“Is Timing Everything?” – A Comparison of β-Lactam vs Non–β-Lactam Prophylaxis in Elective Colorectal Surgery

Reviewed by: David Cluck, PharmD; East Tennessee State University

Collins and colleagues evaluated whether guideline-concordant antibiotic timing and dose optimization had any effect on 30-day surgical site infections (SSIs) in patients undergoing elective colorectal surgery.1 The authors cited previous studies examining differences in SSIs between β-lactam and non–β-lactam alternatives have not controlled for technical aspects such as dosing and timing of surgical prophylaxis.2,3 Surgical prophylaxis regimens were stratified by β-lactam regimens and non–β-lactam regimens. This multicenter cohort from the Michigan Surgical Quality Collaborative included 20,140 elective colorectal procedures in adult patients between July 2012 and June 2021. Within the cohort, approximately 90% of patients received β-lactam prophylaxis compared to 10% who received non–β-lactam alternative prophylaxis. Patients in the β-lactam cohort were more likely to receive guideline-concordant antibiotic dosing (15,124 [83.6%] vs 1,084 [53.1%]; P < .001), guideline-concordant timing (16,946 [93.6%] vs 1,707 [83.6%]; P < .001), or combined guideline-concordant dose and timing (14,216 [78.6%] vs 751 [36.8%]; P < .001), and had fewer SSIs (1114 [6.2%] vs 172 [8.4%]; P < .001). After adjusting for confounders, use of β-lactam surgical prophylaxis was associated with a lower risk of SSIs (ARR, 0.74; 95% CI, 0.63-0.87; P < .001).

Interestingly, ertapenem (ARR, 1.20; 95% CI, 1.02-1.40; P = .03), cefoxitin (ARR, 1.16; 95% CI, 1.00-1.34; P = .047), clindamycin and aminoglycoside (ARR, 1.64; 95% CI, 1.29-2.08; P < .001), metronidazole and aminoglycoside (ARR, 1.61; 95% CI, 1.07-2.41; P = .02), and clindamycin and fluoroquinolones (ARR, 2.06; 95% CI, 1.29-3.30; P = .002) were associated with increased SSIs compared with cefazolin and metronidazole.

This study concluded that neither guideline-concordant dosing (ARR, 1.04; 95% CI, 0.91-1.20; P = .54) nor timing (ARR, 1.13; 95% CI, 0.92-1.38; P = .25) were associated with increased SSI risk.1 However, β-lactam prophylaxis continues to demonstrate a reduction in SSI risk when compared to alternative prophylactic regimens. This was recently exemplified in a large Swiss cohort study conducted by Largiadèr and colleagues who showed use of a non–β-lactam surgical prophylactic regimen was associated with 1.8-fold higher odds of surgical site infection.4 Moreover, a recently published systematic review and network meta-analysis also reinforced the findings by Collins et al. in patients undergoing elective colorectal surgery.5

References:

  1. Collins CD, Hartsfield E, Cleary RK, Veve MP, Brockhaus KK. β-Lactam vs Non-β-Lactam Prophylaxis in Elective Colorectal Surgery. JAMA Netw Open. 2026 Apr 1;9(4):e266708. 
  2. Blumenthal KG, Ryan EE, Li Y, Lee H, Kuhlen JL, Shenoy ES. The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk. Clin Infect Dis. 2018 Jan 18;66(3):329-336.
  3. Lam PW, Tarighi P, Elligsen M, Gunaratne K, Nathens AB, Tarshis J, Leis JA. Self-reported beta-lactam allergy and the risk of surgical site infection: A retrospective cohort study. Infect Control Hosp Epidemiol. 2020 Apr;41(4):438-443. 
  4. Largiadèr S, Berthod D, Widmer A, Troillet N, Jackson H, Perdrieu C, Harbarth S, Sommerstein R; Swissnoso Group. β-Lactam vs Non-β-Lactam Antimicrobial Prophylaxis and Surgical Site Infection. JAMA Netw Open. 2025 Oct 1;8(10):e2540809. 
  5. Motaghi S, Karam SG, Mulazzani F, Mirzayeh Fashami F, Buchan TA, Ibrahim S, Moradi Falah Langeroodi S, Khademioore S, Couban RJ, Mbuagbaw L, Mertz D, Loeb M. Antibiotic Prophylaxis Strategies and Surgical Site Infections in Colorectal Surgery: A Systematic Review and Network Meta-Analysis. JAMA Netw Open. 2026 Feb 2;9(2):e2560095.