Abstract
Background
Recent guidelines about preventing surgical site infections (SSIs) recommend against the administration of prophylactic antibiotics after surgery. However, many colorectal surgeons still prefer prolonged use of prophylactic antibiotics. While minimally invasive surgery (MIS) has become the standard for colorectal cancer surgery, there were few studies about proper dose of prophylactic antibiotics in minimally invasive colorectal surgery.
Methods
This is a retrospective study. All patients underwent elective colorectal cancer surgery using MIS. Intravenous cefotetan was administered as a prophylactic antibiotic. Two groups were classified according to the dose of prophylactic antibiotics: a group using a single dose preoperatively (single-dose group) and a group using a preoperative single dose plus additional doses within 24 hours after surgery (multiple-dose group). The SSI rates between the two groups were compared before and after propensity score matching (PSM). Risk factors of SSIs were assessed using univariate and multivariable analysis.
Results
There were 902 patients in the single-dose group and 330 patients in the multiple-dose group. After PSM, 320 patients were included in each group. There were no differences in baseline characteristics and surgical outcomes except the length of hospital stay. SSI rates were not different between the two groups before and after PSM (before 2.0% vs. 2.1%, P = 0.890; after 0.9% vs. 1.9%, P = 0.505). In multivariable analysis, American Society of Anesthesiologists class 3, rectal surgery, intraoperative transfusion, and larger tumor size were identified as independent factors associated with SSI incidence.
Conclusion
A single preoperative dose of prophylactic antibiotics may be sufficient to prevent SSIs in elective MIS for colorectal cancer.
Keywords: Minimally Invasive Colorectal Surgery, Prophylactic Antibiotics, Cefotetan, Single Preoperative Dose, Single Preoperative Dose + Multiple Postoperative Doses, Surgical Site Infection (SSI)
Graphical Abstract
INTRODUCTION
Colorectal surgery includes procedures of the resection and anastomosis of the large intestine and involves exposure to a higher risk of surgical site infection (SSI) than other general surgeries. The SSI rates for elective colorectal surgery had been about 10–30%.1,2,3,4 Therefore, many colorectal surgeons routinely administer prophylactic intravenous (IV) antibiotics for several days to prevent SSIs. However, in recent studies, the long-term use of IV antibiotics for over 24 hours after surgery increased the risk of Clostridium difficile infection and other complications such as acute kidney injury.5,6 Moreover, the unnecessary use of antibiotics can contribute to antimicrobial resistance. Researchers have suggested that prophylactic antibiotics should be discontinued within 24 hours of surgery termination.7
The latest guidelines for SSI prevention were published in 2017 by the Centers for Disease Control and Prevention (CDC) and in 2018 by the World Health Organization (WHO). According to these guidelines, prophylactic antibiotics should be administered as a single dose before surgery and no additional doses are needed after the surgery.8,9 It has been proposed that the prolonged use of antibiotics after the closure of surgical incisions may not be helpful in reducing SSIs in clean-contaminated general surgery. The guidelines state that the postoperative use of antibiotics is beneficial only in a few surgeries, such as cardiac or vascular surgeries.
Minimally invasive surgery (MIS) has become a standard procedure for colorectal surgery, and has been reported to have a lower rate of SSIs than open surgery.10,11,12,13,14,15 Nevertheless, many colorectal surgeons still prefer the prolonged use of prophylactic antibiotics based on their personal experience with SSIs.16 In an international survey conducted in 2020, 55.9% of surgeons routinely administered postoperative antibiotics after laparoscopic right hemicolectomy.17 There is a gap between these guidelines and the actual world; therefore, further research on colorectal MIS is required to address this discrepancy.
Few studies have investigated the optimal dose of prophylactic antibiotics for minimally invasive colorectal surgery. Therefore, in this study, we aimed to clarify the proper dose of prophylactic antibiotics by comparing the SSI rates between the group using prophylactic antibiotics as a single dose before surgery and the group using multiple doses within 24 hours after surgery in MIS for colorectal cancer.
