226 The American Journal of Surgery, Vol 202, No 2, August 2011Glenny8 similarly performed a large meta-analysis that Table 1 Provides the requirements of an ideal antibioticconﬁrmed that preoperative administration of the drug is bowel preparation as deﬁned by Pothcritical and that sustained administration of the antibioticfor days after the procedure offers no beneﬁt to the Low toxicity for the hostpatient. The principals established in these studies have Broad antimicrobial spectrum Chemical stability in the presence of digestive enzymesbeen the basis for consensus performance measures that Capacity to prevent overgrowth or development of resistantsubsequently have been developed including those from bacteriathe Surgical Infection Prevention Project and its succes- Rapidity of actionsor the Surgical Care Improvement Project.9,10 Activity in the presence of nutrients Although the academic community of surgery progres- Low absorption from the enteric tract Aid to mechanical cleansing without causing dehydrationsively moved toward a consensus opinion on the role of Nonirritant to enteric mucosasystemic antibiotics, such has not been the case for the use Noninhibitor of healingof colonic preparation. There continues to be confusion Low bacteriocidal dosageabout whether mechanical bowel preparation (MBP) alone Water solubleis of any value in reducing SSI rates, and whether oral Palatable Antifungal activityantibiotics given in the preoperative period in conjunction Use restricted to intestinal antisepsiswith MBP is a useful technique in the prevention of infec-tion. This presentation attempts to review the evolution ofthe strategies to prepare the colon for surgical resection,identify the current evidence for and against MBP and oral concentration of bacteria. Nichols et al12 similarly con-antibiotic preparation, and provide some perspective on the ﬁrmed that MBP alone had no impact on microbial concen-future of colonic preparation that will optimize outcomes tration in the colon. The only conclusion that can be reachedfor these patients. is that there is no clinical or microbiologic evidence to support MBP alone as a method to reduce SSI rates for elective colon surgery.History of Mechanical Colon Preparation The origin of MBP is likely to date from the very Oral Antibiotic Bowel Preparationbeginning of resection as a treatment method for colonicdisease. Reﬁnements in general anesthesiology and the Indeed, from the earliest time of the introduction ofadvent of blood banks in the 1930s resulted in more antibiotics into clinical practice with sulfanilamide prep-venturesome surgical interventions into the microbe- arations in the 1930s, surgical investigators were explor-laden colon and infection became a predominant compli- ing the use of antimicrobials in the lumen of the coloncation. Colon resections from the era of the 1930s were because it was recognized that MBP did not reduce eitheraccompanied by mortality rates of 10% to 12% and had the concentration of bacteria or SSIs.13–15 The severitySSI rates reported to be as high as 80% to 90%.11 From and frequency of infectious complications in colon sur-the beginning of clinical microbiology, it was apparent gery, the availability of new antibiotics that were beingthat the human colon contained an unusually high con- marketed by companies, and the recognition from animalcentration of microbes. Cleansing the colon of gross fecal experiments that dramatic reductions in colonic bacteriamaterial was a logical strategy to reduce microbial con- density could be achieved with oral antibiotics led totamination at the surgical site and thus potentially reduce enthusiastic investigations of intestinal antisepsis.16 Ed-infections. Many surgeons believed that mechanical gar Poth11 became the champion of colonic preparationcleansing enhances the manipulation of the colon within for elective surgical intervention beginning in 1940. Hethe abdomen during laparotomy, but MBP has been pur- recognized from the beginning that MBP was a require-sued principally for its theoretical beneﬁts in the reduc- ment for effective intestinal antimicrobial use, not be-tion of SSI. In many abdominal surgeries in which colon cause it reduced the concentration of bacteria, but be-resection was not a planned part of the procedure, pre- cause the massive colonic burden of intraluminal bacteriaoperative MBP of the colon also was undertaken with the had to be diminished if any antimicrobial action wasassumption that inadvertent colon wounds from dissec- going to occur on the mucosal surface with orally admin-tion could safely be repaired primarily. From the 1930s istered drugs. The vigor of MBP to rid the colon of anythrough the subsequent decades, MBP became a part of retained fecal material often extended for several dayssurgical lore even though no prospective randomized before the actual procedure. He formulated requirementstrials validated the assumption. for the ideal oral antibiotic (Table 1). Succinylsulfathia- As a pioneer in the use of oral antibiotics for colonic zole and Sulfathalidine (phthalsulfathiazole) were drugssurgery, Poth11 noted that although MBP reduced the bur- of choice because of poor absorption, high intraluminalden of total bacteria in the colon, it did not reduce the concentrations, and effective reduction in aerobic bacte-
