Surgeons have long believed that wound contamination by colonic stool and bacteria contributes to the development of postoperative infection. While it is intuitive that exposure of the peritoneum and incision to fecal pathogens is an infectious risk, bacteriologic and clinical data have also accumulated in support of this notion. Clean operations carry a markedly lower risk of wound infection than clean-contaminated or contaminated procedures in which the peritoneum is exposed to the contents of the gastrointestinal (GI) tract. Isolates from such wound infections reveal primarily fecal organisms [3].

Accordingly, surgeons have taken measures to decrease the stool and bacterial burden of the colon prior to operation. Mechanical bowel preparation (MBP) is the primary means of reducing colonic fecal content, but does not significantly reduce bacterial concentrations [4]. Orthograde bowel irrigation may be accomplished with large-volume electrolyte solutions, osmotic load, or promotility agents. Retrograde evacuation of the colon and rectum with enemas may complement an oral regimen or serve as stand-alone therapy. Oral antibiotics are added to diminish the bacterial burden in the colon.

The primary intended benefit of MBP in colorectal surgery is a reduction in the incidence of SSIs. Preoperative evacuation of stool allows for operation on a nondistended colon, which may decrease the likelihood of intraoperative spillage of bowel contents and resultant exposure of sterile tissue to fecal bacteria. Oral antibiotics minimize the risk of infection related to any gross or microscopic contamination that does occur. MBP also has advantages unrelated to reduction of infectious risk. Palpation for mass lesions within the colon is more sensitive and accurate in the absence of solid stool. An empty rectum also facilitates passage of an endorectal stapling device or endoscope.

Conversely, MBP has multiple potential disadvantages. Liquid colon contents after MBP may actually be more prone to intraoperative spillage than solid stool [5]. Structural and inflammatory changes within the bowel wall have been attributed to MBP, but only inconsistently demonstrated in studies [6–8]. Compromised integrity of the bowel wall or mucus barrier may contribute to anastomotic leak, bacterial translocation, and postoperative ileus. Alteration in colonic flora by oral antibiotics has the potential to exacerbate these effects, and could be associated with complications such as Clostridium difficile colitis. Furthermore, oral irrigating agents are associated with acid-base imbalance, electrolyte derangements, and hypovolemia, all of which are particularly problematic in elderly patients. Finally, MBP is a source of significant patient discomfort, often causing vomiting, diarrhea, bloating, and cramping.

The process of evaluating the overall value of MBP, with its array of beneficial and detrimental effects, has taken more than 50 years. Still, the optimal roles of MBP and oral antibiotics in colorectal surgery remain incompletely defined. Continued investigation is guided by existing evidence, both historical and contemporary.

The origins of the preoperative bowel preparation remain obscure, but by the 1930s MBP had become well established as the standard of care for colon surgery. Early regimens included various combinations of dietary restriction, enemas, and cathartics such as castor oil. Administration occurred in the hospital over the course of several days before the operation. This type of preparation was widely believed to reduce infections and anastomotic leak rates. It was also preferred for aesthetic reasons.

The discovery of penicillin in 1929 and its subsequent introduction into clinical practice generated interest in the use of antibiotics to prevent as well as treat SSIs. Surgeons rapidly adapted these concepts to colorectal operations, where septic complications occurred in more than 3 out of 4 patients [9,10]. Attempts were made to sterilize the colonic lumen with an oral antibiotic prior to surgery in hopes of preventing postoperative infection. Early antibiotics were not well suited to this purpose, primarily due to an inadequate spectrum of activity against colonic flora and the development of resistant organisms. Nonetheless the theory endured, and surgeons continued to seek a suitable antibiotic.

One such surgeon enumerated the properties that would characterize the ideal antibiotic for oral prophylaxis in colon surgery [10]. A suitable antibiotic would rapidly eradicate colonic microbes without promoting overgrowth of resistant organisms or impeding anastomotic healing. It would be well tolerated by patients and poorly absorbed, with few systemic effects (Box 1) [10]. Following its introduction in 1949, neomycin was recognized as a strong potential candidate antibiotic [11]. Laboratory and clinical evaluation revealed limited systemic absorption with excellent efficacy against colonic gram-positive and gram-negative bacteria [11–13]. Case series and small trials documented low rates of septic complications and adequate patient tolerance of the regimen [11–16]. Combination regimens including nystatin or sulfa-based antibiotics were also investigated, with favorable results [13]. Although these early reports were promising, concern for the risk of antibiotic-associated Staphylococcus aureus enterocolitis prevented the establishment of oral prophylactic antibiotics as a preoperative standard [17].

In 1972, this standard was called into question when Nichols and colleagues [18] published a prospective, randomized, controlled trial evaluating the efficacy of different preoperative bowel preparation regimens. Comparison of microbial burden in the GI tract revealed significantly lower bacterial counts in patients receiving MBP with neomycin and erythromycin than those receiving other antibiotic combinations, MBP alone, or no bowel preparation. The same investigators subsequently demonstrated a reduction in postoperative wound infections for patients treated with a combination of MBP and neomycin-erythromycin before elective colon resection (Box 2) [19]. The rate of SSI was reduced from nearly 20% in patients receiving MBP alone to 0% of 69 patients receiving neomycin-erythromycin, without evidence of staphylococcal or other bacterial overgrowth [19]. Results from these trials prompted a renewed interest in oral antibiotics as an adjunct to MBP.

Box 2 Nichols preoperative bowel preparation

• Day 1:

Low-residue diet

Oral bisacodyl

• Day 2:

Low-residue diet

Magnesium sulfate by mouth 3 times a day

Saline enemas

• Day 3:

Clear liquid diet

Intravenous fluids as needed

Magnesium sulfate by mouth twice a day

Neomycin 1 g by mouth 3 times a day

Erythromycin 1 g by mouth 3 times a day

• Day 4: Operating room

Data from Nichols RL, Broido P, Condon RE, et al. Effect of preoperative neomycin-erythromycin intestinal preparation on the incidence of infectious complications following colon surgery. Ann Surg 1973;178(4):453–62.

Over the course of the following decade, the superiority of MBP with appropriate oral antibiotics was confirmed in other studies, including several multicenter randomized trials [3,9,20–24]. Improvements were documented in the rates of general infectious complications, SSI, abscess, and anastomotic leak. These findings firmly established MBP with oral antibiotics as the gold-standard preparation for elective colon resection.

Investigation of systemic antibiotics for prophylaxis in colon surgery occurred in parallel with research on oral antibiotics. Early trials of intravenous systemic antibiotics in the 1950s failed to definitively establish a significant difference in infectious complications [25]. In hindsight, this lack of benefit was likely a result of postoperative rather than preoperative antibiotic administration. A decade later, systemic antibiotics were reevaluated. Using perioperative dosing, prophylactic intravenous antibiotics covering intestinal flora were found to significantly decrease the risk of SSI in GI tract operations [26]. Comparison of colon surgery with systemic versus oral prophylactic antibiotics demonstrated the lowest morbidity rates in patients receiving a combination of both (Fig. 1) [27,28]. The use of combination oral and systemic antibiotic prophylaxis led to renewed interest in the risk of antibiotic-associated colitis such as that caused by C difficile overgrowth. An actual increase in the risk of C difficile colitis with combination regimens has been reported only in select studies [29,30]. Nonetheless, concern over C difficile, coupled with surgeon confidence in the efficacy of systemic antibiotics, generated a reluctance to use combination prophylaxis. Consequently, the use of oral antibiotics declined.

Fig. 1

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