METHODS
This is a retrospective study using prospectively collected data of patients who underwent colorectal surgery between January 2015 and December 2020 at a tertiary hospital in South Korea. Patients were diagnosed with biopsy-proven colorectal cancer and underwent preoperative evaluation using laboratory, radiological, and endoscopic tests. Curative-intent operations and an American Society of Anesthesiologists (ASA) classification of < 4 were included. All procedures were performed using MIS, such as laparoscopy-assisted or robotic-assisted surgery. IV cefotetan was administered as a prophylactic antibiotic. Exclusion criteria were open or open converted surgery, palliative or emergent surgery, distant metastasis or other synchronous malignancies, combined resection of major organs, and administration of IV antibiotics preoperatively for other infectious diseases. Medical records were reviewed for information on patient characteristics and surgical and pathological outcomes.
In this study, cefotetan was administered as a parenteral prophylactic antibiotic during colorectal surgery. Cefotetan is a second-generation cephalosporin, classified as cephamycin, that acts on both aerobes and anaerobes including Bacteroides fragilis. A single 2 g dose of cefotetan was administered intravenously for antibiotic prophylaxis within 60 minutes before the incision was made. The total dose of prophylactic antibiotics was changed according to the institutional policy. The drug was administered in multiple doses (one or two more additional doses after surgery) within 24 hours of termination of the surgery until 2018. After 2019, a single preoperative dose was introduced according to the WHO guidelines. In this study, two groups were classified according to the dose of prophylactic antibiotics: a group using a single dose preoperatively (single-dose group) and a group using a preoperative single dose plus additional doses within 24 hours after surgery (multiple-dose group).
All patients were administered oral antibiotics (OA) before surgery. Rifaximin, used as OA, is a broad-spectrum antibiotic that targets both aerobic and anaerobic bacteria including C. difficile. The patients received Rifaximin 200 mg 2T bid the day before surgery. Additionally, all patients were hospitalized 2 days before surgery, and mechanical bowel preparation (MBP) was performed if they had no symptoms of bowel perforation or obstruction. The agents for MBP were Picosolution® (a combination of citric acid hydrate, magnesium oxide, and sodium picosulfate) or 2 L of Colyte® (polyethylene glycol).
In the operating room, the surgical site was sterilized using an alcohol-based chlorhexidine gluconate solution, and a disposable drape was used. The operators applied the antimicrobial soap appropriately to their forearms and wore sterile clothes and gloves. During the operation, a wound protector device was used for the mini-laparotomy. If needed during rectal surgery, a stoma was created on one side of the lower abdomen. Intraabdominal Jackson-Pratt (JP) drains were inserted into the operative field through one of the trocar sites. Abdominal fascia closure was conducted continuously with PDS II® (polydioxanone) or intermittently with Vicryl® (polyglactin). The skin was closed using sutures, staplers, or surgical glue.
Postoperatively, the wound was dressed every 2 to 3 days using povidone iodine solution along with either gauze or foam materials. If the wound was sealed with surgical glue, only an inspection was performed. All stitches and JP drains were typically removed within a week after surgery, unless wound problems arose requiring their retention.
SSIs were defined according to the criteria of the CDC National Healthcare Safety Network and classified as superficial incisional SSI, deep incisional SSI, or organ/space SSI. The surgeons assessed the wounds daily after surgery and classified SSIs, if occurred. Generally, incisional SSIs were diagnosed with patients’ symptoms or signs of wounds. Organ/space SSIs were detected by drain color change and/or confirmed with radiologic image. SSIs that occurred after discharge were confirmed in the outpatient clinic until postoperative day 30.
Both groups were compared using the χ2 test or Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. To identify the risk factors for SSIs, multivariate analysis was conducted using a logistic regression analysis model with significantly different variables following univariate analysis.
