Colorectal cancer

Mechanical bowel preparation with or without antibiotic prophylaxis

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Background[edit source]

Patients undergoing surgery for colorectal cancer have a significant risk of surgical site infections, with their associated health care costs and poor outcomes. In the last 100 years many interventions have been used in attempts to modify this risk.[1][2] Surgical site infection rates and anastomotic leak rates have become important clinical indicators used to measure hospital and unit outcomes, and even guide reimbursement, particularly in the USA. Surgical site infection reduction programs or ‘bundles’ are increasingly a focus for policy makers.

Mechanical bowel preparation (MBP) involves an oral laxative solution to cleanse the colon of faecal contents, and has been thought to reduce the number of bacteria in the bowel, and thus lower the risk of infective complications such as wound infection and anastomotic leak after colorectal surgery including cancer surgery.[1] Three main types of MBP are used currently, including sodium picosulfate, polyethylene glycol (PEG) and sodium phosphate, with no clear evidence to suggest one format is better than the others, although PEG may be better in patients who cannot tolerate electrolyte imbalances.[1]

MBP has been used routinely throughout the 21st century. However, in the last four decades, a number of publications have published results suggesting that MBP may not be necessary and in fact may even have a deleterious effect on patient outcomes.[3][4][5] A Cochrane review was originally published on this issue in 2004, and has subsequently been reviewed twice with additional papers included.[6] The most recent review published in 2011, included 18 studies with 5805 patients, comparing patients receiving MBP with those receiving no MBP.[7] It also included a small group where patients receiving MBP were compared to those only receiving an enema. The authors were unable to show any difference in anastomotic leak rates or wound infection rates between the groups.[7] This led to guidelines from a number of colorectal groups suggesting that MBP should be abandoned for most cases, particularly in colonic surgery.[8][9][7] Despite this, many surgeons still use MBP, particularly for rectal resections.

Antibiotics in one form or another have been used in colorectal surgery since the 1930s, and prophylactic administration of antibiotics has been well documented to decrease morbidity, shorten hospital stay and reduce infection-related costs.[10][11][12] There appears to be no advantage with multiple doses of intravenous antibiotics compared to a single dose of antibiotic.[13] However, cover should be provided against aerobic and anaerobic bacteria.[12]

In the early 1970s, Nichols and Condon popularised a combination of oral and intravenous antibiotics,[2] which was particularly popular in the USA.[14] However, for a variety of reasons, including poor compliance and increased day of surgery admission, this has been replaced in many regions in the last two decades by intravenous antibiotics given prophylactically at operation.[15]

Some centres, particularly in the USA, have continued to use routine preoperative oral antibiotics, with neomycin and erythromycin most commonly used, although metronidazole, ciprofloxacin and aminoglycosides are also employed. Interestingly, in the last 2 years a number of retrospective studies, some including very large data sets from North America, have published results, which suggest a clear benefit with reduced rates of surgical site infections in patients given preoperative oral antibiotics and intravenous antibiotics in combination with mechanical bowel preparation, in comparison to those patients not given oral antibiotics regardless of whether they took MBP or not.[16][17][18][19][20][21]

Analysis of a large cohort of patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) reported that patients receiving oral antibiotics in addition to intravenous antibiotics and MBP, also had improved outcomes in other areas in addition to a lower surgical site infection rate, with reduced rates of anastomotic leakage and postoperative ileus on multivariate analysis.[17] The improvements in outcomes were not seen in patients taking preoperative oral antibiotics and intravenous antibiotics if they did not receive MBP.

Recent WHO Guidelines on surgical site infection prevention[22] suggested that oral antibiotics should be used routinely in combination with mechanical bowel preparation in patients undergoing elective colorectal surgery. This was a conditional recommendation on the basis of firstly examining studies comparing MBP with oral antibiotics compared to MBP without oral antibiotics, and secondly another comparison of patients receiving MBP compared to no MBP.[22] No RCT has yet been completed directly comparing patients receiving MBP, with oral and IV antibiotics with no MBP. Two studies are currently recruiting, one in Finland[23] and one in the USA[24], examining this question.

