Are prophylactic antibiotics routinely necessary in laparoscopic adnexal surgery? A multicenter cohort study

Background The benefit of routine prophylactic antibiotics for clean laparoscopic adnexal surgery remains unclear. We evaluated whether pre-incision cefazolin reduces the incidence of 30-day surgical site infections (SSIs), and we identified perioperative risk factors for SSIs.

We conducted a multicenter retrospective cohort study using clinical data from Osaka University and six affiliated hospitals. Among 1,865 patients who underwent laparoscopic adnexal surgery for benign conditions, 1,678 were included after specified exclusions. Patients received either pre-incision cefazolin (n = 1,415) or no prophylaxis (n = 263) according to institutional policy. The primary outcome was the incidence of SSI during the 30-day postoperative interval, classified according to CDC criteria. The association between prophylaxis and SSI was evaluated using inverse probability of treatment weighting (IPTW). Propensity scores were estimated using age, body mass index, diabetes mellitus, endometriosis, and previous abdominal surgery. Risk factors for SSI were assessed using multivariable logistic regression analysis. Exploratory subgroup analyses were performed by repeating the same IPTW procedure within specified subgroups, and procedure-specific supplementary analyses were performed for ovarian cystectomy.

SSI occurred in 1.1% of patients in both groups: 16/1,415 in the cefazolin group and 3/263 in the non-antibiotic group. In IPTW-adjusted analyses, the incidence of SSI did not differ between groups (1.1% vs. 1.2%; p = 0.915). In multivariable analysis, operative time ≥120 min was associated with SSI (adjusted odds ratio [aOR] 3.54, 95% confidence interval [CI] 1.41–8.85). In supplementary analyses restricted to an ovarian cystectomy subgroup, uterine manipulator use was associated with SSI (aOR 4.03, 95% CI 1.26–12.90).

Routine prophylactic cefazolin was not associated with a significantly lower incidence of 30-day SSI after clean laparoscopic adnexal surgery. Given few SSI events and the potential for residual confounding, our findings support further evaluation of a selective rather than routine approach to prophylactic antibiotic use. Similar content being viewed by others Laparoscopic adnexal surgeries—including adnexectomy, ovarian cystectomy, and salpingectomy—are standard procedures for treating benign gynecologic conditions. Compared to laparotomy, these minimally invasive procedures are associated with reduced postoperative pain, shorter hospital stays, and faster recovery [1]. Although clean laparoscopic surgeries generally carry a low risk of surgical site infections (SSIs), the clinical benefit of routine prophylactic antibiotic use remains controversial. We hypothesized that, given the low baseline risk of infection in clean laparoscopic adnexal surgery, routine pre-incision cefazolin would not be associated with a significantly lower incidence of 30-day SSI. In Japan, current guidelines from the Japanese Society of Chemotherapy recommend the preoperative administration of cefazolin for laparoscopic adnexal surgeries [2]. However, this recommendation is weakly evidence-based. By contrast, major international societies such as the American College of Obstetricians and Gynecologists (ACOG) and the Society of Obstetricians and Gynecologists of Canada (SOGC) do not recommend routine prophylaxis for class I (clean) laparoscopic procedures that do not involve entry into the gastrointestinal or genitourinary tract, citing insufficient evidence of benefit [3, 4]. Concerns have emerged regarding the overuse of prophylactic antibiotics. There is a growing global emphasis on antimicrobial stewardship to reduce antibiotic resistance, the risk of allergic reactions, and disruption of normal microbiomes [5,6,7]. Some patients develop SSIs after clean laparoscopic surgery even when prophylaxis is administered. Established patient-related risk factors for SSI include obesity, diabetes mellitus, smoking, and immunocompromised status [7]. This highlights the importance of identifying patient- and procedure-related factors such as operative time, surgical approach, and intraoperative device use that may contribute to SSI risk. There appears to be only one study discussing the necessity of prophylactic antibiotics in clean laparoscopic surgery in gynecology, so the issue is not yet fully established [8]. Therefore, we conducted a multicenter retrospective cohort study to (1) compare the incidence of SSIs between patients who did or did not receive preoperative antibiotics, and (2) identify perioperative risk factors—including operative time, surgical procedure, and device use—associated with postoperative SSI in laparoscopic adnexal surgery. Understanding the relevant risk factors for SSI and which patients would benefit the most from prophylaxis will refine clinical decision-making and provide the surgical care team with more selective risk-based strategies and a clinically targeted approach to antibiotic prophylaxis to optimize outcomes.