D.E. Fry Colon preparation and SSI 227 Table 2 Diversity of MBP that has been used in those studies in which the oral antibiotic bowel preparation has been shown to be effective Washington et al,24 1974 Nichols,25 1973 1-day preparation Residue-free diet for 48 h before Day 1, low-residue diet; Bisacodyl, 1 capsule Day before procedure49: 48 g of sodium surgery orally at 6 PM phosphate with Ն2 L of water given Sodium phosphate and Day 2, continue low-residue diet; the day before the procedure; if not biphosphate 16 mL twice daily magnesium sulfate, 30 mL 50% solution clear, then saline enemas until clear for 48 h before surgery (15 g) orally at 10:00 AM, 2:00 PM, and with all completed by 6:00 PM Two tap water enemas 2 d 6:00 PM; Saline enemas in evening until Then, 2 g of neomycin and 2 g of before surgery return clear metronidazole at 7:00 and 11:00 PM Two tap water enemas each on Day 3 clear liquid diet; supplemental or the morning and afternoon of intravenous ﬂuids as needed Day before procedure36: 4 L of the day before surgery Magnesium sulfate, at dose stated earlier, at polyethylene glycol (60 g) and salts 500 mg neomycin and 250 mg 10:00 AM and 2:00 PM (CoLyte®[Alaven Pharmaceuticals, tetracycline taken 4 times/d No enemas Marietta, GA], GoLYTELY®[Braintree for 48 h before surgery Neomycin (1 g) and erythromycin base (1 g) Laboratories, Braintree, MA]) to be at 1:00, 2:00, and 11:00 PM completed by 12:00 PM; then Day 4, surgery scheduled at 8:00 AM neomycin 1 g and erythromycin 1 g at 1:00, 2:00, and 10:00 PMrial species within the colon.17,18 Although these sulfa discussion of the manuscript by Washington et al.24 Thepreparations did not have activity against the anaerobic trial results were dramatic: 43% SSIs in the placebo group,species of the colon, Poth11 believed that disruption of 41% in the neomycin-only group, but only 5% in the neo-the anaerobic environment and the synergistic relation- mycin plus tetracycline group.ship between aerobes and anaerobes would result in an A year before the Washington study, Nichols et al25obligatory reduction in anaerobic concentrations. published a small series (N ϭ 20) with bacteriology results The microbial coverage of the sulfa derivatives subse- that showed both aerobic and anaerobic effectiveness ofquently was considered inadequate, and with the introduc- neomycin and erythromycin base in the colon after MBP.tion of the aminoglycosides, these drugs were considered Erythromycin was chosen because of its superior activityfor intestinal antisepsis. As a group they were not absorbed against Bacteroides fragilis and the base preparation wasfrom the gut and high intraluminal concentrations were selected because of poor absorption and high intraluminalachieved. Streptomycin was ﬁrst used in conjunction with concentrations, even though therapeutic systemic concen-sulfathalidine,19 but streptomycin was replaced with neo- trations of this preparation had been documented after oralmycin.20 Cohn21 subsequently popularized the use of kana- administration.26 The MBP was a 3-day regimen (Table 2).mycin as a single oral antibiotic preoperatively. The oral antibiotics (1 g of each drug) were given at 1:00 The litany of studies during the 1950s and 1960s were PM, 2:00 PM, and 11:00 PM the day before the surgery.based largely on microbiologic effects of the respective By using this mechanical and oral antibiotic regimen, adrugs, with no prospective and randomized clinical studies prospective and randomized clinical trial within the Veter-showing reduced rates of SSI. ans’ Administration followed this preliminary study by In the 1970s, a greater appreciation for the pathologic these same investigators. A placebo was compared withrole of anaerobic bacteria in infection emerged.22,23 Despite neomycin/erythromycin and showed a statistically signiﬁ-the recognition that anaerobes were in greatest concentra- cant reduction in SSIs (35% vs 9%) and in anastomotiction in the colon, they had largely been ignored in the leaks (10% vs 0%).27 Additional oral antibiotic studiesselection of oral antibiotics in colon surgery. In 1974, documented the value of metronidazole in place of eryth-Washington et al24 published the ﬁrst prospective random- romycin,28 and one study examined 3 oral drugs of neomy-ized trial of oral neomycin alone versus oral neomycin plus cin, phthalsulfathiazole, and tetracycline in the reduction oftetracycline versus a placebo in a 3-armed trial. In a unique SSIs.29 Further studies examined the merits of systemicclinical study, a single surgeon performed all the proce- antibiotics with the oral antibiotic bowel preparation anddures. A vigorous MBP was used with a low residue diet, showed reductions in SSI rates compared with using the oraloral sodium phosphate and biphosphate, and tap water en- bowel preparation only.30 –32 The rationale of both strategiesemas during 48 hours before the procedure (Table 2). The being used together was that oral antibiotics reduced theantibiotics or placebo were given over the same 48-hour inoculum of bacteria contaminating the surgical site fromperiod. Tetracycline was added because of its anaerobic the colon, and systemic antibiotics provided a safety net ofactivity, although it was absorbed to some degree and likely effective drug in the soft tissues to minimize the risk ofhad systemic effects, as was pointed out by Altemeier in the infection.