Skip to main content
Annals of Gastroenterological Surgery logoLink to Annals of Gastroenterological Surgery
. 2024 Oct 18;9(2):369–378. doi: 10.1002/ags3.12866

Intraoperative redosing of antibiotics for prevention of surgical site infections: A systematic review and meta‐analysis

Yuki Hanai 1,, Jun Hirai 2, Masahiro Kobayashi 3, Kazuhiro Matsuo 1, Keita Kouzu 4, Hiroji Shinkawa 5, Seiichi Shinji 6, Motomu Kobayashi 7, Yuichi Kitagawa 8, Chizuru Yamashita 9, Yasuhiko Mohri 10, Hiroshi Nobuhara 11, Katsunori Suzuki 12, Junzo Shimizu 13, Motoi Uchino 14, Seiji Haji 15, Masahiro Yoshida 16, Toru Mizuguchi 17, Toshihiko Mayumi 18, Yuko Kitagawa 19, Hiroki Ohge 20
PMCID: PMC11877348  PMID: 40046532

Abstract

Background

Appropriate antibiotic prophylaxis is essential for preventing surgical site infections (SSI); however, the clinical benefit of intraoperative redosing remains unclear and controversial owing to insufficient reliable evidence. Therefore, we performed a systematic review and meta‐analysis to assess the effectiveness of prophylactic antibiotic redosing in lengthy surgical procedures.

Methods

We systematically searched the PubMed, Cochrane Library, Web of Science, and Ichushi‐Web databases for articles published until 31 December, 2023. We compared the incidence of SSI between patients receiving and not receiving intraoperative redosing of antibiotics in surgeries lasting ≥3 h. Subgroup analyses were conducted across study characteristics. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel random effects model. The risk of bias was assessed using the ROBINS‐I.

Results

Overall, seven observational studies involving 4,671 patients were included. Intraoperative antibiotic redosing significantly reduced the risk of SSI compared with non‐redosing (OR = 0.65, 95% CI = 0.45–0.94, p = 0.02). Subgroup analyses showed that intraoperative redosing decreased SSI risk in studies with a minimum 4‐h operative time, no postoperative antibiotic continuation, and a moderate risk of bias. However, the statistical heterogeneity of the analyses was high among the studies.

Conclusions

Intraoperative redosing with prophylactic antibiotics during lengthy surgeries may be associated with a lower risk of SSI than non‐redosing. Therefore, we recommend intraoperative redosing for surgeries lasting beyond 3–4 h to reduce the risk of infection. Further research is required to clarify the optimal redosing interval, which should be prioritized in future studies.

Keywords: antimicrobial prophylaxis, intraoperative redosing, meta‐analysis, surgical site infection, timing


In this systematic review and meta‐analysis of seven observational studies, intraoperative redosing of prophylactic antibiotics during lengthy surgeries was associated with a significantly lower risk of SSI than non‐redosing. Therefore, for surgeries lasting longer than approximately 3–4 h, we recommend intraoperative redosing to reduce the risk of infection.

graphic file with name AGS3-9-369-g001.jpg

1. INTRODUCTION

Surgical site infections (SSI) are a major contributor to prolonged hospital stays, heightened morbidity and mortality rates, and increased healthcare costs following surgical procedures. 1 , 2 Prevention of SSI requires a comprehensive approach that emphasizes the implementation of standard protocols, including preoperative scrub techniques, preparation of surgical instruments, and the use of sterile barriers and drapes. An essential aspect of this process is administration of appropriate antibiotic prophylaxis. Particularly, in cases of extended surgical procedures, ensuring the redose of antibiotics during surgery is crucial for maintaining effective serum and tissue concentrations throughout the procedure. Pharmacokinetic studies have shown that antibiotics with a short half‐life, such as cefazolin, require repeated intraoperative administration to reduce the risk of SSI. 3 , 4 Additionally, a recent meta‐analysis suggested that a prolonged operative time can increase the likelihood of developing SSI across a broad array of surgical procedures and specialties. 5

