- Email: [email protected]
Preparation of the Bowel for Surgery
Symposium on Diseases of the Colon and Anorectum
Preparation of the Bowel for Surgery
Frederic P. Herter, M.D.*
The bacterial flora indigenous to the large bowel, important as it may be to the body's economy, continues to pose a serious threat in abdominal surgery. Despite long and widespread use of antibiotics in bowel preparation, as an adjunct to the surgical procedure itself and as a prophylactic function of the postoperative period, there is a substantial morbidity and mortality rate from sepsis following open procedures on the colon and rectum. In a coordinated study 18 emanating from five university hospitals in 1964, the overall wound infection incidence following bowel surgery was 12.9 per cent. Cohn 5 reported an infection rate of 13 per cent associated with 372 colon resections, Azar and Drapanos 2 a rate of 19 per cent in 445 elective colon operations, and in the Presbyterian Hospital a wound sepsis incidence of 20 per cent in 1042 consecutive ileocolectomies, colectomies and anterior resections. 12 A breakdown of colorectal operations performed at the Columbia-Presbyterian Medical Center in 1970, with infection rates, is seen in Table 1. Of 350 patients, 46 (13.1 per cent) developed local infection after surgery; anterior resection remained the most vulnerable category. These figures indicate some improvement over those of the previous survey, but they are still far too high to allow for complacency. Bacteriological studies of the 46 cases reported in 1970 indicate that enteric organisms are responsible for the vast majority of the infections (Table 2). It is difficult to escape the conclusion, therefore, that the significant incidence of septic complications reflects either poor bowel preparation (mechanical, antibiotic, or both), carelessness in surgical technique, the injudicious use of systemic antibiotics, or a combination of these factors. It is not within the province of this paper to discuss operative methodology, or to weigh the pros and cons of so-called prophylactic antimicrobial therapy. Of all the factors bearing on infection control, however, proper surgical technique is certainly the most important. *Professor of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York.
Surgical Clinics of North America- Vol. 52, No.4, August 1972
859
860
FREDERIC
P.
HERTER
Table 1. Wound Infections Following Colorectal Operations. Columbia-Presbyterian Medical Center, 1970 WOUND INFECTIONS*
OPERATIONS
No. Major
No. Minor
Total
Per Cent
19 54 89 28 111 49 350
2 2 8 5 7 5 29
2 8 2 4 0 17
3 4 16 7 11 5 46
15.8 7.4 17.9 25.0 10.0 10.2 13.1
NO. OF OPERATION
Abdominoperineal resection Ileocolectomy Colectomy with anastomosis Anterior resection Colostomy (revision, closure), cecostomy Trans. abdominal polypectomy Total
*Septicemia without overt wound infection occurred in 1 abdominoperineal resection (Klebsiella), 2 ileocolectomies (Klebsiella, E. coli-fatal), and 3 colectomies (Bacteroides, Enterobacter, Pseudomonas-fatal).
Table 2. Organisms in 46 Wound Infections. Columbia-Presbyterian Medical Center, 1970
ORGANISM*
E. coli Bacteroides Klebsiella Proteus Enterobacter Pseudomonas Streptococcus viridans Staphylococcus (coagulation-positive) Streptococcus (beta-hemolytic) Streptococcus (non-hemolytic)
NO.
PER CENT
WOUNDS
WOUNDS
31 26 13 11 11 7 6 4 2 2
67 57 28 24 24 15 13 9 5 5
*Five organisms were cultured from 3 wounds, four from 7, three from 12, two from 11 and one from 13 wounds.
PREPARATION OF THE BOWEL FOR SURGERY
861
MECHANICAL PREPARATION There can be little disagreement with the premise that mechanical cleansing is the keystone to effective bowel preparation for surgery. Without significant reduction in the stool mass, intestinal antibiotics are worthless preoperatively, and the degree of contamination at surgery, regardless of technique, will frequently render the normal peritoneal defenses useless. It is also obvious that the type and degree of mechanical preparation must be tailored to the patient in question. Rigorous purging, repeated enemata, and systematic diet reduction are poorly tolerated by the fragile and the elderly; electrolyte (particularly potassium) and water depletion can occur, potentially compromising the safety of anesthesia induction and the ensuing major surgery, and occasionally necessitating parenteral restoration of losses preoperatively. Moreover, the patient withpartial obstruction may require a more protracted period of diet limitation than the one without obstruction, as well as more vigorous purging and enema cleansing. It is therefore imperative that the general state of the patient be carefully assessed prior to initiation of preparation, as well as the degree of mechanical large bowel obstruction present, and modifications in routine applied accordingly. All colon cases fall into one of three general categories with respect to obstruction, and in each the preparation differs: 1. Total or near-total obstruction. Such patients present with obstipation or progressively severe constipation, abdominal distention and discomfort (with or without cramps), obstruction to the retrograde flow of barium, and x-ray evidence of a markedly dilated, stool-filled right colon. Mechanical measures to evacuate the bowel in these circumstances are not only worthless, but dangerous. Proximal decompression in the form of cecostomy or transverse colostomy must be carried out as a preliminary procedure, followed by 10 to 14 days of intense mechanical cleansing (proximal and distal loops if transverse colostomy has been done) prior to definitive resective surgery. 2. Partial obstruction. A change in bowel habits is usually present in the form of progressive constipation, diarrhea, or alternating constipation and diarrhea. Abdominal distention is absent, and x-rays reveal partial and variable obstruction to retrograde barium flow, with a stool-filled but not significantly dilated right colon. Mechanical preparation may or may not be effective in such patients. A low residue diet should be instituted when the diagnosis is first made, and the results from tentative mild purgation assessed. If stimulation of the bowel induces crampy pain, without corresponding evacuation, or if trial enemas produce few or no returns, consideration should be given to proximal diversion as a prelude to resection. If, on the other hand, these mild trial measures are effective and tolerated by the patient, nonoperative preparation can continue. The low residue diet should be replaced by a full fluid diet 4 to 5 days before the scheduled operation; in other respects, preparation should be that outlined below. A flat plate of the abdomen should be obtained the day before surgery; evidence of stool retention in the right colon should force a deferment of surgery for an additional day or two of preparation.