Study design and setting We conducted a multicenter retrospective cohort study using a prospectively-maintained perioperative database that aggregates anonymized data for gynecologic surgeries performed at Osaka University and six affiliated hospitals in Japan. We included patients who underwent laparoscopic adnexal surgery for benign disease between January 2020 and December 2023. The study compared 30-day SSI incidence between patients who received pre-incision cefazolin (CEZ group) and those who received no prophylactic antibiotics (non-antibiotic group). Whether to use antibiotics was determined by each facility's policy. This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Participants We included consecutive patients undergoing laparoscopic adnexal surgery for benign indications. We excluded cases with adnexal abscess/pelvic inflammatory disease, conversion to laparotomy or tissue retrieval via transvaginal or small-laparotomy incision, concurrent hysteroscopy, or administration of prophylactic antibiotics other than cefazolin. In six of the participating hospitals, patients routinely received 1–2 g of cefazolin intravenously within 60 min before skin incision, as per institutional protocols. In the remaining hospital, prophylactic antibiotics were not routinely used. No formal sample size calculation was performed because all consecutive eligible patients during the predefined study period were included. Outcomes The primary outcome was SSIs occurring within 30 days postoperatively, classified according to CDC criteria (superficial incisional, deep incisional, organ/space pelvic infection) [9]. The secondary outcome involved identifying risk factors associated with SSIs, including age, body mass index (BMI), diabetes mellitus diagnosis, endometriosis diagnosis, previous abdominal surgery, uterine manipulator use, operative time, and blood loss. Statistical analysis Categorical variables were compared using Fisher's exact test, and continuous variables were analyzed with the Mann–Whitney U test. We fitted multivariable logistic regression models to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for SSI. To estimate the propensity score for prophylactic cefazolin use, we included the following clinically relevant covariates: age, BMI, diabetes mellitus, endometriosis, and previous abdominal surgery. IPTW was then performed using the estimated propensity scores to estimate the average treatment effect. Unstabilized weights were used, and observations with weights greater than 30 were excluded to reduce instability caused by extreme weights. Covariate balance after weighting was assessed using absolute standardized mean differences (ASMDs), with values <0.1 considered indicative of acceptable balance. As a sensitivity analysis, we constructed an alternative propensity score model excluding previous abdominal surgery and repeated the IPTW procedure; these results are presented in Supplementary Table 1. Because IPTW creates a weighted pseudo-population rather than preserving the original sample size, weighted sample counts are presented as pseudo-sample sizes. To identify factors associated with SSI, univariable logistic regression analyses were first performed. Variables with p < 0.05 in the univariable analyses and considered clinically relevant were then entered into the multivariable logistic regression model. Given the small number of SSI events, the multivariable models included only a limited number of variables selected from those that were statistically significant in the univariable analysis or considered clinically relevant, to avoid overfitting. For patient-level covariates, only variables that were consistently recorded across participating institutions were considered; smoking status, immunocompromised status, and nutritional status were not uniformly available. Operative time was dichotomized at 120 min, a prespecified and clinically interpretable threshold intended to distinguish prolonged and potentially more complex procedures from routine laparoscopic adnexal surgery. Exploratory subgroup analyses were performed by repeating the same IPTW procedure after restricting the analytic dataset to each subgroup of interest. Subgroups were defined according to age (< 40 or ≥40 years), BMI (< 25 or ≥25 kg/m2), presence or absence of endometriosis, individual procedure type (laparoscopic ovarian cystectomy, adnexectomy, or salpingectomy), and uterine manipulator use. For each subgroup, propensity scores were re-estimated within the restricted dataset using the same covariates, and weighted comparisons were then performed. Supplementary procedure-specific risk factor analyses were conducted separately for the ovarian cystectomy and adnexectomy groups. Analyses were performed using EZR (version 4.0.2), a graphical user interface for R, and R version 4.3.1. All analyses were based on complete-case data, and there were no missing data for variables included in the primary IPTW analysis. A two-sided p < 0.05 was considered statistically significant. Ethical considerations The institutional review boards of all participating hospitals approved this study, which adhered to the Helsinki Declaration.

