Open Breaks - Antibiotics for Open Fractures

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Open fractures are a common pathology seen in emergency departments, especially in trauma centers. In open fractures, the skin barrier has been compromised, exposing sterile bone to the environment. Considered a true orthopedic emergency, these fractures have high morbidity due to osteomyelitis, with infection rates up to 55%. (1) Appropriate and timely intervention in the emergency department with proper antibiotic therapy, wound care, and early orthopedic surgery involvement dramatically reduces the risk of developing osteomyelitis. In this post we will discuss antibiotic recommendations for osteomyelitis prophylaxis for open fractures. Initial management of open fractures is discussed in another post. 

Empiric Antibiotics

            As part of their initial study, Gustilo and Anderson (creators of the Gustilo-Anderson open fracture classification system) obtained wound cultures from each open fracture. (2) The resulting antibiotic sensitives informs the antibiotics we use today for empiric treatment. Ultimately, first generation cephalosporins were determined to have good antimicrobial coverage for all three injury grades, particularly grades I/II. In the 1986 study, Gustilo recommended the addition of an aminoglycoside to the treatment regimen for grade III fractures only, preferably gentamicin, extending the gram-negative coverage. (3) As a result of these studies, the following antibiotic regimen was proposed: grade I/II fractures receive cefazolin (2 grams IV Q8H) and grade III fractures receive cefazolin (2 grams IV Q8H) + gentamicin (5 mg/kg IV Q24H). This regimen remained largely unchanged through the rest of the 20th century and into the first decade of the 21st century. 

Table 1: Antibiotics for Open Fractures Kyle Schuchter, PharmD Candidate 2021. Edited by: Paige Garber Bradshaw, PharmD, BCCCP

Table 1: Antibiotics for Open Fractures 

Kyle Schuchter, PharmD Candidate 2021. Edited by: Paige Garber Bradshaw, PharmD, BCCCP

Antibiotics should be given as soon as possible. Prompt administration of appropriate antibiotics has been shown to drastically reduce the incidence of osteomyelitis. From the literature, approximately 20% of the fractures that receive antibiotics later in their course developed osteomyelitis. In contrast, 5% of fractures that received antibiotics early in their course developed osteomyelitis. Due to the patient’s overall stability, need for transport to a referral center, and other factors, it may not be possible for the patient to undergo surgery in the desired 8 hours after their injury. (4) Much research has been conducted in the realm of orthopedics to determine the optimal timing of surgery. They found that surgical intervention in the first 24 hours is necessary, preferably in the first 8 hours, provided there were no complicating factors such as vascular injury. However, timing of surgery had less impact on preventing infection than administration of antibiotics in the first hour(s) after injury. (5) Thus, it is imperative that emergency physicians provide appropriate antibiotics expeditiously to provide the patient the best protection against developing infectious complications. 

Duration of therapy is dependent on the Gustilo-Anderson classification. Grades I/II receive 24 hours of IV antibiotics. Grade III should receive 72 hrs of IV antibiotics or antibiotics through the first 24 hrs after definitive closure of the wound. Longer courses of antibiotics have not shown any additional infection prophylaxis and can lead to the development of drug resistant organisms as well as increase the risk of side effects (drug interactions, organ toxicity, etc). (6) 

Initial wound cultures are of minimal utility. The initial cultures are typically polymicrobial and rarely change the antibiotic regimen. Furthermore, in patients that ultimately develop infections, the isolated microbe(s) is often different than those seen on the initial wound culture. Thus, wound cultures are beneficial if a patient develops infection after successfully completing the standard open fracture empiric antibiotic regimen but are of minimal utility in the initial setting. (7) 

            In the last decade, desires for antimicrobial stewardship and concern over the side effects of gentamicin (nephrotoxicity in particular) has prompted clinicians to study alternative antibiotic regimens. Unfortunately, many of the alternative regimens studied either carried additional side effects, increased infection rates, or required additional antibiotics to achieve the same infection control. In 2014, the University of Michigan published a study proposing ceftriaxone monotherapy (2 grams IV Q24H) for grade III fractures. Ceftriaxone was chosen due to its broad gram-positive and gram-negative coverage and its long duration of action. This single center, prospective/retrospective study enrolled 174 open tibia/fibula fractures and monitored rates of infection in grade III fractures with the standard antibiotic therapy (1st gen cephalosporin + aminoglycoside) vs ceftriaxone monotherapy. Ultimately, no significant increase in infection rate was observed between the two groups (p = 0.58). (8) Based on this study, ceftriaxone monotherapy has been embraced in recent years as an acceptable alternative to the standard dual therapy for grade III fractures. (1,9,10,11) 