Despite higher infection rates associated with longer procedures, the clinical benefits of intraoperative antibiotic redosing remain unclear and controversial. A few observational studies have suggested that the overall risk of SSI was reduced when antibiotic redosing was administered at the recommended interval during surgery. 6 , 7 In contrast, Steinberg et al. reported no statistically significant relationship between antibiotic redosing and SSI risk. 8 However, due to the small sample sizes in these studies, the estimates of the effects were relatively imprecise. Consequently, clinical practice guidelines for surgery usually recommend intraoperative redosing of prophylactic antibiotics based on pharmacokinetic principles rather than clinical benefits; however, there is currently no consensus on this approach. 9 , 10 More recently, specific guidelines by the World Health Organization (WHO) 11 and the Centers for Disease Control and Prevention (CDC) 2 state “no recommendation/unresolved issue” in this regard due to insufficient reliable evidence to assess the benefits and harms of intraoperative redosing of antibiotics for the prevention of SSI. However, these conflicting recommendations leave patients and practitioners uncertain, and compliance with the redosing of prophylactic antibiotics during lengthy surgeries inadequate in many healthcare settings.

Therefore, in the current systematic review and meta‐analysis, we aimed to assess the effectiveness of intraoperative redosing of antibiotics by examining the SSI rates associated with several different antibiotic regimens.

2. METHODS

2.1. Search strategy

We conducted our study following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines. 12 We performed a literature search using four electronic databases: MEDLINE (PubMed), the Cochrane Library (Cochrane Central Register of Controlled Trials—CENTRAL), Web of Science, and Ichushi‐Web (a Japanese search engine of the Japan Medical Abstracts Society) for articles published until 31 December, 2023. We used the following database specific subject headings (such as MeSH terms) and free texts terms to search for potentially eligible studies: (“antibiotic prophylaxis” OR “antimicrobial agent” OR “antibiotic therapy”) AND (“surgical wound infection” OR “surgical site infection” OR “SSI”) AND (“re‐dose” OR “redose” OR “repeat”). Table S1 provides the full search strategy. Additionally, we manually checked the reference lists of relevant original papers and reviews, screened articles in the PubMed “related citations” section, and restricted the search to human studies. No language restrictions were applied in the search.

2.2. Eligibility criteria and study selection

Two reviewers (YH and KM) independently screened the titles, abstracts, and full texts of eligible articles. The predefined inclusion criteria were as follows: (1) original research articles, (2) participants who received antibiotic prophylaxis prior to incision, (3) prolonged duration of surgery, and (4) available data on the incidence of SSI between the intraoperative redosing and non‐redosing (control) arms. Prolonged duration of surgery was defined as operative time lasting ≥3 h after initiation of procedure, based on the previous guidelines. 9 This corresponds to one to two half‐lives of preoperative antibiotics administered prophylactically. Intraoperative redosing was defined as the administration of any intraoperative dose of antibiotics after the initial preoperative antibiotic prophylaxis. There were no restrictions on the redosing protocol with respect to timing and dosage. The exclusion criteria for the studies were as follows: (1) reviews, editorials, research letters, or protocols; (2) non‐human subjects; and (3) lack of a clear distinction between intraoperative and postoperative antibiotic dosing. If multiple papers were derived from the same study, and the same associated events were reported, only the latest published data were included in our primary analysis. In case of incongruence in the reviewers' assessments, a consensus was reached via discussion with a third reviewer.

2.3. Data extraction

For every eligible study identified from the final screening, two reviewers (YH and KM) independently extracted the following information on pre‐tested standard forms: first author, publication year, study design, participant numbers and characteristics, surgery type, wound class following CDC classification, 13 operative time, types of antibiotics used, intraoperative redosing protocol, timing of preoperative antibiotic administration, presence of postoperative antibiotics, outcome definition, and outcome proportion in each arm for dichotomous data or mean and standard deviation (SD) for continuous data. The outcome data were extracted from a dataset that exclusively comprised patients who underwent prolonged surgery. Disagreements regarding specific data between the two reviewers were resolved by discussion with a third reviewer.

2.4. Outcomes and definitions

The primary outcome was the incidence of SSI after receiving preoperative antibiotic prophylaxis in the intraoperative redosing arm compared with the non‐redosing arm. Secondary outcomes included length of hospital stay, mortality, and adverse events related to SSI. Primary and secondary outcomes were defined according to the definitions of each study.