To control confounding factors from different general characteristics between the two groups, propensity score matching (PSM) was performed to match the two groups 1:1 for the following factors: sex, age, body mass index, ASA classification, diabetes mellitus, current smoking, alcohol intake, preoperative symptoms, neoadjuvant treatment, tumor location, tumor-related complications, carcinoembryonic antigen (CEA) level, operators, stoma formation, operation time, and estimated blood loss.
All statistical tests were two-sided. P values of less than 0.05 were considered significant. All statistical analyses were conducted using IBM SPSS Statistics version 26 (IBM Corporation, Armonk, NY, USA).
Ethics statement
This study was approved by the Institutional Review Board of Seoul National University Hospital (No. 2305-154-1435). Informed consent was not required because of the retrospective nature of the study.
RESULTS
In total, 2,676 patients met the inclusion criteria and underwent laparoscopic or robotic surgery for colorectal cancer at Seoul National University Hospital from 2015 to 2020 (Fig. 1). Based on the exclusion criteria, 556 patients were excluded. An additional 863 patients were excluded because they had been administered prophylactic antibiotics other than cefotetan. In 23 patients, antibiotics were continued for > 24 hours postoperatively. Excluding 2 missing data, 1,232 patients were finally analyzed, with 902 patients in the single-dose group and 330 patients in the multiple-dose group. After PSM, 320 patients were included in each group.
Fig. 1. Patient selection.
SNUH = Seoul National University Hospital, IV = intravenous, PSM = propensity score matching.
The baseline characteristics of both groups are shown in Table 1. Before PSM, more patients in the single-dose group than those in the multiple-dose group had a history of alcohol intake (35.9% vs. 28.8%, P = 0.019). The number of symptomatic patients was higher in the single-dose group than in the multiple-dose group (45.5% vs. 37.6%, P = 0.046). Preoperative CEA level was higher in the multiple-dose group than the single-dose group (≥ 5 ng/mL, 15.6% vs. 20.9%, P = 0.029). After PSM, no significant differences were observed between the two groups.
Table 1. Baseline characteristics before and after PSM.
| Variables | Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|---|
| Single-dose (n = 902) | Multiple-dose (n = 330) | P value | Single-dose (n = 320) | Multiple-dose (n = 320) | P value | ||
| Age, yr | 64 (56–73) | 65 (56–72) | 0.756 | 64 (56–73) | 65 (56–72) | 0.846 | |
| Sex | 0.924 | 0.872 | |||||
| Male | 533 (59.1) | 194 (58.8) | 189 (59.1) | 187 (58.4) | |||
| Female | 369 (40.9) | 136 (41.2) | 131 (40.9) | 133 (41.6) | |||
| BMI, kg/m2 | 24.1 (21.7–26.2) | 23.8 (21.7–25.8) | 0.218 | 23.6 (21.7–25.9) | 23.8 (21.7–25.8) | 0.845 | |
| Medical history | |||||||
| DM | 206 (22.8) | 74 (22.4) | 0.878 | 75 (23.4) | 71 (22.2) | 0.706 | |
| HTN | 389 (43.1) | 139 (42.1) | 0.752 | 140 (43.8) | 134 (41.9) | 0.632 | |
| Heart disease | 83 (9.2) | 28 (8.5) | 0.697 | 30 (9.4) | 28 (8.8) | 0.783 | |
| Pulmonary disease | 89 (9.9) | 32 (9.7) | 0.929 | 35 (10.9) | 31 (9.7) | 0.603 | |
