Oral Antibiotic Preparation Is Associated with Lower Surgical Site Infection After Ileostomy Closure: A Retrospective Cohort Study

Background/Objectives: Surgical site infection (SSI) remains a common complication after ileostomy closure. Mechanical bowel preparation (MBP) and oral antibiotic preparation are often bundled together, so their independent contributions to SSI risk are unclear. We evaluated the adjusted associations of oral antibiotic preparation and MBP with SSI after ileostomy closure, a setting in which these two components have rarely been examined separately. Methods: We retrospectively reviewed 432 consecutive patients undergoing loop or end ileostomy closure at a single center between January 2022 and December 2025. SSI was defined per Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN) criteria. Multivariable logistic regression was used to assess adjusted associations with SSI, with MBP and oral antibiotic preparation included as the exposures of primary interest, adjusting for adjuvant oncologic therapy and closed suction drain use—the covariates associated with SSI on univariate analysis. Results: SSI occurred in 35 patients (8.1%). Oral antibiotic preparation was associated with a lower SSI rate (2.9% vs. 11.5% without; absolute risk reduction 8.5 percentage points, unadjusted descriptive number needed to treat 12; p = 0.003), while no statistically significant unadjusted association was detected for MBP (p = 1.000). After adjustment, oral antibiotic preparation was associated with lower odds of SSI (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.08–0.56; p = 0.002), whereas no statistically significant adjusted association was observed for MBP (OR, 1.21; 95% CI, 0.58–2.53; p = 0.610); this confidence interval is compatible with both a clinically meaningful benefit and a clinically meaningful harm of MBP, and the study is not powered to exclude either. Adjuvant oncologic therapy (OR 2.53, 95% CI 1.23–5.20) and closed suction drain use (OR 2.33, 95% CI 1.14–4.77) were associated with higher adjusted odds of SSI. The model showed acceptable discrimination (area under the receiver operating characteristic curve [AUC] = 0.745), with no evidence of poor fit on a covariate-pattern-based goodness-of-fit assessment (χ2 = 11.37, df = 14, p = 0.657). A Firth penalized-likelihood model, used because of the limited number of events in the antibiotic-exposed group, gave materially unchanged estimates (OR 0.23, 95% CI 0.09–0.58). Conclusions: Oral antibiotic preparation was associated with lower adjusted odds of SSI after ileostomy closure, whereas the association with MBP remained inconclusive. This observational association should not be interpreted as evidence of causality, because residual confounding—particularly by surgeon-level practice—cannot be excluded. These findings should be considered hypothesis-generating and require confirmation in prospective studies using standardized preparation protocols.