2. 226 The American Journal of Surgery, Vol 202, No 2, August 2011
Glenny8 similarly performed a large meta-analysis that Table 1 Provides the requirements of an ideal antibiotic
confirmed that preoperative administration of the drug is bowel preparation as defined by Poth
critical and that sustained administration of the antibiotic
for days after the procedure offers no benefit to the Low toxicity for the host
patient. The principals established in these studies have Broad antimicrobial spectrum
Chemical stability in the presence of digestive enzymes
been the basis for consensus performance measures that Capacity to prevent overgrowth or development of resistant
subsequently have been developed including those from bacteria
the Surgical Infection Prevention Project and its succes- Rapidity of action
sor 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 dehydration
sively moved toward a consensus opinion on the role of Nonirritant to enteric mucosa
systemic antibiotics, such has not been the case for the use Noninhibitor of healing
of colonic preparation. There continues to be confusion Low bacteriocidal dosage
about whether mechanical bowel preparation (MBP) alone Water soluble
is of any value in reducing SSI rates, and whether oral Palatable
Antifungal activity
antibiotics given in the preoperative period in conjunction Use restricted to intestinal antisepsis
with MBP is a useful technique in the prevention of infec-
tion. This presentation attempts to review the evolution of
the 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 reached
for 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 Preparation
beginning of resection as a treatment method for colonic
disease. Refinements in general anesthesiology and the Indeed, from the earliest time of the introduction of
advent 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 colon
cation. Colon resections from the era of the 1930s were because it was recognized that MBP did not reduce either
accompanied by mortality rates of 10% to 12% and had the concentration of bacteria or SSIs.13–15 The severity
SSI 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 being
that the human colon contained an unusually high con- marketed by companies, and the recognition from animal
centration of microbes. Cleansing the colon of gross fecal experiments that dramatic reductions in colonic bacteria
material was a logical strategy to reduce microbial con- density could be achieved with oral antibiotics led to
tamination 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 preparation
cleansing enhances the manipulation of the colon within for elective surgical intervention beginning in 1940. He
the 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 bacteria
operative MBP of the colon also was undertaken with the had to be diminished if any antimicrobial action was
assumption 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 any
through the subsequent decades, MBP became a part of retained fecal material often extended for several days
surgical lore even though no prospective randomized before the actual procedure. He formulated requirements
trials 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 drugs
surgery, Poth11 noted that although MBP reduced the bur- of choice because of poor absorption, high intraluminal
den of total bacteria in the colon, it did not reduce the concentrations, and effective reduction in aerobic bacte-
3. 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 PM
rial species within the colon.17,18 Although these sulfa discussion of the manuscript by Washington et al.24 The
preparations 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 al25
obligatory 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 of
quently 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 activity
for intestinal antisepsis. As a group they were not absorbed against Bacteroides fragilis and the base preparation was
from the gut and high intraluminal concentrations were selected because of poor absorption and high intraluminal
achieved. 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 oral
mycin.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, a
drugs, 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 with
role 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 anastomotic
tion in the colon, they had largely been ignored in the leaks (10% vs 0%).27 Additional oral antibiotic studies
selection 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 of
tetracycline versus a placebo in a 3-armed trial. In a unique SSIs.29 Further studies examined the merits of systemic
clinical study, a single surgeon performed all the proce- antibiotics with the oral antibiotic bowel preparation and
dures. A vigorous MBP was used with a low residue diet, showed reductions in SSI rates compared with using the oral
oral sodium phosphate and biphosphate, and tap water en- bowel preparation only.30 –32 The rationale of both strategies
emas during 48 hours before the procedure (Table 2). The being used together was that oral antibiotics reduced the
antibiotics or placebo were given over the same 48-hour inoculum of bacteria contaminating the surgical site from
period. Tetracycline was added because of its anaerobic the colon, and systemic antibiotics provided a safety net of
activity, although it was absorbed to some degree and likely effective drug in the soft tissues to minimize the risk of
had systemic effects, as was pointed out by Altemeier in the infection.