| Liver disease | 56 (6.2) | 23 (7.0) | 0.629 | 22 (6.9) | 23 (7.2) | 0.877 | |
| ASA classification | 0.658 | 0.587 | |||||
| 1 | 228 (25.3) | 78 (23.6) | 68 (21.3) | 77 (24.1) | |||
| 2 | 612 (67.8) | 225 (68.2) | 229 (71.6) | 217 (67.8) | |||
| 3 | 62 (6.9) | 27 (8.2) | 23 (7.2) | 26 (8.1) | |||
| Social history | |||||||
| Smoking | 143 (15.9) | 48 (14.5) | 0.574 | 47 (14.7) | 46 (14.4) | 0.911 | |
| Alcohol intake | 324 (35.9) | 95 (28.8) | 0.019* | 96 (30.0) | 94 (29.4) | 0.863 | |
| Other cancer history | 63 (7.0) | 33 (10.0) | 0.080 | 19 (5.9) | 32 (10.0) | 0.058 | |
| Preop symptoms | 0.046* | 0.817 | |||||
| None | 492 (54.5) | 206 (62.4) | 205 (64.1) | 197 (61.6) | |||
| GI bleeding | 205 (22.7) | 55 (16.7) | 55 (17.2) | 54 (16.9) | |||
| Abdominal pain | 105 (11.6) | 31 (9.4) | 25 (7.8) | 31 (9.7) | |||
| Bowel habit change | 100 (11.1) | 38 (11.5) | 35 (10.9) | 38 (11.9) | |||
| Number of tumors | 0.856 | 0.832 | |||||
| Single | 870 (96.5) | 319 (96.7) | 308 (96.3) | 309 (96.6) | |||
| Multiple | 32 (3.5) | 11 (3.3) | 12 (3.8) | 11 (3.4) | |||
| Tumor location | 0.195 | 0.722 | |||||
| Rt-sided | 211 (23.4) | 89 (27.0) | 89 (27.8) | 85 (26.6) | |||
| Lt-sided | 691 (76.6) | 241 (73.0) | 231 (72.2) | 235 (73.4) | |||
| Preop complications | |||||||
| Perforation | 13 (1.4) | 2 (0.6) | 0.379 | 6 (1.9) | 2 (0.6) | 0.155 | |
| Obstruction | 102 (11.3) | 42 (12.7) | 0.492 | 37 (11.6) | 40 (12.5) | 0.715 | |
| Preop CEA, ng/mL | 0.029* | 0.078 | |||||
| < 5 | 761 (84.4) | 261 (79.1) | 272 (85.0) | 255 (79.7) | |||
| ≥ 5 | 141 (15.6) | 69 (20.9) | 48 (15.0) | 65 (20.3) | |||
| Neoadjuvant treatment | 0.747 | 0.292 | |||||
| Not done | 804 (89.1) | 292 (88.5) | 292 (91.3) | 284 (88.8) | |||
| Done | 98 (10.9) | 38 (11.5) | 28 (8.8) | 36 (11.3) | |||
Values are presented as median (interquartile range) or number (%).
PSM = propensity score matching, BMI = body mass index, DM = diabetes mellitus, HTN = hypertension, ASA = American Society of Anesthesiologists, GI = gastrointestinal, Rt = right, Lt = left, CEA = carcinoembryonic antigen.
*P < 0.05.
Table 2 shows the operative and pathological outcomes. Before PSM, more senior surgeons were included in the multiple-dose group than in the single-dose group (82.3% vs. 88.2%, P = 0.012). Estimated blood loss was higher in the multiple-dose group than in the single-dose group (50 [interquartile range; IQR, 30–100] vs. 100 [IQR, 50–200] mL, P < 0.001). Intraoperative transfusions were more frequent in the multiple-dose group than in the single-dose group, although the difference was not significant (1.0% vs. 2.4%; P = 0.057). Postoperative complications were not different; however, the length of hospital stay was longer in the single-dose group than the multiple-dose group (6 [IQR, 5–7] vs. 5 [IQR, 5–6] days, P < 0.001). Tumor size was larger in the multiple-dose group than in the single-dose group (3.2 [IQR, 2.0–5.0] vs. 3.5 [IQR, 2.1–5.5] cm, P = 0.006). After PSM, the length of hospital stay was still longer in the single-dose group than in the multiple-dose group; however, the other outcomes did not differ between the two groups.