One recently published Japanese study randomised 515 patients receiving laparoscopic surgery for colorectal cancer, comparing 255 patients receiving preoperative oral antibiotics and intravenous antibiotics to 256 patients only receiving intravenous antibiotics.[25] They found no difference in any of the outcomes studied particularly SSI rates, which were 7.8% in each group, however not all patients in this study received MBP.[25]

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Systematic review evidence[edit source]

In patients diagnosed with colorectal cancer and undergoing surgical tumour resection, does mechanical bowel preparation with or without antibiotic prophylaxis, when compared to usual care, achieve better outcomes in terms of anastomotic leakage, surgical site infection, length of hospital stay and ileus?

Fourteen level II randomised controlled trials (RCTs) were analysed examining the effect of MBP (with antibiotic prophylaxis) compared with no MBP (with or without antibiotic prophylaxis) in colorectal cancer.[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]

All of the RCTs were at high risk of bias, and they were from a variety of different countries in Europe and Asia, where quality of colorectal cancer treatment may be comparable to the Australian population.[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] One study performed in Western Australia was directly applicable to Australian colorectal cancer patients.[35]

Outcomes of interest analysed included anastomotic leakage/dehiscence, surgical site/wound infection (including abscess), postoperative ileus and length of hospital stay.

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Anastomotic leakage/dehiscence[edit source]

Ten RCTs and one subgroup analysis reported overall anastomotic leak rates when comparing MBP (with antibiotic prophylaxis) to no MBP (with or without antibiotic prophylaxis) with postoperative follow up ranging from 24 days to 3 months.[26][27][28][29][31][32][33][35][36][38][41] No trial showed a statistically significant difference in anastomotic leak rate.

One trial[26] marginally favoured no mechanical bowel preparation, while two further trials}}[27][38] favoured mechanical bowel preparation, however these were trends and not statistically significant. The trials that did report small differences between groups were for the outcome of overall anastomotic leakage and tended to have lower participant numbers than those reporting none to negligible differences between groups. Subgroup analysis looking at low anterior resection, stapled and hand sewn anastomoses showed no difference between groups.[39]

Four RCTs looked at the rate of clinically significant anastomotic leakage/dehiscence, and showed no statistically different difference between the groups with and without MBP.[27][28][29][35]

One trial from Western Australia, compared patients receiving MBP (with PEG) to patients receiving a phosphate enema and found a trend favouring mechanical MBP with patients experiencing lower rates of anastomotic leaks in the MBP group (2% versus 4.8%).[35] In this study, the clinical anastomotic leak rate in the MBP group was lower than in the no-MBP group (0.7% versus 4.1%: odds ratio (OR) 1.75; 95% confidence interval (CI) 0.02 to 1.35, p = 0.06). This did not reach statistical significance, however there was a significant difference between the groups in the number of patients requiring reoperations for anastomotic leaks (0% versus 4.1%: odds ratio (OR) 2.1; 95% confidence interval (CI) 1.83 to 2.30, p=0.01) The authors of this study were concerned regarding this finding and used this information on reoperation to terminate their study prematurely.

Similarly, another group reported a trend to lower rates of clinically significant anastomotic leakage for those undergoing MPB than no MPB (7.0% versus 16.0%). However, the statistical significance was not reported.[28] There was a non-significant trend for reduced anastomotic leakage/dehiscence rates in a subgroup of patients with diverting loop ileostomies receiving MBP than those receiving no MBP (0.0% versus 4.8%; p-value NS).[39]

Three RCTs[27][28][29] and one subgroup analysis[39] reported asymptomatic or minor anastomotic leakage and found no statistically significant differences between patients receiving MBP (with antibiotic prophylaxis) compared with no MBP (with or without antibiotic prophylaxis).

