Bowel preparation for elective colorectal surgery typically consists of mechanical bowel prep, oral antibiotics, and intravenous antibiotics. Mechanical bowel prep is discussed elsewhere; this chapter focuses on perioperative antibiotics for colorectal surgery. Other surgeries for which antibiotic bowel preparation is commonly used include abdominal and pelvic operations involving the aorta, kidneys, bladder, and reproductive structures.

Infectious complications are the leading cause of morbidity and mortality in colorectal surgery. The most common infectious complications include wound infection, intra-abdominal or pelvic abscess, and anastamotic leaks. Offending micro-organisms are typically endogenous colonic flora and include Bacteroides fragilis, Clostridia, Escherichia coli, Klebsiella, Proteus, and Pseudomonas. The logical goals of perioperative antibiotics include decreasing fecal load and bacterial count in the colonic lumen and achieving therapeutic tissue levels of antibiotics in the event that contamination occurs.

Oral antibiotics act on colonic flora intralumenally to decrease bacterial load when the lumen is opened, promoting less contamination and fewer infectious complications. Although there are many conflicting studies on the utility of oral antibiotics in this setting, >70% of surgeons use them as part of their bowel preparation. A combination of neomycin plus erythromycin or metronidazole are the most commonly used agents. The oral antibiotics used are typically given the day before surgery. At the senior author’s hospital, the regimen includes three doses of erythromycin of 1 g each on the day before surgery. Although some oral antibiotics are not well absorbed from the gut, there is significant systemic absorption of erythromycin following oral administration.

One underappreciated problem that may arise with this protocol is the occurrence of unanticipated drug-drug interactions. Through two distinct mechanisms, erythromycin is likely to raise the blood levels of a large number of other drugs. First, erythromycin is a potent inhibitor of both intestinal and hepatic forms of the most important of the cytochrome P450 enzymes, CYP3A4. As such, it inhibits the metabolism of the broad array of CYP3A4 substrates, leading to increases in the blood levels of such drugs. Significant examples of CYP3A4 substrates include alprazolam, carbamazepine,
cyclosporine, methadone, and quinidine, to name just a few. Second, erythromycin also inhibits the functioning of the extruding P-glycoprotein transporter. Thus, inhibition of this transporter also leads to increased levels of P-glycoprotein substrates, such as carbamazepine, cyclosporine, digoxin, morphine, phenytoin, tacrolimus, and tricyclic antidepressants. Drug toxicities are a clear concern when a patient is taking any of these drugs and they also receive a bowel preparation that includes erythromycin. Additionally, inferential reasoning also implicates metronidazole as a P-glycoprotein inhibitor, so the same toxicity concerns would be present when P-glycoprotein substrates are co-administered with metronidazole.