Table 2. Operative and pathologic outcomes before and after PSM.
| Variables | Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|---|
| Single-dose (n = 902) | Multiple-dose (n = 330) | P value | Single-dose (n = 320) | Multiple-dose (n = 320) | P value | ||
| Operation type | 0.421 | 0.541 | |||||
| RHC/TC | 207 (22.9) | 86 (26.1) | 86 (26.9) | 82 (25.6) | |||
| LHC/AR | 360 (39.9) | 118 (35.8) | 129 (40.3) | 116 (36.3) | |||
| LAR/ISR/APR | 320 (35.5) | 118 (35.8) | 97 (30.3) | 114 (35.6) | |||
| Hartman operation/others | 15 (1.7) | 8 (2.4) | 8 (2.5) | 8 (2.5) | |||
| Operator | 0.012* | 0.709 | |||||
| Senior | 742 (82.3) | 291 (88.2) | 285 (89.1) | 282 (88.1) | |||
| Junior | 160 (17.7) | 39 (11.8) | 35 (10.9) | 38 (11.9) | |||
| Approach type | 0.205 | > 0.999 | |||||
| Laparoscopic | 877 (97.2) | 325 (98.5) | 315 (98.4) | 316 (98.8) | |||
| Robotic | 25 (2.8) | 5 (1.5) | 5 (1.6) | 4 (1.3) | |||
| Ostomy formation | 160 (17.7) | 51 (15.5) | 0.346 | 40 (12.5) | 49 (15.3) | 0.304 | |
| Operation time, min | 147 (120–180) | 145 (115–190) | 0.811 | 144 (120–184) | 144 (115–190) | 0.913 | |
| Estimated blood loss, mL | 50 (30–100) | 100 (50–200) | < 0.001* | 100 (50–150) | 100 (50–150) | 0.240 | |
| Intraoperative transfusion | 9 (1.0) | 8 (2.4) | 0.057 | 2 (0.6) | 4 (1.3) | 0.686 | |
| Length of hospital stay, days | 6 (5–7) | 5 (5–6) | < 0.001* | 6 (5–7) | 5 (5–6) | < 0.001* | |
| Postop complications | 214 (23.7) | 80 (24.2) | 0.850 | 66 (20.6) | 76 (23.8) | 0.341 | |
| CDC grade ≥ 3 | 15 (1.7) | 8 (2.4) | 0.382 | 3 (0.9) | 6 (1.9) | 0.505 | |
| Re-operation | 6 (0.7) | 2 (0.6) | > 0.999 | 1 (0.3) | 1 (0.3) | > 0.999 | |
| Mortality | 1 (0.1) | 1 (0.3) | 0.464 | 1 (0.3) | 1 (0.3) | > 0.999 | |
| Histology | 0.491 | 0.122 | |||||
| Well-differentiated | 173 (19.2) | 68 (20.6) | 60 (18.8) | 66 (20.6) | |||
| Moderately-differentiated | 656 (72.7) | 231 (70.0) | 234 (73.1) | 224 (70.0) | |||
| Poorly-differentiated | 31 (3.4) | 17 (5.2) | 7 (2.2) | 17 (5.3) | |||
| Others | 42 (4.7) | 14 (4.2) | 19 (5.9) | 13 (4.1) | |||
| Tumor size, cm | 3.2 (2.0–5.0) | 3.5 (2.1–5.5) | 0.006* | 3.4 (1.7–5.0) | 3.5 (2.1–5.5) | 0.059 | |
| Number of harvested LNs | 0.359 | 0.440 | |||||
| < 12 | 47 (5.2) | 13 (3.9) | 16 (5.0) | 12 (3.8) | |||
| ≥ 12 | 855 (94.8) | 317 (96.1) | 304 (95.0) | 308 (96.3) | |||
| AJCC stage | 0.513 | 0.621 | |||||
| 0 | 23 (2.5) | 8 (2.4) | 10 (3.1) | 8 (2.5) | |||
| 1 | 284 (31.5) | 106 (32.1) | 96 (30.0) | 102 (31.9) | |||
| 2 | 254 (28.2) | 105 (31.8) | 92 (28.7) | 102 (31.9) | |||
| 3 | 341 (37.8) | 111 (33.6) | 122 (38.1) | 108 (33.8) | |||
Values are presented as median (interquartile range) or number (%).