Study population Of 1,865 eligible cases, we excluded cases with transvaginal or small-laparotomy specimen retrieval (n = 45), concurrent hysteroscopy (n = 29), adnexal abscess/pelvic inflammatory disease (n = 19), conversion to laparotomy (n = 14), and administration of prophylactic antibiotics other than cefazolin (n = 80). A total of 1,678 patients were included in the final analysis, comprising 1,415 in the CEZ group and 263 in the non-antibiotic group (Fig. 1). Baseline characteristics and outcome Baseline patient characteristics are summarized in Table 1. Median age was 40 years (range, 12–95) in the CEZ group and 41 years (range, 13–85) in the non-antibiotic group. Median BMI was 21.5 kg/m2 (range, 13.5–50.6) in the CEZ group and 20.7 kg/m2 (range, 16.5–32.6) in the non-antibiotic group. Diabetes mellitus was present in 2.2% (31/1,415) of the CEZ group and 0.8% (2/263) of the non-antibiotic group. Endometriosis was present in 19.0% (269/1,415) and 26.6% (70/263), respectively. Previous abdominal surgery was reported in 13.2% (187/1,415) of the CEZ group and 3.0% (8/263) of the non-antibiotic group (Table 1). Overall, 19 SSIs (1.1%) occurred within 30 days: 16/1,415 (1.1%) in the CEZ group and 3/263 (1.1%) in the non-antibiotic group. In the CEZ group, 12 cases were classified as superficial incisional SSI and 4 as organ/space pelvic infection, whereas all 3 cases in the non-antibiotic group were superficial incisional SSI. No deep incisional SSI was observed (Table 3, unweighted analysis). Effectiveness of CEZ for preventing SSI After applying IPTW, the weighted sample sizes were 1672.1 in the CEZ group and 1617.1 in the non-antibiotic group (Table 2). Covariate balance improved substantially after weighting. Mean age was 43.0 years (SD 16.8) in the CEZ group and 43.0 years (SD 14.9) in the non-antibiotic group. Mean BMI was 22.2 kg/m2 (SD 4.1) and 21.8 kg/m2 (SD 3.5), respectively. Diabetes mellitus was present in 2.0% and 1.0%, endometriosis in 20.3% and 19.8%, and previous abdominal surgery in 11.6% and 9.3%, respectively. All absolute standardized mean differences were below 0.1, indicating acceptable covariate balance after weighting (Table 2). In the weighted analysis, the incidence of overall SSI remained similar between the two groups (19.1 [1.1%] in the CEZ group vs 19.8 [1.2%] in the non-antibiotic group; p = 0.915). No clear between-group difference was observed for superficial incisional SSI (14.4 [0.9%] vs 19.8 [1.2%]; p = 0.587). Organ/space pelvic infection occurred only in the CEZ group in the weighted analysis (4.7 [0.3%] vs 0; p = 0.050) (Table 3, weighted analysis). Exploratory subgroup analyses Subgroup analyses using IPTW-adjusted models were performed to compare 30-day SSI incidence between the CEZ group and the non-antibiotic group across specified subgroups defined by age, BMI, endometriosis status, procedure type, and uterine manipulator use (Supplementary Table 2). No statistically significant differences in SSI incidence were observed between the two groups in any examined subgroups. Across these subgroup analyses, IPTW-adjusted odds ratios for SSI generally remained close to 1.0, and confidence intervals included the null value. In several strata, estimation was not possible because of the absence of events in one or both groups (not estimable; NE). Overall, these exploratory IPTW analyses did not identify a clear subgroup in which prophylactic cefazolin was consistently associated with a reduction in SSI incidence (Supplementary Table 2). Perioperative factors associated with SSI The results of the univariable analyses of SSI and perioperative factors are shown in Table 4. Uterine manipulator use and operative time ≥120 min were associated with SSI in the univariable analyses. The results of the multivariable logistic regression analysis are shown in Table 5. In the multivariable model, operative time ≥120 min was the factor most strongly associated with SSI (aOR 3.54, 95% CI 1.41–8.85), whereas uterine manipulator use showed a positive trend but was not independently associated (Table 5). Procedure-specific supplementary analyses Separate procedure-specific supplementary analyses were also performed, and the results are shown in Supplementary Tables 3–5. In supplementary analyses restricted to the ovarian cystectomy subgroup, uterine manipulator use was associated with SSI (aOR 4.03, 95% CI 1.26–12.90) (Supplementary Table 4). In the adnexectomy subgroup, operative time ≥120 min was the factor most strongly associated with SSI (aOR 5.13, 95% CI 0.85–31.00) (Supplementary Table 5).