862
FREDERIC
P.
HERTER
For the management of the patient with partial obstruction, many surgeons find virtue in adding a bacteriostatic intestinal antibiotic, such as phthalylsulfathiazole (Sulfathalidine), during the last 5 to 7 days of diet reduction and mechanical cleansing, to further reduce stool bulk. 3. No obstruction. These patients are generally asymptomatic, and x-rays reveal an unobstructive bowel pattern. Mechanical preparation should be highly effective in this category. Many variations are possible within the basic triad of diet reduction, purgation, and enemata (in this Department there are as many different routines as there are abdominal surgeons), but my own preference is for the following: 3 days before operation:
Low residue diet. A.M.-Phosphosoda, 45 cc, or Neoloid, 60 cc. P.M.-SSE 2 days before operation: Full fluid diet (soups, juices, soft boiled egg, farina, jello, junket) A.M.-Phosphosoda, 45 cc, or Neoloid, 60 cc. (This should be optional, depending on the status of the patient, and the results of the previous day.) P.M.-SSE 1 day before operation: Clear fluid diet (water, tea, broth, ginger ale) P.M.- Saline enemas until returns are clear. Day of operation: Nothing by mouth as of midnight. No rectal treatments.
It should be re-emphasized that a regimen such as this can result in consequential depletion of water and electrolyte reserves. Should there be clinical evidence of dehydration on the day prior to surgery, serum electrolyte and hematocrit determinations should be obtained, followed by appropriate parenteral replacement. On the day of surgery, an infusion should be started and continued throughout the morning if the procedure is not scheduled until the afternoon. Careful attention to the needs for rehydration preoperatively should obviate the frequently observed hypotension attendant on induction of anesthesia in such patients.
ANTIBIOTIC PREPARATION Impossible as it is to sterilize completely the large intestine with antibiotics, relative sterility can be achieved by this means, provided that stool bulk is effectively reduced mechanically. On theoretical grounds, this should be a laudable goal for every abdominal surgeon concerned about infection. Yet, ever since the introduction by Garlock and Seley 9 in 1939 of the sulfonamides for bowel preparation and the later addition of the nonabsorbable broad-spectrum agents, controversy has raged over the efficacy and possible dangers of intestinal antibiotics; even today there are widely divergent opinions (even within the same institutions) as to the indications for their use. The basis for controversy revolves about two questions: "superinfection," and the relationship between bacterial sterility and suture line re-
PREPARATION OF THE BOWEL FOR SURGERY
863
currence of tumor. Beginning in the mid 1950's and continuing for about 10 years, the surgical literature was flooded with reports of pseudomembranous or staphylococcal enterocolitis occurring as a function of intestinal antimicrobial therapy. This entity had of course been described earlier, even in the pre-antibiotic days and in nonsurgical situations, but the epidemic proportions of its occurrence during that decade appeared to be related to the widespread, almost universal, use of broad-spectrum antibiotics in preparing the bowel for surgery. It was postulated that suppression of certain enteric bacterial populations by antibiotics permitted the unrivaled emergence of other organisms of pathogenic nature, principally hemolytic Staphylococcus aureus. Despite the fact that no dominant organism could be isolated from some cases of pseudomembranous enterocolitis, the staphylococcus was incriminated in most instances of both the membranous and nonmembranous forms of the disease. Hummel and Altemeier14 studied a group of patients who had been prepared for surgery with neomycin; in 4 of 30, S. aureus was cultured from the stool prior to antibiotic therapy, whereas in 23, stool cultures were posi-. tive for S. aureus after therapy. In 22 of these 23 patients, the staphylococcus was phage-typed as UC-18. Eight patients had postoperative diarrhea; S. aureus (UC-18) was isolated from all 8. One died from enterocolitis. Moreover, of 5 patients with wound infections, 4 had cultures positive for S. aureus, three of the UC-18 type. In a later study, Altemeier1 compared various regimens of preoperative and postoperative antibiotics in 93 patients; the combination of neomycin and phthalylsulfathiazole (Sulfathalidine) preoperatively with penicillin and tetracyline postoperatively produced the highest incidence of diarrhea (21 per cent). Azar and Drapanos 2 reported a 10 per cent incidence of enterocolitis following 445 elective colon resections; the greatest predisposition to this complication occurred in those patients prepared