PSM = propensity score matching, RHC = right hemicolectomy, TC = transverse colectomy, LHC = left hemicolectomy, AR = anterior resection, LAR = low anterior resection, ISR = intersphincteric resection, APR = abdominoperineal resection, CDC = Clavien-Dindo classification, LN = lymph node, AJCC = American Joint Committee on Cancer.
*P < 0.05.
The overall incidence of SSIs was not significantly different between the single-dose and multiple-dose groups before and after PSM (before PSM: 2.0% vs. 2.1%, P = 0.890; after PSM: 0.9% vs. 1.9%, P = 0.505; Table 3). When compared according to each SSI class, no differences were observed between the two groups before and after PSM. Further details and management of SSI cases are summarized in Supplementary Table 1 and all other types of postoperative complications were presented in Supplementary Table 2.
Table 3. The rate of surgical site infection before and after PSM.
| Variables | Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|---|
| Single-dose (n = 902) | Multiple-dose (n = 330) | P value | Single-dose (n = 320) | Multiple-dose (n = 320) | P value | ||
| Surgical site infection | 18 (2.0) | 7 (2.1) | 0.890 | 3 (0.9) | 6 (1.9) | 0.505 | |
| Superficial SSI | 5 (0.6) | 3 (0.9) | 0 | 3 (0.9) | |||
| Deep SSI | 2 (0.2) | 0 | 1 (0.3) | 0 | |||
| Deep organ infection | 11 (1.2) | 4 (1.2) | 2 (0.6) | 3 (0.9) | |||
| Other wound problems | 8 (0.9) | 6 (1.8) | 0.172 | 6 (1.9) | 6 (1.9) | > 0.999 | |
| Wound seroma | 7 (0.8) | 3 (0.9) | 6 (1.9) | 3 (0.9) | |||
| Wound dehiscence | 1 (0.1) | 3 (0.9) | 0 | 3 (0.9) | |||
Values are presented as number (%).
PSM = propensity score matching, SSI = surgical site infection.
In the univariate analysis, the SSI rate was significantly different among the ASA classification groups, types of operation, operation time, intraoperative transfusion, and tumor size (Supplementary Table 3). In multivariate analysis incorporating these variables, ASA class 3, rectal surgery-low anterior resection (LAR), intersphincteric resection (ISR), and abdominoperineal resection (APR)-, intraoperative transfusion, and larger tumor size were identified as independent factors associated with SSI incidence (Table 4). Notably, the dose of prophylactic antibiotics did not exhibit a significant correlation with SSIs, even after adjusting for confounding factors.
Table 4. Multivariate analysis for risk factors of surgical site infection.
| Variables | OR | 95% CI | P value | |
|---|---|---|---|---|
| ASA classification | 0.023* | |||
| 1 | Ref. | |||
| 2 | 3.835 | 0.866–16.979 | 0.077 | |
| 3 | 10.417 | 1.887–57.505 | 0.007* | |
| Operation type | 0.042* | |||
| LHC/AR | Ref. | |||
| RHC/TC | 8.257 | 0.977–69.760 | 0.053 | |
| LAR/ISR/APR | 16.702 | 2.136–130.580 | 0.007* | |
| Hartman operation/others | 10.102 | 0.560–182.361 | 0.117 | |
| Operation time, min | ||||
| ≤ 145 | Ref. | |||
| > 145 | 2.009 | 0.754–5.348 | 0.163 | |
| Intraoperative transfusion | ||||
| No | Ref. | |||
| Yes | 7.595 | 1.462–39.456 | 0.016* | |
| Tumor size, cm | ||||
| ≤ 3.4 | Ref. | |||
| > 3.4 | 4.512 | 1.702–11.962 | 0.002* | |
| Prophylactic antibiotics | ||||
| Single-dose | Ref. | |||
| Multiple-dose | 0.856 | 0.342–2.141 | 0.740 | |
OR = odds ratio, CI = confidence interval, ASA = American Society of Anesthesiologists, LHC = left hemicolectomy, AR = anterior resection, RHC = right hemicolectomy, TC = transverse colectomy, LAR = low anterior resection, ISR = intersphincteric resection, APR = abdominoperineal resection.
