe trauma. It is important that the healthcare professionals responsible for the musculoskeletal care of patients with major lower extremity trauma be aware of and advocate for the earliest feasible timing for administration of antibiotics in this setting.

Future Research
Future research is needed to further refine the threshold on timing of early antibiotic treatment for the prevention of deep infections following open fracture with major extremity trauma, as well as to determine if early antibiotic treatment is associated with lower risk of other adverse events, such as nonunion or wound complications.