In cases of beta lactam hypersensitivity, acceptable alternative regimens must cover the bacteria indicated in the fracture’s Gustilo-Anderson grade. Recommendations vary across the literature. (1,2) For grade I/II fractures, vancomycin (loading dose of 20-30 mg/kg with maintenance doses 10-15 mg/kg Q8-12H) or clindamycin (900 mg IV Q8H) are proposed. For grade III fractures, clindamycin (900 mg IV Q8H) is classically recommended, (2) but newer literature proposes aztreonam (2G IV Q8H) with vancomycin (1 gram IV Q12H). (1) Given the varying recommendations, a discussion with your pharmacist may be warranted.  

Environmental Wound Contamination 

            Environmental contaminants require broadening of antibiotic coverage to account for atypical bacteria. Fresh water sources expose the wound to Pseudomonas and Aeromonas, necessitating pseudomonal coverage. Piperacillin/Tazobactam (4.5 grams IV Q8H) is the preferred regimen. Saltwater sources expose the wound to vibrio species. Doxycycline has excellent specificity against vibrio and is the antibiotic of choice. However, doxycycline cannot be administered as a monotherapy as it lacks sufficient broad coverage. Combination therapy of doxycycline (100 mg IV IV/PO Q12H) with Piperacillin/Tazobactam (4.5 grams IV Q8H) provides excellent coverage for the major water borne bacteria. (1,10,11) 

            Open fractures with soil or fecal contamination raise concern for exposure to clostridium and anaerobic organisms. Metronidazole (500 mg IV Q8H) is the recommended therapy, but a high dose penicillin is also acceptable. (1,9,10,11)

Irrigation/Debridement 

In conjunction with antibiotics, open fractures require irrigation and debridement to prevent osteomyelitis. While these fractures typically undergo washout in the OR, this can be delayed by several hours. Early irrigation and removal of gross contaminants/foreign bodies significantly reduces the risk of osteomyelitis by physically removing the microbes and other niduses for infection from the wound. Obvious contaminants (plant material, dirt, inorganic foreign bodies) should be removed. Low pressure wound irrigation in the emergency department carries minimal risk of further injury with the benefit of early bacterial count reduction in the affected tissues. High pressure irrigation is not recommended initially due to the risk of tissue injury and the risk of forcing contaminants deeper into the wound. Normal saline is the irrigant of choice. It is inexpensive, readily available in the emergency department, and has been shown to be equivalent to fluids with added antimicrobial agents or soaps for initial wound irrigation. Gravity assisted low-pressure lavage with normal saline (normal saline bags suspended from an IV pole, open to gravity, attached to large bore IV tubing) is an easy-to-use method with adequate results until definitive washout and debridement are performed in the OR. (12) The wound should be covered with sterile gauze soaked in sterile saline to prevent further contamination.  

Tetanus

The mechanism of injury and contaminants frequently found in open fractures increases the patient’s risk of tetanus infection. Open fractures, puncture wounds, wounds contaminated by organic material and foreign bodies have a high risk for tetanus. As such, all patients with open fractures need their tetanus vaccination status assessed and updated as needed. In patients without previous tetanus vaccination, tetanus immunoglobulin should be administered in addition to the tetanus toxoid (preferably the Tdap) with plans to complete the immunization series. Previously vaccinated patients who have not received a booster in more than five years should receive the tetanus toxoid only. Previously vaccinated patients who received the booster in the last five years do not require a booster. (13,14) 

Conclusion

            Open fractures are a common pathology seen in emergency departments that can result in high morbidity. Though definitive management of these injuries is provided by our orthopedic surgery colleagues, appropriate management in the emergency department can significantly reduce the complication patients experience from open fractures.  