*P < 0.05.
DISCUSSION
This study aimed to assess the overall incidence of SSIs in minimally invasive colorectal surgery by comparing two groups using prophylactic antibiotics as a single dose preoperatively and multiple doses within 24 hours after surgery. PSM was conducted to adjust for potential confounding factors that differed in baseline characteristics. SSI rates before and after PSM were not significantly different between the two groups.
The SSI rate observed in this study was approximately 2%, which was slightly lower than that reported previously. This can be attributed to the study's focus on laparoscopic surgeries while excluding open surgeries, along with strict adherence to the established SSI prevention guidelines within our institution. Laparoscopic surgery typically has lower SSI rates than open surgery. In previous studies, the SSI rate ranged from 15–30% for open colorectal surgeries, and 2–10% for laparoscopic colorectal surgeries.1,2,3,4,18,19,20,21,22 Moreover, recent studies have shown a trend toward decreasing SSI rates over time. For example, one study noted that the SSI rate in colon surgeries was 3.56% in 2019, in contrast to 13.33% in 2010.23
In 2007, Fujita et al.24 argued in a randomized controlled trial that the administration of triple-dose prophylactic antibiotics led to a lower incidence of SSIs in elective colon surgery than single-dose antibiotics. However, their study used cefmetazole as a prophylactic antibiotic, which has a shorter half-life of 1.5 hours compared to cefotetan with half-life of 3–4 hours.25,26 According to the WHO guidelines, additional antibiotic doses are recommended when the duration of surgery exceeds twice the half-life of prophylactic antibiotics. In Fujita’s study, the mean duration of surgery was approximately 3 hours, with over 30% lasting longer than 3 hours. Therefore, a single dose of cefmetazole with a short half-life may be insufficient to cover the entire duration of surgery. Furthermore, this study included both open and laparoscopic surgeries. In a subgroup analysis focusing on laparoscopic surgeries and excluding open surgeries, there was no difference in SSI rates between the single- and triple-dose groups.27
In contrast, Suzuki et al.28 suggested that a single dose of IV antibiotics immediately before surgery was sufficient to prevent perioperative infection in elective colon cancer surgery. In this randomized clinical trial, infection rates were compared between a group using a single dose of flomoxef before surgery and a group using the agent twice daily for 4 days. There were no significant differences in the incidence of incisional SSIs and organ/space SSIs between the two groups. These findings were consistent with ours but differed from our study in that open surgery, not MIS, was targeted.
Current guidelines recommend administering prophylactic antibiotics parenterally for colorectal surgery as follows: cefazoline with metronidazole, cefoxitin, cefotetan, ampicillin-sulbactam, ceftriaxone with metronidazole and ertapenem.7,29,30 For elective colon surgery, antimicrobial prophylaxis should include Gram-positive and Gram-negative aerobes and anaerobes. The half-life of the drug and average operative time should also be considered in the selection of antibiotics. In our institution, cefotetan has been the primary prophylactic antibiotic used for colorectal surgery. For a certain period, moxifloxacin was used as an alternative because it does not require a skin test and has a long half-life of 12 hours. Moxifloxacin is still administered to patients who react positive on a skin test. In this study, we focused on cefotetan, as it is the most commonly used first-line prophylactic antibiotic for colorectal surgery. Therefore, 863 patients, the majority of whom received moxifloxacin, were excluded from the analysis. This exclusion could potentially lead to selection bias.