In this multicenter cohort of 1,678 patients undergoing laparoscopic adnexal surgery for benign conditions, the 30-day SSI rate was uniformly low (1.1%) and did not differ between patients who received pre-incisional cefazolin and those who received no prophylactic antibiotics. IPTW-adjusted and exploratory subgroup analyses likewise did not identify a statistically significant reduction in SSI associated with prophylactic cefazolin. In contrast, prolonged operative time (≥ 120 min) was identified as the only independent factor associated with SSIs. Surgical wounds are classified by a system developed by the National Academy of Sciences and the National Research Council based on the degree of expected microbial contamination during surgery [10]. It stratifies wounds as class I (Clean), class II (Clean-contaminated), class III (Contaminated), or class IV (Dirty-infected). Several studies have found a moderate correlation between the wound classification and the SSI rate. SSI rates according to wound class were: class I, 1.3 to 2.9%; class II, 2.4 to 7.7%; class III, 6.4 to 15.2%; class IV, 7.1 to 40.0% [11, 12]. A systematic review showed that prophylactic antibiotics may be effective in reducing SSI across various types of surgery, although no significant benefit was observed in laparoscopic cholecystectomy [13]. Therefore, research is needed on the occurrence of SSIs in laparoscopic surgery and the necessity of prophylactic antibiotic administration other than laparoscopic cholecystectomy. Laparoscopic adnexal surgery is classified as class I (Clean) surgery and is considered to have a low risk of infection. The study by Khalfay et al. [8] is, to our knowledge, the only study to date examining the efficacy of antibiotics in class I laparoscopic gynecologic surgeries. They reported no reduction in SSIs with prophylaxis in minimally invasive procedures (SSI incidence in an antibiotic group versus a no-antibiotic group: 4.1% vs. 5.7%, OR 0.71; CI 0.26–1.94, p = 0.5014), whereas a significant benefit was observed in open surgery (antibiotic group and no-antibiotic group: 6.3% vs. 17.4%, OR 0.32; CI 0.12–0.85, p=0.0223). Our study expands upon these observations by analyzing, to our knowledge, one of the largest multicenter cohorts of laparoscopic adnexal surgeries to date and by using IPTW to improve balance in measured patient-level characteristics. The observed 1.1% SSI rate aligns with prior single-center studies of similar patient populations [8], reinforcing that clean laparoscopic adnexal surgery is inherently low risk for SSIs. The results of our multivariable logistic regression analysis showed that prolonged operative time (≥ 120 min) was the only independent factor associated with SSIs. Similar results have been suggested in systematic reviews [13]. The association between longer operative time and SSIs aligns with biologic plausibility (greater tissue exposure, fluid shifts, and device bioburden) and with emerging analyses suggesting increased SSI/readmission risk after clean gynecologic laparoscopy when procedures are prolonged [14]. Although operative time ≥120 min was associated with SSI, our study did not evaluate whether prophylactic antibiotic administration specifically in prolonged procedures reduces infection risk. Accordingly, operative duration should be regarded as a potential risk marker rather than a validated threshold for initiating prophylaxis. Our exploratory analyses suggested a possible association between uterine manipulator use and SSI in the ovarian cystectomy subgroup. A plausible mechanism is an ascending pathway: intrauterine manipulation may facilitate inoculation of vaginal/cervical flora toward the peritoneal cavity through the fallopian tubes. This hypothesis is consistent with the findings that the use of a manipulator was not a risk factor in the adnexectomy group involving salpingectomy but was a risk factor in cystectomy with fallopian tube preservation. To date, no studies have investigated the relationship between the use of a uterine manipulator and SSIs, so further research is needed. The association between uterine manipulator use and SSI in the ovarian cystectomy subgroup should be considered exploratory and hypothesis-generating. The small number of events and the possibility of residual confounding preclude causal inference. The strengths of this study include its large multicenter design (which enhances its generalizability), the use of IPTW to improve balance in measured patient-level characteristics, consistent outcome definitions based on CDC criteria [7], and a focus exclusively on clean laparoscopic adnexal surgery. Limitations include the retrospective design and small number of SSI events, which may limit statistical power and preclude inclusion of all relevant covariates in multivariable models. Residual confounding factors (e.g., smoking status, glycemic control, immunocompromised status) could not be fully accounted for. In addition, because the no-antibiotic group was derived from a single institution, residual confounding factors related to institution- or surgeon-specific factors could not be fully excluded. Relevant factors such as surgical volume, surgeon experience, operative technique, skin preparation, wound closure methods, operating-room environmental conditions, including room temperature, and SSI surveillance protocols were not uniformly captured in the database and could not be incorporated into the adjusted analyses. Additionally, intraoperative contamination and microbiological data were not available for analysis. Given the very low overall SSI rate and the absence of a statistically significant reduction in SSI associated with prophylactic cefazolin, our findings support further evaluation of a selective, risk-based approach to prophylactic antibiotic use in clean laparoscopic adnexal surgery. Operative time ≥120 min was associated with increased SSI risk; however, our data do not establish whether antibiotic prophylaxis is beneficial specifically in prolonged procedures. This approach aligns with the goals of antimicrobial stewardship, while also minimizing microbiome disruptions and risk of allergic reactions by reducing unnecessary antibiotic use while still preserving patient safety. Uterine manipulator use may also be associated with SSI in the ovarian cystectomy subgroup and warrants further evaluation. Future prospective studies are needed to validate risk thresholds, such as operative times, and to evaluate the utility of targeted prophylaxis. Additionally, development and validation of individualized SSI risk prediction models—such as the Surgical Site Infection Risk Score (SSIRS), which estimates SSI risk based on patient and surgical characteristics—could further refine selective prophylactic strategies in gynecologic laparoscopy [15].