2.5. Risk of bias assessment

Two reviewers (YH and KM) independently assessed the risk of bias in the included studies, as described in the Cochrane Handbook for Systematic Reviews. 14 The Risk of Bias in Nonrandomised Studies of Interventions (ROBINS‐I) tool was used for non‐randomized studies 15 following the detailed guidance and scales provided in the article, which contains seven domains (bias due to confounding, bias in selection of participants in the study, bias in classification of interventions, bias due to deviations from tended interventions, bias due to missing data, bias in measurement of outcomes, and bias in selection of reported results). After the assessment of each domain, the overall risk of bias was determined for each study. Publication bias was assessed using Egger's test and visual inspection of the funnel plot.

2.6. Statistical analysis

We performed a meta‐analysis using Review Manager for Mac (RevMan, Version 5.4, Copenhagen, Denmark; The Nordic Cochrane Center, The Cochrane Collaboration, 2020) and constructed forest plots. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method and a random effects model as an effect size to assess variations between studies and sampling errors within studies. Statistical heterogeneity among studies was assessed using I 2 statistics. I 2 values of ≥50%, 25%–50%, and ≤25% were regarded as strong, moderate, and no heterogeneity, respectively. For sensitivity analysis, the quality of each article was scrutinized, and if a high degree of heterogeneity was detected, an analysis excluding reports that contributed to the heterogeneity was conducted. Considering potential biases regarding the effectiveness of intraoperative redosing, we also conducted subgroup analyses by reanalysing studies that investigated the variables of interest (study design, operative time, antibiotics used, presence of postoperative antibiotic prophylaxis, and overall risk of bias). p‐values were reported with a hypothesis testing set at a two‐tailed significance level of <0.05.

3. RESULTS

3.1. Study characteristics

During our initial search, 2,256 studies were retrieved from the four electronic databases and reference lists, among which 981 duplicate studies were removed (Figure 1). After screening titles and abstracts, 27 studies were selected for full‐text review. Ultimately, seven studies 6 , 7 , 8 , 16 , 17 , 18 , 19 were included in the meta‐analysis, with a sample size of 4,671 participants from five countries.

FIGURE 1.

FIGURE 1

Flowchart of the selection process for the studies included in this analysis.

Table 1 summarizes the key characteristics of the studies included in the analysis. Among the seven articles, studies by Scher et al., 6 Steinberg et al., 8 and de Jonge et al. 19 had prospective cohort designs, while the remaining four had retrospective designs. None of the reviewed studies were RCTs. Five studies were conducted in a mixed population involving various surgical types, while two studies were performed exclusively in patients undergoing cardiac 7 or colorectal 16 surgery. Most studies included surgical procedures with an operative time ≥ 4 h. However, there were some variations in the intraoperative dosing protocols and choice of prophylactic antibiotics. Two studies 6 , 17 and three studies 7 , 8 , 16 set the redose timing to approximately 3 h and 4 h after the initial dose, respectively, and the remaining two studies 18 , 19 described different protocols. Regarding antibiotic prophylaxis, two studies 6 , 7 only used cefazolin, whereas other studies reported several regimens, including cefazolin. Three studies 17 , 18 , 19 defined SSI using the CDC criteria, two studies 7 , 8 used the criteria of the National Nosocomial Infections Surveillance, one study 16 used its own criteria, and the remaining study 6 did not report the criteria. Additionally, two studies 17 , 19 reported superficial/deep SSIs and organ/space SSIs together as SSIs, whereas other studies could not identify which SSIs were included.

TABLE 1.

Characteristics of the studies included in the meta‐analysis.