for surgery with intestinal antibiotics and treated prophylactically with antibiotics in the postoperative period. In the same series, staphylococci were cultured from 44 per cent of the postoperative wound infections, although the organism was isolated by culture from only one individual at the time of operation. Vandertoll and Beahrs 19 stressed the seriousness of enterocolitis as a complication in reporting the results of 1766 curative anterior resections performed between 1946 and 1957; of the 74 operative (hospital) deaths, 14, or 18.9 per cent, resulted from enterocolitis. The responsible organisms were not described. Polacek and Sanfelippo 15 reported a 27 per cent incidence of diarrhea, and a 23 per cent rate of wound infection, in a sizeable number of patients undergoing open colon anastomoses and prepared with intestinal antibiotics. The control group, prepared for surgery with mechanical measures only, but treated prophylactically with systemic antibiotics postoperatively, fared significantly betterthere was no diarrhea, and a 4 per cent wound infection rate. In our own retrospective study of infection following 1042 colonic resections (12), enterocolitis developed in less than 1 per cent; in eight of the ten cases, antibiotics had been employed in intestinal preparation. There were two deaths, and staphylococci were cultured from the stool in
864
FREDERIC
P.
HERTER
both. Welch and Burke 21 reported three deaths from staphylococcal enterocolitis in over 1300 colorectal operations, an incidence similar to our own. Moving further to the other end of the spectrum, Cohn 5 claimed only one instance of enterocolitis in over 800 patients prepared with kanamycin or a combination of neomycin and tetracyline, and Poth,t 7 who has championed the use of neomycin plus phthalylsulfathiazole (Sulfathalidine) in bowel preparation, denied the occurrence of a single case of pseudomembranous enterocolitis between 1950 and 1964. The discrepancy in the rate of occurrence of this form of "superinfection" between various reporting institutions is of considerable interest. Of greater interest, and probable pertinence, is the fact that staphylococcal enterocolitis, as an entity, has disappeared from· the literature during the past 5 years and has not been a topic of discussion in surgical meetings. During this period, we have not had a single case among our adult population, and I gather that the same phenomenon has obtained at other hospitals. This is not a reflection of any change in our routine of bowel preparation, and we must assume that the particular strain of S. aureus responsible for the almost epidemic appearance of enterocolitis during that earlier decade has indeed disappeared. Support for this assumption comes from the fact that other bacterial strains have similarly made dramatic entries and exits in wound infection studies. Dr. C. W. Findlay, Director of the Meleney Surgical Bacteriology Laboratory at Columbia, informs me that in 1967, Klebsiella occurred in a disproportionately high percentage of our wound infections, as well as a strain of methicillin-resistant staphylococcus. 8 At present, the incidence of infection from bacteroides is on the ascendency, as can be seen in Table 2. It would appear likely that periodic variations in the occurrence and pathogenicity of certain organisms may be anticipated, depending to a degree on antibiotic usage but also on other poorly defined influences beyond our present control. Regardless of the divergent observations and views cited above, there is little question but that an imbalance in the bacterial population of the large bowel, induced by antibiotic therapy, can occasionally lead to a clinically serious emergence of an opportunistic organism. Moreover, the arbitrary use of systemic antibiotics may, in some ill-defined manner, render the host more susceptible to resistant organisms. This matter has been studied experimentally. Dubos and Schaedler/ working with a group of mice free of the normal enteric bacterial pathogens, but not absolutely germ free, found that the protected animals grew more quickly, continued to grow on diets that were deficient to control mice, but were more susceptible than controls to experimental bacterial infections (staphylococcus, Klebsiella, tuberculosis, etc.). Dineen,6 in 1960, pursued these observations further; using a 0.1 per cent concentration of neomycin in the diet, thus lowering the microbial census in the gut, he then challenged mice with an intravenous inocculation of hemolytic S. aureus. The SD-50 for the control animals was 14 days, and for the neomycin-prepared mice 5 days. In addition, the staphylococcus count in the kidneys of the sacrificed neomycin treated animals was significantly higher than in the controls.
865
PREPARATION OF THE BOWEL FOR SURGERY
Table 3.