Surgical site infection[edit source]

Overall wound infection rates[edit source]

Seven RCTs[35][36][37][28][41][29][37][33] and one subgroup analysis[39] examined overall wound infection rates, and found no statistically significant difference in overall wound infection rates comparing patients taking MBP (with antibiotic prophylaxis) with those taking no MBP (with or without antibiotic prophylaxis).

There were some non-significant trends to better outcomes with MBP in one study with four arms when patients added synbiotics to MBP and oral antibiotics[34], and in another study in patients who had a diverting loop ileostomy.[39] In contrast, another study showed a non-significant trend to lower overall surgical site infection rate in patients with no MBP compared with MBP (29.2% versus 17.2%, p-value NS).[33]

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Deeper abdominal, intra-abdominal or wound abscess[edit source]

Six RCTs[26][27][28][31][35][41] and one subgroup analysis[39] reported deeper abdominal, intra-abdominal or wound abscess rates. Six studies consistently reported minimal to no difference between mechanical bowel preparation (with antibiotic prophylaxis) compared with no mechanical bowel preparation (with or without antibiotic prophylaxis).[27][28][31][35][41] One trial[26]{{ reported a small, non-significant difference in favour of no MBP (with antibiotic prophylaxis) (7.9% versus 3.0%, p = 0.62).

In contrast to the aforementioned trials, one RCT reported significantly lower rates of abscess in the MBP group (with antibiotic prophylaxis) than the no-MBP group (with antibiotic prophylaxis),including for overall intra-abdominal abscess (2.2% versus 4.7%; difference 2.4; 95% CI 0.5 to 4.4; p = 0.02) and abdominal abscess with anastomotic leak (0.3% versus2.5%; difference 2.2; 95% CI 0.9 to 3.4; p = 0.001).[28]

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Organ/space surgical site infection[edit source]

Two RCTs[40][33] reported organ/space surgical site infection rates and one RCT[36] reported intra-abdominal infection rates. There was no significant difference between groups taking MBP and not taking MBP.

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Mild or superficial surgical site/wound infection[edit source]

Seven RCTs[33][40][26][38][31][30][28] and one subgroup analysis[39] reported mild or superficial surgical site/wound infection. No study showed a statistically significant difference in mild surgical site infection rates associated with use of MBP.

Three RCTs[26][33][40] reported lower rates of surgical site infections among those that did not have MBP (with antibiotic prophylaxis), with reductions ranging from 4.8% to 10.7%. However, none of these differences were statistically significant.

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Severe wound infection/subcutaneous wound disruption[edit source]

One RCT[28] and one subgroup analysis of low anterior resection and diverting ileostomy[39] patients reported severe wound infection. Both were consistent in finding no statistically significant differences between MBP (with antibiotic prophylaxis) compared with no MBP (with antibiotic prophylaxis).

A further RCT reported subcutaneous wound disruption rates and also found no significant differences between groups.[31]

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Wound dehiscence[edit source]

One RCT[36] that reported wound dehiscence within 6 weeks post operation and one subgroup analysis[39] of low anterior resection reporting fascia dehiscence were consistent in reporting minimal between group differences.

In contrast, the subgroup analysis of diverting ileostomy reported fascial dehiscence to be higher for the MBP (with antibiotic prophylaxis) group than the no MBP group, but this was not statistically significant (7.4% versus 0.0%; p-value reported as NS).[39]

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Ileus[edit source]

Five RCTs reported on post-operative ileus when comparing groups of patients taking MBP (with antibiotic prophylaxis) with those not taking MBP (with or without antibiotic prophylaxis).[29][31][36][38][40] There was no statistically significant difference in the incidence or duration of ileus between the groups.