Author Country Study design No. of patients Surgery type (%) CDC wound class (%) Operative time Intraoperative redosing protocol Prophylactic antibiotics (%) Timing of initial antibiotics Postoperative antibiotics continuation Definition of SSI
Scher 1997 a USA Prospective cohort 296 General, thoracic, urology, otorhinolaryngology (unspecified) N/A ≥3 h 3 h after initial dose Cefazolin (100) 15–30 min No N/A
Zanetti 2001 USA Retrospective cohort 1,548 Cardiac (100) N/A ≥4 h 4 h after initial dose Cefazolin (100) <90 min Yes Modified NNIS criteria
Morita 2005 b Japan Retrospective cohort 96 Colorectal (100)

II (98.5)

III (1.5)

≥4 h 4 h after initial dose

Cefmetazole (43) flomoxef (34)

Cefotiam (18)

Cefazolin (5)

Cefozopran (<1)

<60 min Yes Presence of purulent discharge in the abdominal surgical wound with or without positive bacteriology, within 30 days after surgery
Steinberg 2009 USA Prospective cohort 512

Cardiac (44)

Hysterectomy (18)

Hip/knee arthroplasty (39)

N/A ≥4 h 4 h after start but end of surgery

Cephalosporins (76)

Cephalosporins plus

Vancomycin (13)

Vancomycin (5)

Quinolones (5)

<60 min

Mostly yes

(87.3%)

NNIS criteria
Zhang 2015 b Canada Retrospective cohort 547

Colorectal (46)

Hepatobiliary (54)

I (9)

II (90)

III (1)

IV (<1)

≥4 h Every 3–4 h depending on the antibiotic used Cefazolin, cephazolin plus metronidazole, clindamycin plus gentamicin, metronidazole plus gentamicin (unspecified) N/A No CDC criteria
Bertschi 2019 b Switzerland Retrospective cohort 593 Abdominal, vascular, trauma (unspecified)

I (52)

II (37)

III (11)

≥4 h Any intraoperative administration before wound closure Cefuroxime, cefuroxime plus metronidazole (unspecified)

SSI group:

30 min (15–50) c

non‐SSI group:

35 min (15–55) c

No CDC criteria
de Jonge 2021 b Netherland Prospective cohort 1,079

Gynecology (22)

Visceral (36)

Vascular (7)

Trauma/orthopedic (35)

I (44.8)

II or III (55.2)

≥4 h Exceeding 2 times t1/2 or ≥1500 mL blood loss

Cefuroxime plus

Clindamycin (50)

Cefuroxime (30)

Cefamandole (15)

Others (5)

<120 min No CDC criteria

Abbreviations: CDC, Centers for Disease Control and Prevention; N/A, not available; NNIS, National Nosocomial Infections Surveillance; SSI, surgical site infection.

a

Patients who underwent surgery lasting ≥3 h were considered evaluable for our analysis.

b

Patients who underwent surgery lasting ≥4 h were considered evaluable for our analysis.

c

Data denote median (interquartile range).

3.2. Surgical site infection

All seven studies contributed to comparing the incidence of SSI between the intraoperative redosing and non‐redosing arms. The random‐effects model illustrated that the prophylactic antibiotic redosing during lengthy surgeries significantly lowered SSI risk compared with non‐redosing (OR = 0.65, 95% CI = 0.45–0.94, p = 0.02, I 2  = 51%; Figure 2). Although statistical heterogeneity was high among the included studies, post‐hoc sensitivity analysis demonstrated that the incoherence was eliminated after excluding the studies by Zanetti et al. 7 and de Jonge et al., 19 which had delayed timing of initial prophylactic antibiotics (OR = 0.52, 95% CI = 0.37–0.72, p < 0.0001, I 2  = 0%).

FIGURE 2.

FIGURE 2

Meta‐analysis for surgical site infection including overall studies. CI, confidence interval; M–H, Mantel–Haenszel method; random, random effects model.

In the subgroup analysis, we found that the intraoperative redosing significantly reduced the SSI risk compared with non‐redosing for six studies that reported a minimum operative time of 4 h (OR = 0.70, 95% CI = 0.49–0.99, p = 0.04, I 2  = 49%; Figure 3). Similarly, for four studies with no postoperative continuation of antibiotic prophylaxis (OR = 0.66, 95% CI = 0.44–0.99, p = 0.04, I 2 = 40%; Figure 4), and for three studies with an overall “moderate” risk of bias (OR = 0.57, 95% CI = 0.40–0.81, p = 0.002, I 2  = 0%; Figure 5), intraoperative redosing significantly reduced SSI risk. However, in each subgroup of the prospective study and the studies with cefazolin‐based antibiotic prophylaxis only, intraoperative redosing did not reduce the risk of SSI. The detailed results of the subgroup analyses for SSI risk are summarized in Figure S1. However, no study reported secondary outcomes specified in our meta‐analysis.