Prophylactic Antibiotics used in Five University Hospitals, 1964 INFECTION RATE, PER CENT
CLASS OF WOUND
Proph. Antibiotics (4,642 Wounds)
No Antibiotics (10,502 Wounds)
Refined- clean Other Clean Clean- contaminated Contaminated Dirty Inclusive
9.4 11.7 13.9 20.4 31.7 14.3
2.3 5.4 6.8 10.6 22.2 4.4
Supportive of these experimental observations was the clinical study of surgical infection carried out by five university hospitals, mentioned earlier. 18 Patients receiving prophylactic antibiotics had a significantly higher wound infection rate than those untreated by antibiotics, as seen in Table 3. Even adjusting for the large proportion of non-clean wounds in the antibiotic group, there was a disparity in results; the infection rate was 12.2 per cent in the group receiving antibiotics, and 5.2 per cent in the controls. Here again, then, we find suggestive information relating antibiotics to host resistance, although the mechanisms involved are unclear. The second area of contention with respect to antibiotic bowel antisepsis involves the entity of suture-line recurrence. In 1954, Vink 20 published the results of an experimental study in rabbits in which the implantation and growth of inocculated viable tumor cells at the anastomotic line, following colon resection, appeared to be favored by relative bacterial sterility. This study was refined and amplified by Cohn 3 in 1960, with essentially the same findings, namely, that antibiotic control of the intestinal flora increased the possibilities of implantation tumor growth. Although the results of our own attempts to duplicate Vink's work were equivocal, 11 a subsequent clinical study 13 from this institution lent suggestive corroboration to Vink's thesis. Twenty-five documented suture line recurrences were observed following 790 colon resections, an overall incidence of 3.2 per cent. Of particular pertinence was the observation that 15 of the 16 recurrences after anterior resection occurred in patients prepared for surgery with intestinal antibiotics. It thus appears that intestinal antibiotics do carry some degree of threat, both theoretical and actual, with respect to this form of tumor spread, and that this threat must be countered by assiduously applied measures to rid the bowel of viable desquamated tumor cells prior to anastomosis. Ligation of the bowel above and below the tumor prior to its manipulation, irrigation of the divided ends of the bowel with cancericidal agents, and the use of iodized catgut in the anastomosis, all represent suggested methods of avoiding implantation recurrence. In most institutions today, they have become part of the technical ritual of colon resection for cancer.
866
FREDERIC
P.
HERTER
CRITERIA FOR THE USE OF ANTIBIOTICS The foregoing has dealt with the theoretical disadvantages of intestinal antibiotics. Are there compensating advantages, and if so, under what circumstances? Cohn 5 presents a convincing argument for their use-in over 1000 patients prepared for colon surgery with either kanamycin or neomycin and tetracyline, he has encountered no reportable toxicity, a negligible incidence of enterocolitis, and an overall wound infection rate of 10 per cent (13. 7 per cent for colon resections). Unfortunately, he does not have a control group of patients with whom to co:.:npare results. Poth is equally vehement in his defenses of antibiotic preparation. His comparative clinical study in 1960 15 of 170 patients undergoing bowel surgery after a variety of preparatory regimens certainly substantiates his enthusiasm; 18 patients prepared by mechanical measures only, and given antibiotics postoperatively, had an 11 per cent mortality and a 77.7 per cent wound infection rate. In contrast, of 58 patients prepared with neomycin-phthalylsulfathiazole (Sulfathalidine), only 3.4 per cent developed wound infections. When 0.5 per cent neomycin irrigation of the wound at surgery was added to the same preoperative preparation in an additional 59 patients, the wound infection rate was an astounding 1. 7 per cent. Four years later, in a discussion of a paper by Hummel and Altemeier/7 Poth stated that in over 250 open anastomoses performed from 1941 on in patients prepared with antibiotics, he had not a single anastomotic leak, not a single localized abscess, not a single instance of peritonitis, and no operative deaths! No others have come close to duplicating these figures, but additional published reports are supportive. Azar and Drapanos 2 cite a 17.9 per cent wound infection rate in 414 patients prepared with neomycin-phthalylsulfathiazole (Sulfathalidine), as opposed to a 36 per cent infection rate in 31 patients treated with postoperative antibiotics only. Hafner 10 reports a 13.5 per cent infections complication incidence following 200 consecutive colon resections prepared with a variety of chemical agents. The control group is small; 8 of 13 patients, however, prepared by mechanical cleansing only, developed wound infections. A sizeable retrospective study from this institution, 12 designed to better define the influence of chemical bowel preparation, compared 724 patients undergoing colon resection after antibiotic preparation with 318 patients prepared by mechanical measures only. The wound infection rate was 18.2 per cent in the former group, and 24.9 per cent in the controls. The difference was not statistically significant for intraperitoneal anastomoses, however. Only in the anterior resection category did antibiotic preparation appear to hold a substantial advantage; an anastomotic leak rate of 8 per cent contrasted sharply with the 25 per cent rate encountered in unprepared patients, and the overall wound infection rate following anterior resection was 24 per cent for prepared patients and 43 per cent for those unprepared. It was our conclusion that antibiotic preparation should be reserved only for those patients undergoing a resection involving an extraperitoneal anastomosis.
