What are current recommendations for preventing surgical site infections in patients with trauma?

Introduction

Surgical site infections cause substantial healthcare burden, and preventing these infections is an important health-related priority. Postsurgical infections in patients who have experienced major extremity trauma are particularly complicated due to the potential for unique pathogens and a prolonged healing process compared to other surgical wounds, and fracture- and surgery-related infections are more common in patients with trauma than those undergoing planned orthopedic procedures.¹ The precise incidence and prevalence of major extremity trauma cannot be determined since this is an umbrella term for many conditions (eg, open fractures, major/high energy closed fractures, gunshot injuries, crush injuries, blast injuries). According to recent estimates, surgical site infection occurs in up to 27% of severe open fractures.² Fracture-related infections can be recurrent and lead to amputation in up to 9% and 5% of cases, respectively. In some cases, the infection cannot be fully treated and requires long-term antibiotic therapy. Other complications include negative long-term functional outcomes, disability, negative economic effects, and decreased quality of life.¹

Prevention of surgical site infection for most types of surgery are addressed in the now-archived guideline on antimicrobial prophylaxis for surgery authored by the American Society of Health-System Pharmacists, Infectious Diseases Society of America, the Society for Healthcare Epidemiology and of America, and the Surgical Infection Society.³ One of the clinical scenarios not addressed in this guideline was surgical wounds related to trauma. To address the longstanding need to define optimal antimicrobial prophylaxis in patients undergoing post-trauma surgery, in 2022 the American Association of Orthopedic Surgeons (AAOS) published a guideline on preventing surgical site infection after major extremity trauma.^1,2 This article aims to summarize the antimicrobial recommendations from the guideline.

Guideline recommendations
The AAOS makes several different types of conclusions after reviewing the available literature.¹ They provide ‘recommendations’ for clinical questions with good evidential support (ie, at least 2 moderate or high-quality studies) and ‘options’ for clinical questions with limited, lacking, or conflicting evidence. Table 1 summarizes the pharmacotherapy-focused AAOS guideline recommendations.

In addition to these pharmacologic recommendations, the guideline also states that perioperative nasal and skin decolonization can be considered (strength of evidence: consensus [based on clinical opinion]; reliable evidence on the topic was lacking).¹ Nasal Staphylococcus aureus decolonization with mupirocin nasal ointment is suggested with an individualized risk/benefit assessment due to a lack of definitive evidence of efficacy. Evidence is also lacking to support the use of chlorhexidine for full-body cleansing, but the guideline supports the practice of full-body washing with plain or antiseptic soap. Preoperative surgical skin preparation should be accomplished with an alcohol-based solution.

Literature summary
Cefazolin and clindamycin are well-established for surgical infection prophylaxis.³ However, the other drug-focused recommendations in the AAOS guideline are less familiar and may warrant further discussion.

Gram-negative coverage for Type III fractures
There is growing evidence that gram-negative organisms are present in trauma-related fractures. In 2022, the Trauma Infectious Disease Outcomes Study group published a review of 8,300 isolates from U.S. military hospitals from 2009 to 2014.⁴ At admission, 12% of injured military personnel were colonized with multidrug resistant gram-negative bacilli (commonly Escherichia coli and Enterococcus), and 61% of combat-related wound infections were polymicrobial (including gram-negative organisms). Although this is a unique population, this data underscores the potential for gram-negative colonization/infection in traumatic wounds.

The guideline recommendation for prophylaxis with gram-negative coverage for Type III open fractures is mainly supported by a retrospective review of 202 patients with Type II or III open fractures who received surgical prophylaxis with either cefazolin, cefazolin plus aminoglycoside, or piperacillin-tazobactam.⁵ After adjusting for confounding variables, the odds of delayed wound healing or superficial infection requiring oral antibiotics was higher with cefazolin (OR, 3.35; 95% CI, 1.43 to 7.85; p=0.005) and cefazolin plus aminoglycoside (OR, 2.49; 95% CI, 1.01 to 6.14; p=0.047) compared to piperacillin-tazobactam. This led to increased risk of return to the operating room with cefazolin (OR, 3.65; 95% CI, 1.38 to 9.67; p=0.009) compared to piperacillin-tazobactam.