FIGURE 3.

FIGURE 3

Meta‐analysis for surgical site infection of studies with a minimum operative time of 4 h. CI, confidence interval; M–H, Mantel–Haenszel method; random, random effects model.

FIGURE 4.

FIGURE 4

Meta‐analysis for surgical site infection of studies with no postoperative continuation of antibiotic prophylaxis. CI, confidence interval; M–H, Mantel–Haenszel method; random, random effects model.

FIGURE 5.

FIGURE 5

Meta‐analysis for surgical site infection of studies with an overall moderate risk of bias. CI, confidence interval; M–H, Mantel–Haenszel method; random, random effects model.

3.3. Risk of bias assessment

The results of the risk of bias assessment are shown in Figure 6. Only three studies had an overall moderate risk of bias, whereas four studies had a serious or critical risk of bias, mainly because they failed to control the domains of confounding factors and the selection of reported results. For the confounding domain, five studies controlled for suspected confounding factors, such as comorbidities and other baseline characteristics; thus, these studies were assessed as having a moderate risk of bias, although some levels of confounding persisted. For the intervention classification and missing data domains, all studies were classified as having a moderate or low risk of bias. However, one to three studies were rated as having a serious risk of bias, considering participant selection, deviations from intended interventions, and the selection of reported result biases, given that the studies failed to provide adequate information for bias assessment.

FIGURE 6.

FIGURE 6

Risk of bias of each study included in this meta‐analysis.

Publication bias was assessed by visually examining the funnel plot of the primary endpoint (Figure S2), and the p‐value of Egger's test (p = 0.012). Consequently, due to the limited number of studies, the funnel plot exhibited significant asymmetry, indicating an apparent risk of publication bias in our meta‐analysis.

4. DISCUSSION

Several studies have emphasized that an additional dose of prophylactic antibiotics during lengthy surgeries is closely associated with the prevention of SSI. 6 , 16 , 18 However, current guidelines for surgical infection lack clear recommendations regarding intraoperative redosing owing to insufficient research on this approach. 2 , 11 Here, we present a systematic review and meta‐analysis evaluating the effectiveness of the intraoperative redosing of antibiotics in patients who underwent surgery lasting ≥3 h. Several antibiotic regimens and types of surgeries were included in this study. Despite several institutions inadequately complying with the redosing protocol owing to limited clinical data, our findings indicate that the redosing of prophylactic antibiotics during lengthy surgeries is significantly associated with favorable outcomes in terms of the risk of SSI. This is consistent with the effectiveness of intraoperative redosing outlined in a previous meta‐analysis by Wolfhagen et al. 20 However, the study had drawbacks, such as a lack of standardization for operative time among the included studies, inclusion of multiple subsets of the same study, and inadequate analysis due to the pooling of divided study populations; thus, it is difficult to appreciate the accuracy and validity of their results. The 2023 practical recommendations for preventing SSI by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Association for Professionals in Infection Control and Epidemiology (APIC) recommend intraoperative redosing after two half‐lives of the administered agent have passed since the initial prophylactic antibiotic administration. 21 This recommendation is based on pharmacokinetic principles and evidence that adequate tissue and plasma concentrations of antibiotics are maintained throughout the surgical procedure to prevent SSI. 22 , 23 Our findings suggest that timely intraoperative redosing of antibiotics could minimize the possibility of SSI in patients undergoing prolonged surgery, while reinforcing the importance of preoperative prophylactic antibiotic first administration.