PREPARATION OF THE BOWEL FOR SURGERY
867
Despite the admitted limitations of retrospective clinical investigations, we have not felt compelled to alter the conclusions of that study during the past 4 years. Persuasive though the arguments may appear to be for blanket coverage of all colon operations with preoperative antibiotics, we remain impressed by the subtle though nonetheless real dangers of creating an imbalance in the intestinal flora by such treatment. Additionally, it is our opinion that good mechanical preparation, plus careful surgical technique, are factors of greater importance than chemical antimicrobial therapy in infection control. As such the following indications for antibiotic usage are suggested: 1. Antibiotic bowel preparation should be employed
a. For colon resections entailing an extraperitoneal anastomosis. b. For resective bowel surgery where there is partial obstruction and the possibility of imperfect mechanical preparation. 2. Antibiotic bowel preparation should be omitted in elective intraperitoneal resections for nonobstructing tumors, providing mechanical cleansing is satisfactory. 3. Irrigation of the operative field and wound with a topical antibiotic agent (kanamycin or neomycin-bacitracin) is advisable. 4. Routine prophylactic postoperative antibiotic therapy should be avoided.
CHOICE OF ANTIBIOTICS The most comprehensive study of the effects of antibiotics on the intestinal flora has been carried out by Cohn. 5 Under strict protocol, 48 different agents or drug combinations were investigated with respect to their ability to rid the bowel of streptococci, staphylococci, coliforms, clostridia, and bacteroides. The poorly absorbed sulfa preparations, such as succinylsulfathiazole (Sulfasuxidine) and phthalylsulfathiazole (Sulfathalidine), were found to be inadequate when used alone, as were the various tetracyclines and penicillins. Cohn concluded that the most effective single drug was kanamycin, this based on its lack of toxicity and its activity against all enteric organisms except bacteroides. Neomycin alone was found to be less adequate as an antibacterial, and more toxic; the addition of one of a number of agents (amphotericin, bacitracin, nystatin, polymyxin-B, phthalylsulfathiazole, Thiostrepton) to neomycin, however, produced a highly satisfactory antibiotic combination. Poth 16 has been the principal advocate of the neomycin-phthalylsulfathiazole combination, and his views have received widespread support. No other antibiotic regimen has been employed with greater frequency. Our laboratory of Surgical Bacteriology has found neomycin to have the same spectrum of antibacterial activity as kanamycin; moreover, the nausea, vomiting, and diarrhea cited by Cohn as toxic manifestations of neomycin administration have been virtually absent in our experience. It has been used as the single agent of choice in this institution for several years, not because of its documented superiority over kanamycin, but because of familiarity with use and demonstrated effectiveness. A combination of neomycin and bacitracin had previously been employed routinely in bowel preparation (in no small part because bacitracin had been
868
FREDERIC
P.
HERTER
developed at this institution), but there are no hard statistical data from our laboratory to indicate that this combination was more advantageous than neomycin alone. Cohn's studies suggest that bacteroides are better controlled by neomycin-bacitracin than by neomycin alone, and in view of the recent upsurge in serious bacteroides infections at this hospital, we probably would be well advised to reconsider the use of the combination again. Although phthalylsulfathiazole (Sulfathalidine) alone appears to have little activity against bacteroides, its combination with neomycin appears to be highly effective in Cohn's hands in suppressing this class of organisms well beyond the treatment period. Given the current increase in bacteroides wound infections, then, we would favor either of the above combinations over kanamycin or neomycin alone. Although Poth has advocated a 24 hour period of antibiotic bowel preparation only, theoretically based on the possible emergence of resistent strains with longer treatment, Cohn's observations suggest that complete bacterial control is not effected in such a short period. He advises treatment of 72 hours' duration. My personal preference, which I confess has a largely empirical basis, strikes a compromise between the two-namely, 36 hours. Antibiotic therapy is begun on the afternoon of the second day before surgery, accordingly to the following schedule: Second preoperative day: Neomycin, 1 gm. plus bacitracin, 40,000 units or Sulfathalidine, 1.5 gm., at 1, 2, 3, 4, and 10 o'clock in the P.M. First preoperative day: Neomycin, 1 gm., plus bacitracin, 40,000 units of sulfathalidine, 1.5 gm., at 4 and 10 o'clock in the A.M., and 4 and 10 o'clock in the P.M.
DISCUSSION The principal reason that controversy continues to exist in this important area of surgery is that no large scale randomized, prospective clinical study, comparing antibiotic preparation of the bowel with mechanical preparation alone, has ever been completed. Such a study should be carried out in a single institution, and involve the same group of surgeons operating with highly standardized surgical techniques. The case sampling must be large enough to allow for comparable pathologic and clinical material; mechanical measures to cleanse the bowel should be applied consistently, and insofar as possible, with uniformity; and bacteriologic data should be collected and analyzed under strict protocol. This type of undertaking is at best difficult and time-consuming, considering the number of variables, but it must be done if empiricism and emotionalism are to be eliminated from our thinking. Cohn has introduced order into the evaluation of the various antibiotic agents available for intestinal preparation; what he has not answered, however, is the basic question as to whether intestinal antibiotics add measurable protection from infection over and above that provided by mechanical preparation alone plus careful surgical technique. Nor have the innumerable other contributors to this literature-there are almost as many de-
PREPARATION OF THE BOWEL FOR SURGERY
869
tractors as there are antibiotic supporters. Our efforts to arrive at conclusions through retrospective analyses have been somewhat less than satisfactory, as might have been anticipated. The variables are too great to reconcile retrospectively, and the lack of randomization of case material permits inevitable bias in choice of management to enter in. Thus certain conclusions or impressions arrived at herein with respect to the use of antibiotics admittedly emanate from an insecure data base and must be considered tentative, pending the prospective investigation outlined above.
