Antimicrobial Surgical Prophylaxis

Surgical site infections (SSIs) are the most frequent cause of hospital-acquired infections in surgical patients [1]. Such infections are among the leading causes of postoperative mortality and morbidity [1]. Definitive evidence supporting the use of perioperative antimicrobial prophylaxis (AP) has emerged in recent years [2]. Studies have shown AP to reduce the incidence of SSIs by up to 50% [1]. Key factors to consider in AP are medication type, dosing, duration of prophylaxis, and the timing of administration [1].

Single-shot first-generation or second-generation cephalosporins are widely used as the drug of choice for routine AP [3]. Cefazolin is the most popular cephalosporin chosen for AP due to its excellent safety profile and bactericidal activity against common pathogens associated with SSIs [4]. However, for penicillin-allergic patients, physicians historically have avoided cefazolin in favor of clindamycin and vancomycin to avoid potential cross-reactivity [4]. The disadvantages of clindamycin and vancomycin AP include increased risk of SSIs, higher rates of Clostridioides difficile infection, and higher rates of vancomycin-resistant enterococcal infection [4]. Increasing data over the last twenty years have highlighted the safety of cefazolin in penicillin-allergic patients [4]. In a 2001 study involving 413 penicillin-allergic orthopedic patients receiving cefazolin prophylaxis, the researchers found only 1 potential allergic reaction [4]. Similarly, in a 2015 study analyzing 127 pediatric patients with penicillin allergies, only 1 allergic reaction was observed after receiving cefazolin [4]. Other options for AP include metronidazole, which is frequently opted for in abdominal surgeries (such a colorectal surgery) to prevent infection of gram-negative bacilli and anaerobes [1].

Appropriate timing of AP has been shown to reduce incidence of SSIs by reducing the microbial load during surgery and limiting the opportunity for intraoperative infection [8]. The current World Health Organization (WHO) guidelines for the prevention of SSIs call for a timing of less than 120 minutes before incision but recommend that administration be closer to the incision time (<60 minutes before) for antibiotics with a short half-life [3]. This 60-minute preoperative window remains the most widely implemented recommendation on AP timing since it optimizes serum concentrations for the prevention of SSIs [3,5]. It is possible that a more precise timing regimen may be better for specific types of surgery, but this data does not currently exist in the medical literature [5].

In 2016, the WHO recommended immediate discontinuation of AP after surgery [6]. Prior to this recommendation, AP was frequently continued for 24 to 48 hours postoperatively to prevent SSI [6]. A 2020 meta-analysis of 52 randomized controlled trials involving 19,273 participants found data that supported the WHO recommendations [6]. There was no conclusive evidence for a benefit of postoperative continuation of AP in reducing the incidence of SSIs compared to its immediate discontinuation [6]. Instead, continuation of AP postoperatively unnecessarily increases the risk of antibiotic resistance [6].

Administration of AP to prevent SSIs in patients with a higher BMI continues to be a challenge [7]. Elevated BMI is well-known risk factors for development of SSIs, likely due to decreased tissue penetration of prophylactic antibiotics [7]. For this reason, some medical societies, such as the American College of Obstetricians and Gynecologists, have advised a higher prophylactic dose of cefazolin for obese patients undergoing surgery [8].

References 

1. Demirdag, T., Yayla, B., Tezer, H., & Tapısız, A. (2020). Antimicrobial surgical prophylaxis: Still an issue in paediatrics. Journal of Global Antimicrobial Resistance, 23, 224-227. doi:10.1016/j.jgar.2020.09.020 

2. Miranda, D., Mermel, L., & Dellinger, E. (2020). Perioperative antibiotic prophylaxis: surgeons as antimicrobial stewards. Journal of the American College of Surgeons, 231(6), 766-768. doi:10.1016/j.jamcollsurg.2020.08.767 

3. Weber, W., Mujagic, E., Zwahlen, M. et al. (2017). Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial. The Lancet Infectious Diseases, 17(6), 605-614. doi:10.1016/S1473-3099(17)30176-7 

4. Grant, J., Song, W., Shajari, S. et al. (2021). Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital. Surgery. doi:10.1016/j.surg.2021.03.022 

5. Humphreys, H. (2017). Precise timing might not be crucial: when to administer surgical antimicrobial prophylaxis. The Lancet Infectious Diseases, 17(6), 565-566. doi:10.1016/S1473-3099(17)30178-0 

6. de Jonge, S., Boldingh, Q., Solomkin, J. et al. (2020). Effect of postoperative continuation of antibiotic prophylaxis on the incidence of surgical site infection: a systematic review and meta-analysis. The Lancet Infectious Diseases, 20(10), 1182-1192. doi:10.1016/S1473-3099(20)30084-0 

7. Lee, F., Trevino, S., Kent-Street, E., & Sreeramoju, P. (2013). Antimicrobial prophylaxis may not be the answer: Surgical site infections among patients receiving care per recommended guidelines. American Journal of Infection Control, 41(9), 799-802. doi:10.1016/j.ajic.2012.11.021 

8. Lavie, M., Lavie, I., Cohen, A. et al. (2021). Cefazolin prophylaxis in minimally invasive gynecologic surgery–are dosage and timing appropriate? Prospective study using resampling simulation. Journal of Gynecology Obstetrics and Human Reproduction, 50(9), 102154. doi:10.1016/j.jogoh.2021.102154