The subgroup analysis demonstrated a consistent tendency towards a reduction in SSI risk when intraoperative redosing was applied across various study characteristics of interest, while suggesting a slight increase in benefit for studies without postoperative antibiotic continuation. Current guidelines state that after appropriate initial antibiotic prophylaxis and intraoperative redosing, postoperative continuation of antibiotics is unnecessary. 10 , 11 This aligns with our finding that the impact of redose was more significant in studies that did not continue postoperative antibiotic prophylaxis. Additionally, our study population was restricted to patients who underwent surgery ≥3 h. Therefore, the subgroup analysis revealed significant benefits of intraoperative redosing regardless of the minimum operative time. In cases of surgical procedures completed within 3 h, Scher et al. reported that wound infection rates were similar between groups receiving a single dose and double doses of cefazolin. 6 Randomized controlled trials by Colombo et al. 24 and Cuthbertson et al. 25 also found no significant associations with the intraoperative redosing and the incidence of SSI; however, in the former, intraoperative redosing of antibiotics was performed at least 2 h after incision, while in the latter, patients undergoing surgeries lasting ≥3 h accounted for only 14% of the total. These studies suggest that a single dose of preoperative antibiotics is sufficient for surgical prophylaxis when the operation is completed within 3 h. As the operative duration is not an easily modifiable factor, our findings may be particularly applicable to surgeries that exceed this duration.

Survival benefit is consistently regarded as the most important clinical outcome of any perioperative therapeutic intervention. However, it was difficult to draw any relationship between intraoperative redosing and survival in our analysis owing to the lack of relevant studies. Furthermore, no studies have reported secondary outcomes such as length of stay or adverse events related to SSI. The optimal dosing interval also remains unknown. The guidelines of the American Society of Health‐System Pharmacists (ASHSP) 9 recommend that intraoperative redosing is necessary if the duration of the procedure exceeds two half‐lives of the drug or if there is excessive blood loss during the procedure. Although the benefit of this approach seems reasonable from a drug pharmacokinetic perspective, the guidelines have not addressed the duration of surgical procedures or redosing in relation to SSI in antibiotic prophylaxis protocols. Thus, no recommendations were made regarding the benefits or disadvantages of this approach in our study.

This study has several limitations. First, owing to the lack of data from RCTs, our conclusions were solely derived from the evidence provided by observational studies. Second, several studies did not report variables related to surgical interventions that are susceptible to SSI occurrence, such as the type of surgery, CDC wound class, types of prophylactic antibiotics used, and the timing of initial antibiotic administration. Third, the exact amount of antibiotics needed for intraoperative redosing remains unknown and may vary based on factors such as body weight, obesity, the type of antibiotic, and the extent of blood loss. Fourth, the definition of SSI incidence varied across the studies. Moreover, certain coexisting conditions, such as diabetes mellitus or renal dysfunction, obesity, smoking status, length of previous hospital stay, and violation of asepsis during surgery, are among the predictors of SSI that might confound our results, should they be related to the probability of an intraoperative antibiotic redoses. As the most plausible effect of a high‐risk profile is to increase the likelihood of intraoperative redosing, adjustment for this profile would lead to an increase in the apparent benefit. However, the limitations of our study should be acknowledged when evaluating the practical application of the results. Fifth, funnel plot asymmetry was detected in our analysis, indicating that negative results (i.e., odds ratio < 1) were found in most studies with smaller sample sizes. Therefore, the possibility of publication bias cannot be ignored, given the likelihood that studies demonstrating the effect of the intraoperative redosing protocol on the primary outcome (e.g., incidence of SSI) are preferentially selected and published. To address these issues, future research efforts should involve large‐scale RCTs to address these limitations and enable high‐quality meta‐analyses. However, conducting such trials may be unethical given the present findings. Therefore, our findings are significant as they represent the best available evidence regarding the clinical benefit of intraoperative redosing in patients undergoing prolonged surgery.

5. CONCLUSIONS

In this systematic review and meta‐analysis of seven observational studies involving 4,671 patients, intraoperative redosing of prophylactic antibiotics during lengthy surgeries was associated with a significantly lower risk of SSI than non‐redosing. Therefore, for surgeries lasting longer than approximately 3–4 h, we recommend intraoperative redosing to reduce the risk of infection. Further research is needed to clarify the optimal redosing interval, which should be prioritized in future studies.