Recommendations regarding the duration and dose of prophylactic surgical antibiotics have changed over time. In 2013, the American Society of Health-System Pharmacists and Infectious Diseases Society of America recommended discontinuation of prophylactic antibiotics within 24 hours after surgery.7 The 2014 guidelines of the Society for Healthcare Epidemiology of America also allow the use of surgical prophylactic antibiotics within 24 hours postoperatively.31 However, a publication by the Cochrane Library in 2015 on antimicrobial prophylaxis for colorectal surgery concluded that there was no evidence to support the use of more than a single preoperative dose, and that it actually encouraged the occurrence of resistant bacteria and C. difficile.32 In 2017, the CDC guidelines suggested not administering additional prophylactic antimicrobial agents after the surgical incision is closed in the operating room during clean and clean-contaminated procedures.9 The latest WHO guidelines for preventing SSIs recommend against the administration of prophylactic antibiotics after completion of general surgery.8 While most guidelines are based on researches including general surgery or clean-contaminated surgery, there are currently not many studies targeting only minimally invasive colorectal surgeries.
Previously revealed risk factors for SSIs include patient-related factors such as male sex, diabetes mellitus, smoking, obesity, steroid use, and radiation history and operation-related factors such as longer operation time, large blood loss, intraoperative transfusion, stoma formation, and emergent operation.33,34,35,36,37,38,39 Our analysis investigated various factors influencing SSIs and identified a higher ASA class, rectal surgery (LAR, ISR, APR), intraoperative transfusion, and larger tumor size as risk factors for SSIs. Patients with these risk factors may require meticulous postoperative management to prevent SSIs even if they undergo MIS.
The length of hospital stay differed between the two groups, even after PSM. After the laparoscopic procedure became the standard at our institution, patients were usually discharged within 7 days after surgery. Owing to the characteristics of the Korean medical system, there is a tendency to continue hospitalization even if there are no special medical problems. Depending on the individual surgeon or patient’s preference, there may be a variation in hospital stay of one or two days. Therefore, we believe that this difference was independent of the surgical procedure.
There are some limitations. This study was retrospective and conducted at a single center. Nevertheless, this study has the advantage of having a relatively large number of patients and that only antibiotic doses were categorized differently at a single institution with constant other conditions, which makes this result valuable as baseline data for future studies.
In conclusion, there were no significant differences in SSI rates between the group using prophylactic antibiotics as a single dose preoperatively and the group using multiple doses within 24 hours after surgery in minimally invasive colorectal surgery. Therefore, a single preoperative dose of prophylactic antibiotics may be sufficient to prevent SSIs during elective MIS for colorectal cancer. A randomized controlled trial is required to verify these results.
ACKNOWLEDGMENTS
We would like to thank Editage (www.editage.co.kr) for English language editing.
Footnotes
Funding: This research was supported by grants of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI23C159101) and the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (RS-2023-CC140354).
Disclosure: The authors have no potential conflicts of interest to disclose.
- Conceptualization: Ku GY, Park JW.
- Data curation: Ku GY, Kim BJ, Park JW, Kim MJ, Ryoo SB, Jeong SY, Park KJ.
- Formal analysis: Ku GY, Park JW.
- Investigation: Ku GY, Kim BJ, Park JW.
- Methodology: Ku GY, Kim BJ, Park JW.
- Software: Ku GY, Park JW.
- Validation: Ku GY, Park JW.
- Writing - original draft: Ku GY.
- Writing - review & editing: Ku GY, Kim BJ, Park JW, Kim MJ, Ryoo SB, Jeong SY, Park KJ.
SUPPLEMENTARY MATERIALS
SSI types and management
Postoperative complications
Univariate analysis for risk factors of surgical site infection
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
SSI types and management
Postoperative complications
Univariate analysis for risk factors of surgical site infection