Antibiotic Prophylaxis in Open Fractures

Evidence, Evolving Issues, and Recommendations

Matthew R. Garner, MD; Saranya A. Sethuraman, MD; Meredith A. Schade, MD; Henry Boateng, MD


J Am Acad Orthop Surg. 2020;28(8):309-315. 

In This Article

Evolving Frontiers in Antibiotic Prophylaxis

Systemic Versus Local Therapy

There are no aggregate data in humans on the efficacy of topical antibiotic therapy without adjunct systemic prophylaxis.[25] A rat femur model of open femur fractures with 25-mg/kg vancomycin powder applied over the fracture site achieved average concentrations of 1.5 mg/g in surrounding muscle, 199 mcg/g in fractured bone, and 1.8 mcg/mL in plasma.[28] The fracture site concentration of vancomycin with topical application exceeded the typical concentration of vancomycin after intravenous (IV) dosing for 48 hours after application and was undetectable after 96 hours. A similar model of open femur fractures showed topical vancomycin is effective in reducing rates of surgical site infection as long as it is applied within 24 hours after injury and that it was present in detectable serum levels in 20% of specimens after 14 days.[29]

In a study of pelvic and acetabular fractures, topical vancomycin powder applied intraoperatively at the time of wound closure led to fewer surgical site infections and no increase in rates of renal failure: The risk of infection was 14.5% and 4.2% (P = 0.04) for the control and treatment groups, respectively.[30] Of note, the rate of infection after application of topical antibiotics was 71% lower in cases with estimated blood loss less than one liter compared with surgeries with a larger estimated blood loss.[30] Unpublished but presented data would suggest that infection rate was also decreased in high-risk fractures, including calcaneus, pilon, and bicondylar tibial plateau, if topical vancomycin was used at the time of definitive fixation and soft-tissue coverage.[31]

Topical application of glycopeptides may avoid systemic adverse effects, and initial in vivo models suggest that topical vancomycin application without systemic prophylaxis may achieve adequate bactericidal tissue concentrations.[28] The use of topical vancomycin is an evolving concept, and preliminary results are promising, but indications for use and dosing remain poorly defined.

Timing of Antibiotic Therapy

Timing of the first dose of antibiotic administration is a priority. Delayed administration of the first dose of antibiotic prophylaxis increases the risk of infection markedly.[32] With only cefazolin as prophylaxis, no deep surgical site infections were seen 90 days after type III open tibia fractures if antibiotics were given within 66 minutes of injury.[33] Seventeen percent of those receiving their first dose of antibiotics after 66 minutes developed deep surgical site infections.[33] This rate was unaffected by patient's smoking, diabetes, age, or injury severity score. There is no change in infection rate with delayed initial surgical treatment in a study of 736 patients;[34] time to surgical débridement is considered to be independent of infection risk as long as débridement is done within 24 hours of injury and gross contamination is not present.[35] Both EAST guidelines and Surgical Infection Society recommend administration of antibiotics as soon as possible.[6,10]

Duration of Therapy

Prolonged antibiotic therapy past 24 hours has not demonstrated a notable decrease in infection risk of open fractures including type III open fractures.[36] A series of 77 type II tibia fractures showed no difference in infection rate between 24 hours and 5 days of antibiotic treatment.[37] Independent of the severity of open fracture, 24 hours of treatment is noninferior to 5 days of treatment with a second-generation cephalosporin in a prospective randomized trial of 248 patients.[38] These findings were echoed in 2015 and 2017 systematic reviews demonstrating no benefit to extended antibiotic treatment.[9,39] EAST currently recommends discontinuing antibiotics 24 hours after wound closure in type I and II injuries regardless of the duration of antibiotic therapy between presentation and definitive surgery.[6] In type III open fractures, EAST recommends antibiotics for 72 hours after injury or 24 hours after soft-tissue coverage is achieved.[6] The Surgical Infection Society also found no evidence for prolonged antibiotic treatment.[10]

Coverage of Resistant Organisms

No additional clinical parameters have been developed to predict whether the microbe causing an infection would have been susceptible to the prophylactic antibiotic given at presentation other than the Gustilo-Anderson injury severity classification.[40] In 2008, a tertiary care institution introduced a new prophylactic regimen that excluded aminoglycosides, vancomycin, and penicillin.[13] In an effort to reduce use of broad-spectrum antibiotics and the resultant selection pressure toward resistant micro-organisms, the authors used only cefazolin for type I and II open fractures (clindamycin for penicillin allergy) and ceftriaxone for type III open fractures (clindamycin and aztreonam for penicillin allergy). They saw no statistically notable change in surgical site infection rates compared across fracture sites or open fracture types. The MRSA infection rate stayed stable at 2.7% after the change from 3.0% before (P = 1.0). Multidrug-resistant organisms (MDROs) constituted 76.2% of preprotocol infections and 72.2% postprotocol infections (P = 1.0). Notably, aminoglycoside and glycopeptide use decreased from 53.5% to 16.4% (P < 0.01).[13]