SUMMARY AND CONCLUSIONS Wound infection rates following open operations on the colon and rectum remain high, and call for a reevaluation of methods of bowel preparation. Mechanical preparation, through diet reduction, purgation, and enemata, is of paramount importance, whether or not antibiotics are em-ployed. A regimen for mechanical cleansing of the bowel is suggested. Arguments for and against the use of intestinal antibiotics are presented, relating particularly to "superinfection," suture line recurrence, and possible changes in host resistance to infection. Antibiotic preparation is advocated in the presence of partial bowel obstruction, where mechanical measures may be unsatisfactory, and for resections in which an extraperitoneal anastomosis is anticipated. Both kanamycin and neomycin, the two single most effective agents against enteric pathogens, fail to control bacteroides, the source of many recent wound infections, and the addition of bacitracin or Sulfathalidine is recommended.
REFERENCES 1. Altemeier, W. A., Hummel, R. P., and Hill, E. 0. Prevention of infection in colon surgery. Arch. Surg., 93:226, 1966. 2. Azar, H., and Drapanos, T.: Relationship of antibiotics to wound infection and enterocolitis in colon surgery. Amer. J. Surg., 115:209, 1968. 3. Cohn, I., Jr., and Atik, M.: The influence of antibiotics on the spread of tumors of the colon. Ann. Surg., 151 :917, 1960. 4. Cohn, I., Jr.: Discussion of paper by Hummel, R. P., Altemeier, W. A., and Hill,'E. 0., Ann. Surg., 160:551, 1964. 5. Cohn, I., Jr.: Intestinal Antisepsis. Springfield, Illinois, Charles C Thomas, 1968. 6. Dineen, P.: Effect of reduction of bowel flora on experimental staphylococcal infection in mice. Proc. Soc. Exper. Biol. Med., 104:760, 1960. 7. Bubos, R. S., and Schaedler, R. W.: The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections. J. Exper. Med., 110:935, 1959. 8. Findlay, C. W., Jr.: Personal communication, 1971. 9. Garlock, J. H., and Seley, G. P.: The use of sulfanilamide in surgery of the colon and rectum. Preliminary report. Surgery, 5:787, 1939. 10. Hafner, C. D.: Antibiotics in colon surgery. Amer. J. Surg., 121:673, 1971. 11. Herter, F. P., Santulli, T.V., Terry, S., Buda, J. A., and Beals, R. L.: An experimental study of the influence of the intestinal bacterial flora on suture line recurrence following resection for carcinoma of the colon. Surg. Gynec. Obstet., 114:267, 1962.
870
FREDERIC
P.
HERTER
12. Herter, F. P., and Slanetz, C. A., Jr.: Influence of antibiotic preparation of the bowel on complications after colonic resection. Amer. J. Surg., 113:165, 1966. 13. Herter, F. P., and Slanetz, C., Jr.: Preoperative intestinal preparation in relation to the subsequent development of cancer at the suture line. Surg. Gynec. Obstet., 127:49, 1968. 14. Hummel, R. P., Altemeier, W. A., and Hill, E. 0.: Iatrogenic staphylococcal enterocolitis. Ann. Surg., 160:551, 1964. 15. Polacek, M.A., and San Felippo, P.: Oral antibiotic bowel preparation and complications in colon surgery. Arch. Surg., 97:412, 1968. 16. Poth, E. J.: The role of intestinal antisepsis in the preparative preparations of the colon. Surgery, 47:1018, 1960. 17. Poth, E. A.: Discussion of paper by Hummel, R. P., Altemeier, W. A., and Hill, E. 0.: Ann. Surg., 160:551, 1964. 18. Report of an Ad Hoc Committee of the Committee on Trauma, Division of Medical Sciences, National Research Council, National Academy of Sciences: The influence of ultaviolet irradiation of the operating room and various other factors. Ann. Surg., 160(Suppl.):1-192, 1964. 19. Vandertoll, D. J., and Beahrs, 0. H.: Carcinoma of the rectum and low sigmoid; evaluation of anterior resection of 1766 favorable lesions. Arch. Sug., 90:193, 1965. 20. Vink, M.: Local recurrence of cancer in the large bowel; the role of implantation metastases and bowel disinfection. Brit. J. Surg., 41:431, 1954. 21. Welch, C. E., and Burke, J. F.: Carcinoma of the colon and rectum. New Eng. J. Med., 266:2.11-219, 1962. Department of Surgery Columbia University College of Physicians and Surgeons 630 West 168th Street New York, New York
Preparation of the Bowel for Surgery
Frederic P. Herter, M.D.*
The bacterial flora indigenous to the large bowel, important as it may be to the body's economy, continues to pose a serious threat in abdominal surgery. Despite long and widespread use of antibiotics in bowel preparation, as an adjunct to the surgical procedure itself and as a prophylactic function of the postoperative period, there is a substantial morbidity and mortality rate from sepsis following open procedures on the colon and rectum. In a coordinated study 18 emanating from five university hospitals in 1964, the overall wound infection incidence following bowel surgery was 12.9 per cent. Cohn 5 reported an infection rate of 13 per cent associated with 372 colon resections, Azar and Drapanos 2 a rate of 19 per cent in 445 elective colon operations, and in the Presbyterian Hospital a wound sepsis incidence of 20 per cent in 1042 consecutive ileocolectomies, colectomies and anterior resections. 