Intraoperative Redosing of Surgical Antibiotic Prophylaxis in Addition to Preoperative Prophylaxis Versus Single-Dose Prophylaxis for the Prevention of Surgical Site Infection

A Meta-Analysis and GRADE Recommendation

Niels Wolfhagen, MD; Quirine J. J. Boldingh, MD; Mats de Lange, MD; Marja A. Boermeester, MD, PhD; Stijn W. de Jonge, MD


Annals of Surgery. 2022;275(6):1050-1057. 

In This Article

Abstract and Introduction


Objective: The aim of this study was to determine the effect of preoperative surgical antibiotic prophylaxis (SAP) with additional intraoperative redosing compared to single-dose preoperative surgical antibiotic prophylaxis on the incidence of surgical site infections (SSI).

Summary Background Data: Preoperative SAP is standard care for the prevention of SSI. During long surgical procedures, additional intraoperative redosing of SAP is advised, but there is great variability in redosing strategies and compliance rates.

Methods: We performed a systematic search of MEDLINE (PubMed), Embase, CINAHL and CENTRAL on June 25th, 2021 according to PROSPERO registration CRD42021229035. We included studies that compared the effect of preoperative SAP with additional intraoperative redosing to single dose preoperative SAP (no redosing) on SSI incidence in patients undergoing any type of surgery. Two researchers performed data appraisal and extraction of summary data independently. Meta-analyses were stratified per study type. We used a generic inverse variance random-effects model to estimate a pooled odds ratio with corresponding 95% confidence intervals (CIs).

Results: We included 2 randomized controlled trials (RCT) and 8 cohort studies comprising of 9470 patients. Pooled odds ratios for SSI in patients receiving intraoperative redosing compared to those without redosing were 0.47 (95% CI: 0.19–1.16. I 2 = 36%) for RCTs and 0.55 (95% CI: 0.38–0.79, I 2 = 56%) for observational cohorts. There was considerable clinical heterogeneity among antibiotics used and redosing protocols. GRADE-assessment showed overall low certainty of evidence.

Conclusion: Intraoperative redosing of SAP may reduce incidence of SSI compared to a single dose preoperative SAP in any type of surgery, based on studies with considerable heterogeneity of antibiotic regimens and redosing protocols.


Surgical site infections (SSI) are a common postoperative complication associated with increased hospital stay, morbidity and mortality.[1–4] Surgical antibiotic prophylaxis (SAP) is an effective intervention for the prevention of SSI in indicated procedures.[5] However, administration of antibiotics also has a dose and duration dependent association with adverse effects including the emergence of antibiotic resistance.[6] Therefore, SAP strategies aim to be both optimally effective and restrictive on the amount of antibiotics administered. Administration of SAP before incision is advised but postoperative continuation is discouraged.[7–9]

Evidence of the effect of timely preoperative administration of SAP suggest that adequate tissue concentration is needed at the time of incision and throughout the procedure for SAP to be effective.[10–12] Similarly, inadequate antibiotic tissue concentration upon wound closure is associated with increased risk of SSI[13] and the redundancy of postoperative continuation of antibiotics depends on timely preoperatively administration and intraoperative redosing.[14] Tissue concentration depends on pharmacokinetics, pharmacodynamics, the initial dose, and the time passed since the initial dose.[15,16] Long procedure duration or excessive blood loss may decrease antibiotic tissue levels, potentially below effective concentrations.[15,16] Intraoperative redosing of SAP increases tissue concentration and has been suggested during longer procedures or after excessive blood loss to help prevent SSI.[5] There is some clinical evidence to support this hypothesis.[17,18]

Recent guidelines have assessed redosing of SAP either as out of scope,[7] deemed too few randomized trials available for proper analysis and recommendation[8] or recommend to give a repeat dose if the surgical procedure is longer than the half-life of the antibiotic.[9] However, the latter recommendation is presented without support of evidence.[9,19] An earlier guideline on SAP by the American Society of Hospital Pharmacists (ASHP) recommended redosing of SAP in long procedures defined as exceeding 2 half-lives of the antimicrobial agent or procedures with excessive blood loss.[5] Local SAP protocols, such as the American Surgical Care Improvement Programme, also advise redosing of SAP in surgical procedures lasting longer than 2 times the half-life of the antibiotic given.[20,21] Unfortunately, reported compliance is low.[22,23] The conflicting recommendations leave patients and practitioners in uncertainty and inevitably lead to suboptimal care in some cases. To our knowledge no systematic review on the effect of SAP redosing on SSI risk has been performed.

We performed a systematic review and meta-analysis to assess the effect of intraoperative redosing in addition to preoperative SAP compared to a single dose of preoperative SAP on the incidence of SSI. We hypothesized that intraoperative redosing of SAP reduces the risk of SSI.