Among predominantly low-risk patients undergoing clean laparoscopic adnexal surgery, prophylactic cefazolin was not associated with a significantly lower incidence of 30-day SSI. Given the small number of SSI events and the potential for residual confounding, these findings do not establish that prophylaxis is unnecessary in all patients. Rather, they support further evaluation of a selective, risk-based approach to prophylactic antibiotic use. Data availability The datasets generated and analyzed during this study are not publicly available due to institutional restrictions on patient data, but they are available from the corresponding author upon a reasonable request and pending ethics approval by the participating centers.

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We acknowledge English proofreading by Gregory S. Buzard, Ph.D. Funding Open Access funding provided by Oita University. This research received no external funding. Author information Authors and Affiliations Corresponding author Ethics declarations Disclosures Dr. Michiko Kodama has received honoraria for lectures from Otsuka Pharmaceutical Co., Olympus Corporation, and Johnson & Johnson. Dr. Kodama also serves as an (unpaid) board member of the Japanese Society of Endoscopy and Robotics in Gynecology and Obstetrics. Drs. Hiromi Miyata, Eiji Kobayashi, Miki Yasuda, Hungwu Chien, Masahiko Takemura, Tomoko Tsujie, Kyoka Amemiya, Akiko Otake, Toshiya Yamamoto, Eiji Nakatani and Yutaka Ueda have no conflicts of interest or financial ties to disclose. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Miyata, H., Kobayashi, E., Yasuda, M. et al. Are prophylactic antibiotics routinely necessary in laparoscopic adnexal surgery? A multicenter cohort study. Surg Endosc (2026). https://doi.org/10.1007/s00464-026-13529-3 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00464-026-13529-3