Role of oral and intravenous pre-operative antibiotics in elective colon surgery

Pre-operative antibiotic administration remains a controversial issue in colorectal surgery. The high bacterial burden of the colon predisposes patients undergoing colorectal surgery to develop surgical site infections (SSI). The increased morbidity and healthcare costs associated with these SSI has further heightened the need for high quality studies to determine the most efficacious practices. Currently, the majority of healthcare practitioners employ a combination of oral antimicrobials and mechanical bowel prep to decrease the bacterial burden within the colon. However, the use or oral antibotics are controversial and there consequently is not one accepted standardized routine in current clinical practice. In the May 2016 issue of British Journal of Surgery (epub ahead of print), Ikeda and colleagues proposed an intriguing article: “Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection” to compare the use of oral and IV antibiotics versus IV antibiotics alone (1).

In order to investigate the use of pre-operative antibiotics in laparoscopic colon cancer patients, the authors conducted a single center study in Japan of 515 cancer patients randomly assigned to two different treatment groups: group 1 combined oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group, n=255) or group 2 perioperative intravenous antibiotics (cefmetazole) alone (IV-only group, n=256). Patients were well-matched in terms of pre-operative characteristics, including type of operation (colonic surgery, anterior resection, or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy, and pre-existing diabetes mellitus.

The primary endpoint was the overall rate of SSI at 30 days after surgery with secondary endpoints of incisional site infection rate, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events, and postoperative complications. The authors found no difference in the incidence of SSI between the two groups. In addition, there was no statistical difference in secondary outcomes (P>0.05). Thus, the authors concluded that IV antibiotics alone before laparoscopic colon surgery is an acceptable practice.

This study is unique in that the investigators specifically looked at laparoscopic colon surgery, which already has an established lower rate of SSIs compared to open colon surgery (2). The authors hypothesized that the use of pre-operative antibiotics is unnecessary for laparoscopic procedures in patients undergoing colon resection for cancer. This could help to decrease associated healthcare costs and also avoid complications associated with antibiotic use, including Clostridium difficile colitis and disruption of the normal bacterial flora of the colon. Thus, the reduced use of pre-operative antibiotics in the study population could have significant effects on healthcare costs.

There are several limitations of the study by Ikeda and colleagues. First, the authors used an absorbable antibiotic (metronidazole) combined with a non-absorbable antibiotic (kanamycin). This combination differs from the original oral bowel prep proposed by Nichols and Condon (3). Oral metronidazole is problematic as metronidazole is absorbed by the gastrointestinal tract and has both an intraluminal and systemic effect (4). Another issue was the inconsistent use of mechanical bowel prep by patients enrolled in the study prior to surgery. The use of mechanical bowel prep remains controversial. Several recent studies have demonstrated improved outcomes when employing pre-operative antibiotics when combined with mechanical bowel prep or antibiotics alone (5-7) while other studies have failed to demonstrate an effect (8). Thus, this confounding factor could have affected the validity of the results of the study. Finally, the authors report the overall SSI rate of their study is significantly lower compared to other studies, which may make these results less generalizable to other patient populations.

Several previous randomized controlled clinical trials have been conducted on this topic previously (9,10). Bellows and colleagues conducted a large meta-analysis of RCTs to compare the effectiveness of combined oral non-absorbable and intravenous antibiotics to reduce SSIs (9). The results of this study found that patients receiving a combination of oral and IV antibiotics had decreased SSIs compared to patients receiving only IV antibiotics. Thus, the authors concluded that both oral non-absorbable and IV antibiotics are necessary. However, this analysis included studies that combined laparoscopic and open surgical procedures. Also, the protocol of antibiotic regiments was not standardized. Thus, the need for a prospective randomized clinical trial investigating a standard pre-op antibiotic regiment in patients undergoing elective laparoscopic colon surgery remains necessary. Furthermore, a recent meta-analysis by Nelson and colleagues confirmed the results of Bellows et al., but did not give specific recommendations on pre-operative antibiotic regiments.

In conclusion, the data supporting the use of a universal pre-operative oral antibiotic regiment and route of administration for colorectal surgery remains unclear. Ikeda and colleagues present a well-designed study that further investigates this topic, specifically in laparoscopic surgery, which always has a lower rate of SSI that contributes to the existing body of literature. However, additional prospective randomized studies are needed to further elucidate the most efficacious strategy to improve post-operative outcomes in colorectal surgery.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Laparoscopic and Endoscopic Surgery. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/ales.2016.12.08). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Ikeda A, Konishi T, Ueno M, et al. Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection. Br J Surg 2016;103:1608-15. [Crossref] [PubMed]
2. Aimaq R, Akopian G, Kaufman HS. Surgical site infection rates in laparoscopic versus open colorectal surgery. Am Surg 2011;77:1290-4. [PubMed]
3. Nichols RL, Condon RE. Preoperative preparation of the colon. Surg Gynecol Obstet 1971;132:323-37. [PubMed]
4. Idkaidek NM, Najib NM. Enhancement of oral absorption of metronidazole suspension in humans. Eur J Pharm Biopharm 2000;50:213-6. [Crossref] [PubMed]
5. Fry DE. Antimicrobial Bowel Preparation for Elective Colon Surgery. Surg Infect (Larchmt) 2016;17:269-74. [Crossref] [PubMed]
6. Chen M, Song X, Chen LZ, et al. Comparing Mechanical Bowel Preparation With Both Oral and Systemic Antibiotics Versus Mechanical Bowel Preparation and Systemic Antibiotics Alone for the Prevention of Surgical Site Infection After Elective Colorectal Surgery: A Meta-Analysis of Randomized Controlled Clinical Trials. Dis Colon Rectum 2016;59:70-8. [Crossref] [PubMed]
7. Eskicioglu C, Forbes SS, Fenech DS, et al. Preoperative bowel preparation for patients undergoing elective colorectal surgery: a clinical practice guideline endorsed by the Canadian Society of Colon and Rectal Surgeons. Can J Surg 2010;53:385-95. [PubMed]
8. Güenaga KF, Matos D, Wille-Jørgensen P. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev 2011;CD001544 [PubMed]
9. Bellows CF, Mills KT, Kelly TN, et al. Combination of oral non-absorbable and intravenous antibiotics versus intravenous antibiotics alone in the prevention of surgical site infections after colorectal surgery: a meta-analysis of randomized controlled trials. Tech Coloproctol 2011;15:385-95. [Crossref] [PubMed]
10. Nelson RL, Gladman E, Barbateskovic M. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database Syst Rev 2014;CD001181 [PubMed]