12 A breakdown of colorectal operations performed at the Columbia-Presbyterian Medical Center in 1970, with infection rates, is seen in Table 1. Of 350 patients, 46 (13.1 per cent) developed local infection after surgery; anterior resection remained the most vulnerable category. These figures indicate some improvement over those of the previous survey, but they are still far too high to allow for complacency. Bacteriological studies of the 46 cases reported in 1970 indicate that enteric organisms are responsible for the vast majority of the infections (Table 2). It is difficult to escape the conclusion, therefore, that the significant incidence of septic complications reflects either poor bowel preparation (mechanical, antibiotic, or both), carelessness in surgical technique, the injudicious use of systemic antibiotics, or a combination of these factors. It is not within the province of this paper to discuss operative methodology, or to weigh the pros and cons of so-called prophylactic antimicrobial therapy. Of all the factors bearing on infection control, however, proper surgical technique is certainly the most important. *Professor of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York.
Surgical Clinics of North America- Vol. 52, No.4, August 1972
859
860
FREDERIC
P.
HERTER
Table 1. Wound Infections Following Colorectal Operations. Columbia-Presbyterian Medical Center, 1970 WOUND INFECTIONS*
OPERATIONS
No. Major
No. Minor
Total
Per Cent
19 54 89 28 111 49 350
2 2 8 5 7 5 29
2 8 2 4 0 17
3 4 16 7 11 5 46
15.8 7.4 17.9 25.0 10.0 10.2 13.1
NO. OF OPERATION
Abdominoperineal resection Ileocolectomy Colectomy with anastomosis Anterior resection Colostomy (revision, closure), cecostomy Trans. abdominal polypectomy Total
*Septicemia without overt wound infection occurred in 1 abdominoperineal resection (Klebsiella), 2 ileocolectomies (Klebsiella, E. coli-fatal), and 3 colectomies (Bacteroides, Enterobacter, Pseudomonas-fatal).
Table 2. Organisms in 46 Wound Infections. Columbia-Presbyterian Medical Center, 1970
ORGANISM*
E. coli Bacteroides Klebsiella Proteus Enterobacter Pseudomonas Streptococcus viridans Staphylococcus (coagulation-positive) Streptococcus (beta-hemolytic) Streptococcus (non-hemolytic)
NO.
PER CENT
WOUNDS
WOUNDS
31 26 13 11 11 7 6 4 2 2
67 57 28 24 24 15 13 9 5 5
*Five organisms were cultured from 3 wounds, four from 7, three from 12, two from 11 and one from 13 wounds.
PREPARATION OF THE BOWEL FOR SURGERY
861
MECHANICAL PREPARATION There can be little disagreement with the premise that mechanical cleansing is the keystone to effective bowel preparation for surgery. Without significant reduction in the stool mass, intestinal antibiotics are worthless preoperatively, and the degree of contamination at surgery, regardless of technique, will frequently render the normal peritoneal defenses useless. It is also obvious that the type and degree of mechanical preparation must be tailored to the patient in question. Rigorous purging, repeated enemata, and systematic diet reduction are poorly tolerated by the fragile and the elderly; electrolyte (particularly potassium) and water depletion can occur, potentially compromising the safety of anesthesia induction and the ensuing major surgery, and occasionally necessitating parenteral restoration of losses preoperatively. Moreover, the patient withpartial obstruction may require a more protracted period of diet limitation than the one without obstruction, as well as more vigorous purging and enema cleansing. It is therefore imperative that the general state of the patient be carefully assessed prior to initiation of preparation, as well as the degree of mechanical large bowel obstruction present, and modifications in routine applied accordingly. All colon cases fall into one of three general categories with respect to obstruction, and in each the preparation differs: 1. Total or near-total obstruction. Such patients present with obstipation or progressively severe constipation, abdominal distention and discomfort (with or without cramps), obstruction to the retrograde flow of barium, and x-ray evidence of a markedly dilated, stool-filled right colon. Mechanical measures to evacuate the bowel in these circumstances are not only worthless, but dangerous. Proximal decompression in the form of cecostomy or transverse colostomy must be carried out as a preliminary procedure, followed by 10 to 14 days of intense mechanical cleansing (proximal and distal loops if transverse colostomy has been done) prior to definitive resective surgery. 2. Partial obstruction. A change in bowel habits is usually present in the form of progressive constipation, diarrhea, or alternating constipation and diarrhea. Abdominal distention is absent, and x-rays reveal partial and variable obstruction to retrograde barium flow, with a stool-filled but not significantly dilated right colon. Mechanical preparation may or may not be effective in such patients. A low residue diet should be instituted when the diagnosis is first made, and the results from tentative mild purgation assessed. If stimulation of the bowel induces crampy pain, without corresponding evacuation, or if trial enemas produce few or no returns, consideration should be given to proximal diversion as a prelude to resection. If, on the other hand, these mild trial measures are effective and tolerated by the patient, nonoperative preparation can continue. The low residue diet should be replaced by a full fluid diet 4 to 5 days before the scheduled operation; in other respects, preparation should be that outlined below. A flat plate of the abdomen should be obtained the day before surgery; evidence of stool retention in the right colon should force a deferment of surgery for an additional day or two of preparation.