AUTHOR CONTRIBUTIONS

Yuki Hanai: Conceptualization; data curation; formal analysis; investigation; methodology; project administration; writing – original draft; writing – review and editing. Jun Hirai: Conceptualization; methodology; project administration; supervision; writing – original draft; writing – review and editing. Masahiro Kobayashi: Conceptualization; methodology; project administration; supervision; writing – original draft; writing – review and editing. Kazuhiro Matsuo: Data curation; formal analysis; investigation; methodology. Keita Kouzu: Methodology; writing – review and editing. Hiroji Shinkawa: Methodology; writing – review and editing. Seiichi Shinji: Methodology; writing – review and editing. Motomu Kobayashi: Methodology; writing – review and editing. Yuichi Kitagawa: Methodology; writing – review and editing. Chizuru Yamashita: Methodology; writing – review and editing. Yasuhiko Mohri: Methodology; writing – review and editing. Hiroshi Nobuhara: Methodology; writing – review and editing. Katsunori Suzuki: Methodology; writing – review and editing. Junzo Shimizu: Methodology; writing – review and editing. Motoi Uchino: Methodology; writing – review and editing. Seiji Haji: Methodology; writing – review and editing. Masahiro Yoshida: Methodology; supervision; writing – review and editing. Toru Mizuguchi: Methodology; supervision; writing – review and editing. Toshihiko Mayumi: Methodology; supervision; writing – review and editing. Yuko Kitagawa: Methodology; supervision; writing – review and editing. Hiroki Ohge: Conceptualization; methodology; project administration; supervision; writing – original draft; writing – review and editing.

FUNDING INFORMATION

This study did not receive any specific grants from funding agencies in the public, commercial, or non‐profit sectors.

CONFLICT OF INTEREST STATEMENT

Hiroki Ohge is an editorial member of Annals of Gastroenterological Surgery. Yuko Kitagawa is an Editor‐in‐Chief of Annals of Gastroenterological Surgery. The remaining authors declare no conflicts of interest for this article.

ETHICS STATEMENT

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

Supporting information

Figures S1–S2.

AGS3-9-369-s001.pdf (126.2KB, pdf)

Table S1.

AGS3-9-369-s002.docx (12.6KB, docx)

ACKNOWLEDGEMENTS

We would like to thank Editage (www.editage.jp) for the English language editing.

Hanai Y, Hirai J, Kobayashi M, Matsuo K, Kouzu K, Shinkawa H, et al. Intraoperative redosing of antibiotics for prevention of surgical site infections: A systematic review and meta‐analysis. Ann Gastroenterol Surg. 2025;9:369–378. 10.1002/ags3.12866

DATA AVAILABILITY STATEMENT

All data generated or analyzed in this study are included in the published article.