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Length of hospital stay[edit source]

Eleven RCTs reported length of hospital stay as an outcome for MBP (with antibiotic prophylaxis) compared to no MBP (with or without antibiotic prophylaxis).[27][28][29][30][31][32][35][36][38][40]

Five trials reported less than a day difference between arms with no statistically significant differences (p-values ranging from 0.4 to 0.73).[28][31][35][36][41] Four trials reported one day difference between arms but were not statistically significant.[27][29][30][32] One further trial[38] reported a 4.4 median day difference between arms, which favoured no MBP (with antibiotic prophylaxis) and similarly another trial[40] also favoured no MBP with a 2 day mean difference between arms. However, differences between groups in both trials were not statistically significant (p-values 0.28 and 0.17, respectively). These latter two trials also contained low patient numbers such that results should be interpreted cautiously.[40][38]
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Evidence summary and recommendations[edit source]

Evidence summary Level References
There is no significant difference in anastomotic leak rate when comparing patients who received MBP to no MBP, regardless of antibiotics administered. II [26], [27], [28], [29], [31], [33], [35], [36], [38], [41]
Overall surgical site infection rates are not significantly altered by the use of MBP, regardless of antibiotics taken.

One study (Contant 2007) did show a significant reduction in the intra-abdominal abscess rate in patients who received MBP.

II [27], [28], [31], [35], [36], [37], [39], [41]
Incidence and duration of postoperative ileus is not impacted by usage of MBP. II [32], [34], [39], [40]
There is no statistically significant difference in hospital stay associated with usage of MBP. II [28], [31], [35], [36], [41], [27], [29], [30], [32], [38], [40]
Evidence-based recommendationQuestion mark transparent.png Grade
Mechanical bowel preparation should not be used routinely in colonic surgery. It can be used selectively according to individual patient and tumour characteristics, at the surgeon’s discretion.

Considerations in making this recommendation[edit source]

Mechanical bowel preparation should not be used routinely in colonic surgery. It can be used selectively according to individual patient and tumour characteristics, at the surgeon’s discretion.

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Health system implications[edit source]

Clinical practice[edit source]

The recommendation to consider mechanical bowel preparation on a case-by-case basis does not represent a significant departure from current practice. A 2011 survey of Australian and New Zealand colorectal surgeons found that routine oral mechanical bowel preparation was preferred by 28% for colon resection and 63% for rectal resection.[42]

Resourcing[edit source]

The recommendation has no implications for resourcing.

Barriers to implementation[edit source]

Surgeons who prefer routine mechanical bowel preparation may continue this practice.

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Discussion[edit source]

Unresolved issues[edit source]

It is not clear if mechanical bowel preparation used in combination with preoperative oral antibiotics and intravenous antibiotics is associated with reduced rates of surgical site infection and anastomotic leak.

Studies currently underway[edit source]

There is a Finnish MOBILE trial currently recruiting which is randomizing patients undergoing elective colectomies to receive either mechanical and oral antibiotic bowel preparation or no bowel preparation, which will hopefully help answer this question.[23]

Future research priorities[edit source]

There are two studies currently recruiting, one from Finland[23] and one from the USA[24], which are randomizing patients undergoing elective colorectal surgery to receive either mechanical bowel preparation and oral antibiotics or no mechanical bowel preparation with oral antibiotics. These studies should help determine the role of mechanical bowel preparation and oral antibiotics in elective colorectal surgery.

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References[edit source]