References 

  1. Garner MR, Sethuraman SA, Schade MA, Boateng H. Antibiotic Prophylaxis in Open Fractures: Evidence, Evolving Issues, and Recommendations. J Am Acad Orthop Surg. 2020 Apr 15;28(8):309-315. doi: 10.5435/JAAOS-D-18-00193. PMID: 31851021. 

  2. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am. 1976 Jun;58(4):453-8. PMID: 773941.

  3. Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative to treatment and results. Orthopedics. 1987 Dec;10(12):1781-8. PMID: 3324085.

  4. Malhotra AK, Goldberg S, Graham J, Malhotra NR, Willis MC, Mounasamy V, Guilford K, Duane TM, Aboutanos MB, Mayglothling J, Ivatury RR. Open extremity fractures: impact of delay in operative debridement and irrigation. J Trauma Acute Care Surg. 2014 May;76(5):1201-7. doi: 10.1097/TA.0000000000000205. PMID: 24747449.

  5. Harley BJ, Beaupre LA, Jones CA, Dulai SK, Weber DW. The effect of time to definitive treatment on the rate of nonunion and infection in open fractures. J Orthop Trauma. 2002 Aug;16(7):484-90. doi: 10.1097/00005131-200208000-00006. PMID: 12172278.

  6. Wilkins J, Patzakis M. Choice and duration of antibiotics in open fractures. Orthop Clin North Am. 1991 Jul;22(3):433-7. PMID: 1852421.

  7. Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop Relat Res. 1997 Jun;(339):71-5. doi: 10.1097/00003086-199706000-00010. PMID: 9186203.

  8. Rodriguez L, Jung HS, Goulet JA, Cicalo A, Machado-Aranda DA, Napolitano LM. Evidence-based protocol for prophylactic antibiotics in open fractures: improved antibiotic stewardship with no increase in infection rates. J Trauma Acute Care Surg. 2014 Sep;77(3):400-7; discussion 407-8; quiz 524. doi: 10.1097/TA.0000000000000398. PMID: 25159242.

  9. Hauser CJ, Adams CA Jr, Eachempati SR; Council of the Surgical Infection Society. Surgical Infection Society guideline: prophylactic antibiotic use in open fractures: an evidence-based guideline. Surg Infect (Larchmt). 2006 Aug;7(4):379-405. doi: 10.1089/sur.2006.7.379. PMID: 16978082.

  10. Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures. Cochrane Database Syst Rev. 2004;(1):CD003764. doi: 10.1002/14651858.CD003764.pub2. PMID: 14974035.

  11. Hoff WS, Bonadies JA, Cachecho R, Dorlac WC. East Practice Management Guidelines Work Group: update to practice management guidelines for prophylactic antibiotic use in open fractures. J Trauma. 2011 Mar;70(3):751-4. doi: 10.1097/TA.0b013e31820930e5. PMID: 21610369.

  12. FLOW Investigators, Bhandari M, Jeray KJ, Petrisor BA, Devereaux PJ, Heels-Ansdell D, Schemitsch EH, Anglen J, Della Rocca GJ, Jones C, Kreder H, Liew S, McKay P, Papp S, Sancheti P, Sprague S, Stone TB, Sun X, Tanner SL, Tornetta P 3rd, Tufescu T, Walter S, Guyatt GH. A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds. N Engl J Med. 2015 Dec 31;373(27):2629-41. doi: 10.1056/NEJMoa1508502. Epub 2015 Oct 8. PMID: 26448371.

  13. Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, Clark TA. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018 Apr 27;67(2):1-44. doi: 10.15585/mmwr.rr6702a1. PMID: 29702631; PMCID: PMC5919600.

  14. Havers FP, Moro PL, Hunter P, Hariri S, Bernstein H. Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccines: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2019. MMWR Morb Mortal Wkly Rep. 2020 Jan 24;69(3):77-83. doi: 10.15585/mmwr.mm6903a5. PMID: 31971933; PMCID: PMC7367039.

Authorship

Written by: Kelly Tillotson, MD, PGY-1 University of Cincinnati Department of Emergency Medicine

Peer Review and Editing: Jeffery Hill, MD MEd