Cigdem Benlice, Ipek Sapci, T. Bora Cengiz, Luca Stocchi, Michael Valente, Tracy Hull, Scott R. Steele, Emre Gorgun 07/23/2018

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Does preoperative oral antibiotic or mechanical bowel preparation increase Clostridium difficile colitis after colon surgery? An assessment from ACS-NSQIP procedure-targeted database Cigdem Benlice, Ipek Sapci, T. Bora Cengiz, Luca Stocchi, Michael Valente, Tracy Hull, Scott R. Steele, Emre Gorgun Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, OH 07/23/2018

Disclosures The authors have nothing to disclose relevant to the study

Background Despite the recent literature suggesting that combined use of preoperative oral antibiotic (POAP) and mechanical bowel preparation (MBP) decreases surgical site infections after colorectal surgery, there are concerns that their use may result in decreased bacterial load and could contribute to an increased incidence of hospital-acquired Clostridium difficile colitis (CDC) Leffler DA, NEJM, 2016 Parthasarathy M, Colorectal Dis, 2018 Lee DY, Ann Surg, 2014

Aim To identify the risk factors for postoperative CDC in patients undergoing colectomy and determine whether preoperative oral antibiotic or mechanical bowel preparation increase the risk of CDC

Methods Patients underwent elective colectomy between 2015-2016 from ACS-NSQIP procedure-targeted database Emergency procedures, patients with ASA class-5 and patients who were being treated for Clostridium difficile infection at the time of the principal operative procedure were excluded Patients were divided into two groups (No CDC vs. CDC) The criteria used by NSQIP to identify patients with CDC were a documented record of a positive Clostridium difficile laboratory test or documentation of treatment for Clostridium difficile infection in the 30-day postoperative period. Laboratory tests used to identify postoperative CDC included stool culture, stool cytotoxin, enzyme Immunoassays for toxin A and B, GDH EIA and PCR

Methods Primary outcomes: Predictors of CDC after colectomy Univariate and multivariate regression analyses were conducted to determine predictor variables associated with CDC after colectomy A univariate analysis was conducted assessing the possible relationship between 34 NSQIP preoperative and operative variables and the rates of CDC Variables were selected into the final model using a logistic regression selection procedure with alpha=0.05 stay criteria

A total of 43,668 patients met inclusion criteria Overall 30-day rate of CDC after colectomy was 1.45% Results Demographics and Comorbidities Factor No CDC (N=43,035) Yes CDC (N=633) p-value Age 62.0 [52.0,72.0] 66.0 [54.0,75.0] <0.001 BMI 27.7 [24.0,32.1] 27.8 [24.1,32.6] 0.40 Gender (Female) 22,329 (51.9) 368 (58.1) 0.002 Chemotherapy within 90 Days 2,697 (6.4) 17 (2.7) <0.001 DM 6,680 (15.5) 85 (13.4) 0.15 Current smoker 7,114 (16.5) 119 (18.8) 0.13 COPD 2,037 (4.7) 54 (8.5) <0.001 Ascites 216 (0.50) 8 (1.3) 0.008 HTN 20,420 (47.4) 334 (52.8) 0.008 Preop steroid use 3,838 (8.9) 80 (12.6) 0.001 Bleeding disorders 1,378 (3.2) 34 (5.4) 0.002 Preop transfusion 908 (2.1) 18 (2.8) 0.20 MBP 24,763 (66.7) 351 (62.6) 0.037 OAP 18,405 (48.9) 210 (37.0) <0.001 Combined bowel prep 15,829 (40.6) 179 (30.7) <0.001 ASA classification <0.001 1-No Disturb 848 (2.0) 7 (1.1) 2-Mild Disturb 18,278 (42.5) 213 (33.6) 3-Severe Disturb 21,696 (50.4) 362 (57.2) 4-Life Threat 2,213 (5.1) 51 (8.1)

Results Operative Characteristics Factor No CDC (N=43,035) Yes CDC (N=633) p-value Indication for surgery <0.001 Colon cancer 19,377 (45.0) 262 (41.4) Crohn's Disease 2,610 (6.1) 35 (5.5) Non-malignant polyp 4,173 (9.7) 45 (7.1) Other 6,842 (15.9) 136 (21.5) Ulcerative colitis 861 (2.0) 9 (1.4) Diverticulitis 9,172 (21.3) 146 (23.1) Approach <0.001 Laparoscopic 26,612 (61.8) 347 (54.8) Open (planned) 12,083 (28.1) 229 (36.2) Robotic 4,340 (10.1) 57 (9.0) Principle procedure <0.001 LAR/AR 12,462 (29.0) 152 (24.0) Partial colectomy w anastomosis 15,328 (35.6) 219 (34.6) Partial colectomy w colostomy 2,890 (6.7) 55 (8.7) Right hemicolectomy 10,308 (24.0) 190 (30.0) Total abdominal colectomy 2,047 (4.8) 17 (2.7)

Results Multivariate Analyses for C. difficile infection Variable Odds Ratio (95% CI) Overall P-value Preoperative Mechanical Bowel Prep 1.2 (0.94, 1.4) 0.17 Preoperative Oral Antibiotic Prep 0.63 (0.52, 0.77) <0.001 Age (per 5-year increase) 1.05 (1.01, 1.09) 0.009 Chemotherapy within 90 Days 0.45 (0.26, 0.77) 0.004 History of severe COPD 1.6 (1.1, 2.1) 0.005 Steroid use for chronic condition 1.6 (1.2, 2.2) 0.003 Systemic sepsis 1.4 (1.00, 2.0) 0.048 Indication for surgery 0.003 Colon Cancer 1 - Diverticulitis 1.4 (1.1, 1.9) 0.003 Principle procedure 0.04 Partial colectomy w anastomosis 1 - LAR/AR 0.97 (0.77, 1.2) 0.77 Partial colectomy w colostomy 0.94 (0.66, 1.3) 0.71 Right hemicolectomy 1.3 (1.02, 1.6) 0.03 Total abdominal colectomy 0.62 (0.34, 1.1) 0.12

Limitations Retrospective cohort 30-day outcomes Preoperative antibiotic use History of prior C. difficile infection

Conclusion Neither oral antibiotics nor mechanical bowel preparation increase the risk for Clostridium difficile colitis after colectomy Based on the detailed analysis of this nationwide cohort, both can be used safely in order to decrease surgical site infections after colorectal surgery without increased risk of Clostridium difficile induced colitis