  1. 1.0 1.1 1.2 Kumar AS, Kelleher DC, Sigle GW. Bowel Preparation before Elective Surgery. Clin Colon Rectal Surg 2013 Sep;26(3):146-52 Available from:
  2. 2.0 2.1 Nichols RL, Condon RE. Preoperative preparation of the colon. Surg Gynecol Obstet 1971 Feb;132(2):323-37 Available from:
  3. Hughes ES, McDermott FT, Polglase AL, Johnson WR, Pihl EA. Sepsis and asepsis in large bowel cancer surgery. World J Surg 1982 Mar;6(2):160-5 Available from:
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  21. Scarborough JE, Mantyh CR, Sun Z, Migaly J. Combined Mechanical and Oral Antibiotic Bowel Preparation Reduces Incisional Surgical Site Infection and Anastomotic Leak Rates After Elective Colorectal Resection: An Analysis of Colectomy-Targeted ACS NSQIP. Ann Surg 2015 Aug;262(2):331-7 Available from:
  22. 22.0 22.1 World Health Organization. Global Guidelines for the Prevention of Surgical Site Infection. WHO; 2016.
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  28. 28.00 28.01 28.02 28.03 28.04 28.05 28.06 28.07 28.08 28.09 28.10 28.11 28.12 28.13 28.14 28.15 28.16 Contant CM, Hop WC, van't Sant HP, Oostvogel HJ, Smeets HJ, Stassen LP, et al. Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial. Lancet 2007 Dec 22;370(9605):2112-7 Available from:
  29. 29.00 29.01 29.02 29.03 29.04 29.05 29.06 29.07 29.08 29.09 29.10 Fa-Si-Oen P, Roumen R, Buitenweg J, van de Velde C, van Geldere D, Putter H, et al. Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery. Dis Colon Rectum 2005 Aug;48(8):1509-16 Available from:
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  35. 35.00 35.01 35.02 35.03 35.04 35.05 35.06 35.07 35.08 35.09 35.10 35.11 35.12 35.13 Platell C, Barwood N, Makin G. Randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol before elective colorectal surgery. Br J Surg 2006 Apr;93(4):427-33 Available from:
  36. 36.00 36.01 36.02 36.03 36.04 36.05 36.06 36.07 36.08 36.09 36.10 36.11 Ram E, Sherman Y, Weil R, Vishne T, Kravarusic D, Dreznik Z. Is mechanical bowel preparation mandatory for elective colon surgery? A prospective randomized study. Arch Surg 2005 Mar;140(3):285-8 Available from:
  37. 37.0 37.1 37.2 37.3 37.4 Reddy BS, Macfie J, Gatt M, Larsen CN, Jensen SS, Leser TD. Randomized clinical trial of effect of synbiotics, neomycin and mechanical bowel preparation on intestinal barrier function in patients undergoing colectomy. Br J Surg 2007 May;94(5):546-54 Available from:
  38. 38.00 38.01 38.02 38.03 38.04 38.05 38.06 38.07 38.08 38.09 38.10 Sasaki J, Matsumoto S, Kan H, Yamada T, Koizumi M, Mizuguchi Y, et al. Objective assessment of postoperative gastrointestinal motility in elective colonic resection using a radiopaque marker provides an evidence for the abandonment of preoperative mechanical bowel preparation. J Nippon Med Sch 2012;79(4):259-66 Available from:
  39. 39.00 39.01 39.02 39.03 39.04 39.05 39.06 39.07 39.08 39.09 39.10 39.11 39.12 39.13 Van't Sant HP, Weidema WF, Hop WC, Oostvogel HJ, Contant CM. The influence of mechanical bowel preparation in elective lower colorectal surgery. Ann Surg 2010 Jan;251(1):59-63 Available from:
  40. 40.00 40.01 40.02 40.03 40.04 40.05 40.06 40.07 40.08 40.09 40.10 Watanabe M, Murakami M, Nakao K, Asahara T, Nomoto K, Tsunoda A. Randomized clinical trial of the influence of mechanical bowel preparation on faecal microflora in patients undergoing colonic cancer resection. Br J Surg 2010 Dec;97(12):1791-7 Available from:
  41. 41.0 41.1 41.2 41.3 41.4 41.5 41.6 41.7 41.8 41.9 Zmora O, Mahajna A, Bar-Zakai B, Hershko D, Shabtai M, Krausz MM, et al. Is mechanical bowel preparation mandatory for left-sided colonic anastomosis? Results of a prospective randomized trial. Tech Coloproctol 2006 Jul;10(2):131-5 Available from:
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Appendices[edit source]

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