Local antibiotic delivery

The most recent evidence for local antibiotic delivery is a 2022 meta-analysis of 7 studies (n=3593) of intraoperative topical antibiotics during orthopedic surgery for pelvic and lower limb trauma.⁶ There was no difference in the odds of developing a deep surgical site infection with topical antibiotics compared to IV antibiotics alone (OR, 0.77; 95% CI, 0.52 to 1.13; p=0.18; I²=22%). The highest-quality study in the meta-analysis was also evaluated for the AAOS guideline. It was an RCT in 980 patients who received intra-wound vancomycin powder (1000 mg) plus usual care or usual care alone during tibial fracture fixation surgery.⁷ About 20% of patients in each group had open fractures. The authors found a significant reduction in deep surgical site infection in the treatment group compared to the control group (6.4% vs. 9.8%; p=0.06), which was mainly due to fewer infections with gram-positive organisms. Other outcomes (superficial infection, nonunion, wound dehiscence) were similar between groups. A post-hoc analysis of this study reported that none of the patients had detectable serum vancomycin levels.⁸

A systematic review of 8 studies (n=203) reported high rates of bone healing and no adverse effects among patients who received gentamicin-coated tibia nails during primary fracture fixation and revision surgeries (94% and 88%, respectively).⁹ A small randomized trial (n=28) reported significantly fewer surgical site infections among patients with Type I or II open tibia fractures who received gentamicin-coated nails compared to regular nails (p=0.031).¹⁰ The efficacy of aminoglycoside beads added to systemic therapy is also supported by a retrospective study.¹¹

Conclusion

The AAOS guideline on preventing surgical site infections in patients with major extremity trauma provides needed guidance for clinical practice. Many of the guideline recommendations are supported by high-quality data but further prospective and real-world studies will bring further clarity about optimal strategies for preventing these infections and their subsequent complications.

References

1. American Academy of Orthopaedic Surgeons. Prevention of Surgical Site Infections After Major Extremity Trauma Evidence-Based Clinical Practice Guideline. https://www.aaos.org/globalassets/quality-and-practice-resources/dod/ssitrauma/ssitraumacpg.pdf. Published March 22, 2022. Accessed June 22, 2022.
2. Iliadis AD, Shivji F, Debuka E, Trompeter A, Narayan B, Heidari N. Current concepts in the prevention, diagnosis and treatment of fracture-related infection (FRI). Eur J Orthop Surg Traumatol. 2021;31(5):957-966. doi:10.1007/s00590-021-02956-8
3. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568
4. Mende K, Akers KS, Tyner SD, et al. Multidrug-Resistant and Virulent Organisms Trauma Infections: Trauma Infectious Disease Outcomes Study Initiative. Mil Med. 2022;187(Suppl 2):42-51. doi:10.1093/milmed/usab131
5. Frantz TL, Everhart JS, Kanney JM, et al. Early complications of antibiotic prophylaxis with cefazolin protocols versus piperacillin-tazobactam for open fractures: A retrospective comparative study. Current Orthopaedic Practice. 2020;6:549-555.
6. Ma N, Gogos S, Moaveni A. Do intra-wound antibiotics reduce the incidence of surgical site infections in pelvic and lower limb trauma surgery? A systematic review and meta-analysis. J Orthop Trauma. 2022;10.1097/BOT.0000000000002422. doi:10.1097/BOT.0000000000002422
7. Major Extremity Trauma Research Consortium (METRC), O’Toole RV, Joshi M, et al. Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial. JAMA Surg. 2021;156(5):e207259. doi:10.1001/jamasurg.2020.7259
8. O’Toole RV, Degani Y, Carlini AR, et al. Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery. J Orthop Trauma. 2021;35(1):29-34. doi:10.1097/BOT.0000000000001866
9. De Meo D, Cannari FM, Petriello L, Persiani P, Villani C. Gentamicin-Coated Tibia Nail in Fractures and Nonunion to Reduce Fracture-Related Infections: A Systematic Review. Molecules. 2020;25(22):5471. doi:10.3390/molecules25225471
10. Pinto D, Manjunatha K, Savur AD, Ahmed NR, Mallya S, Ramya V. Comparative study of the efficacy of gentamicin-coated intramedullary interlocking nail versus regular intramedullary interlocking nail in Gustilo type I and II open tibia fractures. Chin J Traumatol. 2019;22(5):270-273. doi:10.1016/j.cjtee.2019.03.006
11. Ostermann, Peter, Seligson, David, Henry, Stephen. Local Antibiotic Therapy for Severe Open Fractures: A Review of 1085 Consecutive Cases. J Bone Joint Surg Br. 1995;77-B(1):93-97. Cited in: Journals@Ovid Full Text at http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=ovftb&NEWS=N&AN=00004624-199501000-00018. Accessed July 12, 2022.

Prepared by:
Heather Ipema, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist

Erika Maslennikov
Alexandra Wierzbiak
PharmD Candidates Class of 2025

August 2022

The information presented is current as of July 11, 2022. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.