Perioperative and Postoperative Antibiotics - Systemic and Local
In patients with major extremity trauma undergoing surgery, it is recommended that antibiotic prophylaxis with systemic cefazolin or clindamycin be administered, except for Type III (and possibly Type II) open fractures, for which additional Gram-negative coverage is preferred.
Prevention of Surgical Site Infection After Major Extremity Trauma (2022)
This guideline was produced in collaboration with METRC, with funding provided by the US Department of Defense. Endorsed by: ASES, POSNA, AOFAS, IDSA, OTA


In patients with major extremity trauma undergoing surgery, antibiotic prophylaxis with systemic cefazolin or clindamycin is recommended over expanded Gram-negative coverage, although for Type III fractures, piperacillin-tazobactam is preferred. The addition of gentamicin or vancomycin to cefazolin does not appear to be helpful. In closed and open fractures (except Type III and possibly Type II open fractures), there is no need to continue antibiotic prophylaxis longer than a day. Local antibiotic delivery prophylaxis appears to be promising, with one high quality study (O’Toole 2021) finding that peri-operative vancomycin powder may be useful for decreasing Gram-positive infections in closed fractures. Implant protection was also identified as being promising for prevention of surgical site infection, with one study (Pinto 2019) demonstrating a benefit for gentamicin coated nails; tobramycin-impregnated beads (Osterman 1995) also appeared promising.

Two high (Mathur 2013, Vasenius 1998), five moderate (Crist 2018, Dunkel 2013, Janmohammadi 2011, Saveli 2013, Sorger 1999), and seven low quality articles (Lloyd 2017, Frantz 2020, Bankhead-Kendall 2019, Lachman 2018, Pannell 2016, Patanwala 2019, Stennett 2020) informed the recommendation for antibiotic prophylaxis, and one high (O’Toole 2021), two moderate (Moehring 2000, Pinto 2019) and four low quality articles (Qadir 2020, Singh 2015, Vaida 2020, Osterman 1995) informed the recommendation for local prophylactic strategies. Lloyd (2017) evaluated narrow spectrum (cefazolin, clindamycin or amoxicillin-clavulanate) compared to expanded
Gram-negative coverage (included fluoroquinolone and/or aminoglycoside) for combat-related open fracture injuries reporting a beneficial effect of the latter for skin and soft-tissue infections, with no difference in osteomyelitis, length of hospitalization, or operating room visits. A higher proportion of patients in the expanded Gram-negative coverage group had Gram-negative organisms isolated that were not susceptible to fluoroquinolones and/or aminoglycosides. The authors concluded that their results support the use of cefazolin or clindamycin with open fractures.

Sorger (1999) evaluated the response to either gentamicin 5 mg/kg divided into two daily doses or gentamicin 6 mg/kg once daily, both in combination with cefazolin 1g/8hours for open tibial, ankle, forearm, femur, humerus, foot, and patella fracture, revealing no differences in infection rates.

Vasenius (1998) evaluated the response to peri-operative clindamycin versus cloxacillin for open clavicle, upper arm, elbow, forearm, wrist/hand, finger, femur, knee, lower leg, ankle, foot, toe, talus or calcaneus fracture, with the former being more beneficial with regards to total infection rates. Neither clindamycin nor cloxacillin demonstrated high efficacy in Type III open fractures.

Frantz (2020) compared intravenous cefazolin and aminoglycoside to piperacillin-tazobactam for Gustilo type II or III open fractures of the extremities. Compared to piperacillin-tazobactam, both cefazolin-based regimens had higher risks of delayed wound healing or superficial infection. Compared to piperacillintazobactam, cefazolin alone had higher independent odds of deep infection requiring return to the operating room.

Janmohammadi (2011) compared cefazolin with gentamicin to cefazolin with ciprofloxacin for open type IIIA open humerus, radius, ulnar, femur, tibia, and fibula fractures, reporting no difference in efficacy for infection prevention.

Dunkel (2013) evaluated reduced versus extended post-operative antibiotic durations in open fractures (Gustilo and Anderson grade I, II and III and unclassifiable). Overall, compared with one day of antibiotic treatment, two to three days, four to five days or > five days did not exhibit any significant differences in the infection risk. Cefuroxime was the most frequently prescribed antibiotic in this study, although 40 different antibiotic regimens were used.

Saveli (2013) performed a pilot randomized clinical safety study evaluating prophylactic antibiotics in open fractures. Patients were randomized to receive cefazolin alone or vancomycin and cefazolin from presentation to the emergency department until 24 hours after the surgical intervention. There was no difference in the rates of surgical site infections between the study arms.

Mathur (2013) randomly allocated patients to receive three doses of intravenous cefuroxime perioperatively versus 5 days of intravenous cefuroxime with amikacin followed by oral cefuroxime until suture removal for open reduction and internal fixation of closed fractures of limbs reporting no difference in surgical site infection rates.

Lachman (2018) evaluated intravenous cefazolin or vancomycin compared to oral cephalexin or clindamycin for closed ankle fractures with no differences noted.

Crist (2018) performed a randomized study of 23 hours of prophylactic post-operative cefazolin compared to placebo after open reduction internal fixation of closed extremity fractures with no differences in surgical site infections between the two groups.

One open label randomized clinical trial (O’Toole 2021) evaluated intrawound vancomycin powder compared controls for adults with an operatively treated tibial plateau or pilon fracture. The probability of deep infection was lower in the vancomycin powder than the control group with the effect of vancomycin powder attributed to its reduction against Gram-positive but not Gram-negative infections.

Osterman (1995) evaluated tobramycin-impregnated beads compared to no tobramycin-impregnated beads for patients with severe open fractures, with all patients receiving intravenous tobramycin, penicillin and cefazolin, to prevent surgical site infection post-surgery reporting a reduced overall infection rate with the use of tobramycin-impregnated beads. Both acute infection and local osteomyelitis were decreased with the use of tobramycin-impregnated beads, but this was statistically significant only in Gustilo type-3B and type-3C fractures for acute infection, and only in type-II and type-IIIB fractures for chronic osteomyelitis.

Moehring (2000) performed a randomized prospective clinical trial in patients with open fractures comparing tobramycin-impregnated beads versus intravenous antibiotics demonstrating no differences between the groups. Pinto (2019) evaluated gentamicin-impregnated intramedullary interlocking nails versus controls in Gustilo type I and II open tibia fractures reporting a beneficial effect in terms of reduced surgical site infection.

A limitation is that data on several possible alternative antibiotics, that might be considered for prophylaxis, was unavailable. Clindamycin is not favored by some guidelines.

Benefits/Harms of Implementation
The potential benefit is prevention of infection. The potential harms of antibiotic administration include allergy (including anaphylaxis), microbiome disturbances, Clostridioides difficile infection and selection for antibiotic resistance.

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

Cost Effectiveness/Resource Utilization
The cost of peri-operative and post-operative, prophylactic antibiotic(s) is significantly less than what is required for subsequent treatment of infection should it occur.

Future Research
Future research is needed to further refine the ideal peri-operative and post-operative, prophylactic antibiotic(s) best prevent SSI post-surgery.