REFERENCES

  • 1. Young PY, Khadaroo RG. Surgical site infections. Surg Clin North Am. 2014;94:1245–1264. [DOI] [PubMed] [Google Scholar]
  • 2. Berríos‐Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for Disease Control and Prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152:784–791. [DOI] [PubMed] [Google Scholar]
  • 3. Ohge H, Takesue Y, Yokoyama T, Murakami Y, Hiyama E, Yokoyama Y, et al. An additional dose of cefazolin for intraoperative prophylaxis. Surg Today. 1999;29:1233–1236. [DOI] [PubMed] [Google Scholar]
  • 4. James M, Martinez EA. Antibiotics and perioperative infections. Best Pract Res Clin Anaesthesiol. 2008;22:571–584. [DOI] [PubMed] [Google Scholar]
  • 5. Cheng H, Chen BP, Soleas IM, Ferko NC, Cameron CG, Hinoul P. Prolonged operative duration increases risk of surgical site infections: a systematic review. Surg Infect. 2017;18:722–735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Scher KS. Studies on the duration of antibiotic administration for surgical prophylaxis. Am Surg. 1997;63:59–62. [PubMed] [Google Scholar]
  • 7. Zanetti G, Giardina R, Platt R. Intraoperative redosing of cefazolin and risk for surgical site infection in cardiac surgery. Emerg Infect Dis. 2001;7:828–831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, et al. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the trial to reduce antimicrobial prophylaxis errors. Ann Surg. 2009;250:10–16. [DOI] [PubMed] [Google Scholar]
  • 9. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70:195–283. [DOI] [PubMed] [Google Scholar]
  • 10. Japanese Society of Chemotherapy and Japan Society for Surgical Infection . Japanese Clinical Practice Guidelines for antimicrobial prophylaxis in surgery 2016 [in Japanese]. [cited 2023 Dec 5] Available from: http://www.gekakansen.jp/file/antimicrobial‐guideline.pdf
  • 11. World Health Organizations . Global guidelines for the prevention of surgical site infection. 2nd ed. 2018. [cited 2023 Dec 10] Available from: https://www.who.int/publications/i/item/9789241550475 [PubMed]
  • 12. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) hospital infection control practices advisory committee. Am J Infect Control. 1999;27:97–132. quiz 133–4; discussion 96. [PubMed] [Google Scholar]
  • 14. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane handbook for systematic reviews of interventions. Cochrane Database Syst Rev. 2019;10:ED000142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS‐I: a tool for assessing risk of bias in non‐randomised studies of interventions. BMJ. 2016;355:i4919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Morita S, Nishisho I, Nomura T, Fukushima Y, Morimoto T, Hiraoka N, et al. The significance of the intraoperative repeated dosing of antimicrobials for preventing surgical wound infection in colorectal surgery. Surg Today. 2005;35:732–738. [DOI] [PubMed] [Google Scholar]
  • 17. Zhang Y, Mahar AL, Edgar B, Williams V, Wallace D, Vearncombe M, et al. Length of surgery and intra‐operative best practices determine surgical site infection risk in operations of prolonged duration. Can J Infect Control. 2015;30:158–164. [Google Scholar]
  • 18. Bertschi D, Weber WP, Zeindler J, Stekhoven D, Mechera R, Salm L, et al. Antimicrobial prophylaxis Redosing reduces surgical site infection risk in prolonged duration surgery irrespective of its timing. World J Surg. 2019;43:2420–2425. [DOI] [PubMed] [Google Scholar]
  • 19. de Jonge SW, Boldingh QJJ, Koch AH, Daniels L, De Vries EN, Spijkerman IJ, et al. Timing of preoperative antibiotic prophylaxis and surgical site infection: TAPAS, an observational cohort study. Ann Surg. 2021;274:e308–e314. [DOI] [PubMed] [Google Scholar]
  • 20. Wolfhagen N, Boldingh QJJ, de Lange M, Boermeester MA, de Jonge SW. 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. Ann Surg. 2022;275:1050–1057. [DOI] [PubMed] [Google Scholar]
  • 21. Calderwood MS, Anderson DJ, Bratzler DW, Dellinger EP, Garcia‐Houchins S, Maragakis LL, et al. Strategies to prevent surgical site infections in acute‐care hospitals: 2022 update. Infect Control Hosp Epidemiol. 2023;44:695–720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Zelenitsky SA, Calic D, Arora RC, Grocott HP, Lakowski TM, Lillico R, et al. Antimicrobial prophylaxis for patients undergoing cardiac surgery: intraoperative cefazolin concentrations and sternal wound infections. Antimicrob Agents Chemother. 2018;62:e01360‐18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Zelenitsky SA, Ariano RE, Harding GK, Silverman RE. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother. 2002;46:3026–3030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Colombo MZG, Negri L, Scalambrino S, Scalambrino S, Pasta F, Arreghini A. A randomized comparison of one‐dose versus two‐dose antibiotic prophylaxis in gynaecologic surgery lasting over two hours. Italian J Gynaecol Obstet. 1998;10:9–15. [Google Scholar]
  • 25. Cuthbertson AM, McLeish AR, Penfold JC, Ross H. A comparison between single and double dose intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery. Dis Colon Rectum. 1991;34:151–155. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Figures S1–S2.

AGS3-9-369-s001.pdf (126.2KB, pdf)

Table S1.

AGS3-9-369-s002.docx (12.6KB, docx)

Data Availability Statement

All data generated or analyzed in this study are included in the published article.


Articles from Annals of Gastroenterological Surgery are provided here courtesy of Wiley

RESOURCES