Timing of Preoperative Antibiotic Prophylaxis and Surgical Site Infection

TAPAS, An Observational Cohort Study

Stijn W. de Jonge, MD, MSc; Quirine J. J. Boldingh, MD; Anna H. Koch, MD; Lidewine Daniels, MD, PhD; Eefje N. de Vries, MD, PhD; Ingrid J. B. Spijkerman, MD, PhD; Wim M. Ankum, MD, PhD; Gino M. M. J. Kerkhoffs, MD, PhD; Marcel G. Dijkgraaf, PhD; Markus W. Hollmann, MD, PhD; Marja A. Boermeester, MD, PhD


Annals of Surgery. 2021;274(4):e308-e314. 

In This Article

Abstract and Introduction


Objective: To test the hypothesis that surgical site infection (SSI) risk differs, after administration of surgical antibiotic prophylaxis (SAP) within 60–30 or 30–0 minutes before incision.

Background: The importance of appropriate timing of SAP before surgery has long been recognized. However, available evidence is contradictive on the best timing within a 60–0 minutes time interval before incision. Here, we aim to evaluate previous contradictions with a carefully designed observational cohort.

Methods: An observational cohort study was conducted in a Dutch tertiary referral center. For 2 years, consecutive patients with SAP indication undergoing general, orthopedic, or gynecologic surgery were followed for the occurrence of superficial and deep SSI as defined by the Center of Disease Control and Prevention. The association between timing of SAP and SSI was assessed using multivariable logistic regression.

Results: After 3001 surgical procedures, 161 SSIs were detected. In 87% of the procedures, SAP was administered within 60 minutes before incision. Only antibiotics with short infusion time were used. Multivariable logistic regression indicated there was no conclusive evidence of a difference in SSI risk after SAP administration 60–30 minutes or 30–0 minutes before incision [odds ratio: 0.82; 95% confidence interval (0.57–1.19)].

Conclusions: For SAP with short infusion time no clear superior timing interval within the 60-minute interval before incision could be identified in this cohort. We were unable to reproduce differences in SSI risk found in earlier studies.


Surgical site infections (SSI) are a dreadful complication in surgery that accounts for 21.8% of all hospital-acquired infections in the United States.[1] SSI increase postoperative morbidity, mortality, and cause up to 1.6 billion dollar in excess healthcare costs every year.[2] Surgical antibiotic prophylaxis (SAP) is invaluable in the prevention of SSI. The relevance of timing of administration has long been recognized and SAP administration shortly before incision is recommended in most professional guidelines.[3–5] However, exactly how close to incision remains subject of debate and was identified as a research gap in the recent World Health Organization guidelines for SSI prevention.[4] Based on the available evidence, no clear superior timing interval within 120 minutes before incision was identified,[4,6] although administration within 60 minutes before incision was advised for antibiotics with shorter half-lives (eg, most cephalosporins).[4]

The available evidence within 60 minutes is contradictive; some observational studies suggest that SAP should be administered within 30 minutes before incision to minimize the risk of SSI,[7,8] whereas others suggest a benefit when administered more than 30 minutes before incision,[9,10] or no difference at all.[11] However, important aspects of the SAP regimen such as the agents used (eg, differences in half-life and infusion time), preoperative antibiotic use, intraoperative redosing, and postoperative antibiotic use were not standardized.[7–10] The contradictive results and methodological limitations of these studies leave practitioners in uncertainty on a proposed risk for their patients. Recently, a large multicenter randomized controlled trial compared early administration of SAP in the anesthesia room to later administration in the operating room and found no difference in SSI risk.[12] However, the actual timing of SAP overlapped between the 2 randomized groups, risking bias towards the null-hypothesis of no effect, and casting doubt on the results.[12] As a result, the uncertainty remains. Here once more, we test the hypothesis that SSI risk after SAP administration within 60–30 minutes before incision differs when compared to SAP administration within 30–0 minutes before incision, but take intraoperative redosing, pre- and postoperative antibiotic use, half-live, and infusion time into account: the timing of surgical antibiotic prophylaxis and surgical site infections study.