862
FREDERIC
P.
HERTER
For the management of the patient with partial obstruction, many surgeons find virtue in adding a bacteriostatic intestinal antibiotic, such as phthalylsulfathiazole (Sulfathalidine), during the last 5 to 7 days of diet reduction and mechanical cleansing, to further reduce stool bulk. 3. No obstruction. These patients are generally asymptomatic, and x-rays reveal an unobstructive bowel pattern. Mechanical preparation should be highly effective in this category. Many variations are possible within the basic triad of diet reduction, purgation, and enemata (in this Department there are as many different routines as there are abdominal surgeons), but my own preference is for the following: 3 days before operation:
Low residue diet. A.M.-Phosphosoda, 45 cc, or Neoloid, 60 cc. P.M.-SSE 2 days before operation: Full fluid diet (soups, juices, soft boiled egg, farina, jello, junket) A.M.-Phosphosoda, 45 cc, or Neoloid, 60 cc. (This should be optional, depending on the status of the patient, and the results of the previous day.) P.M.-SSE 1 day before operation: Clear fluid diet (water, tea, broth, ginger ale) P.M.- Saline enemas until returns are clear. Day of operation: Nothing by mouth as of midnight. No rectal treatments.
It should be re-emphasized that a regimen such as this can result in consequential depletion of water and electrolyte reserves. Should there be clinical evidence of dehydration on the day prior to surgery, serum electrolyte and hematocrit determinations should be obtained, followed by appropriate parenteral replacement. On the day of surgery, an infusion should be started and continued throughout the morning if the procedure is not scheduled until the afternoon. Careful attention to the needs for rehydration preoperatively should obviate the frequently observed hypotension attendant on induction of anesthesia in such patients.
ANTIBIOTIC PREPARATION Impossible as it is to sterilize completely the large intestine with antibiotics, relative sterility can be achieved by this means, provided that stool bulk is effectively reduced mechanically. On theoretical grounds, this should be a laudable goal for every abdominal surgeon concerned about infection. Yet, ever since the introduction by Garlock and Seley 9 in 1939 of the sulfonamides for bowel preparation and the later addition of the nonabsorbable broad-spectrum agents, controversy has raged over the efficacy and possible dangers of intestinal antibiotics; even today there are widely divergent opinions (even within the same institutions) as to the indications for their use. The basis for controversy revolves about two questions: "superinfection," and the relationship between bacterial sterility and suture line re-
PREPARATION OF THE BOWEL FOR SURGERY
863
currence of tumor. Beginning in the mid 1950's and continuing for about 10 years, the surgical literature was flooded with reports of pseudomembranous or staphylococcal enterocolitis occurring as a function of intestinal antimicrobial therapy. This entity had of course been described earlier, even in the pre-antibiotic days and in nonsurgical situations, but the epidemic proportions of its occurrence during that decade appeared to be related to the widespread, almost universal, use of broad-spectrum antibiotics in preparing the bowel for surgery. It was postulated that suppression of certain enteric bacterial populations by antibiotics permitted the unrivaled emergence of other organisms of pathogenic nature, principally hemolytic Staphylococcus aureus. Despite the fact that no dominant organism could be isolated from some cases of pseudomembranous enterocolitis, the staphylococcus was incriminated in most instances of both the membranous and nonmembranous forms of the disease. Hummel and Altemeier14 studied a group of patients who had been prepared for surgery with neomycin; in 4 of 30, S. aureus was cultured from the stool prior to antibiotic therapy, whereas in 23, stool cultures were posi-. tive for S. aureus after therapy. In 22 of these 23 patients, the staphylococcus was phage-typed as UC-18. Eight patients had postoperative diarrhea; S. aureus (UC-18) was isolated from all 8. One died from enterocolitis. Moreover, of 5 patients with wound infections, 4 had cultures positive for S. aureus, three of the UC-18 type. In a later study, Altemeier1 compared various regimens of preoperative and postoperative antibiotics in 93 patients; the combination of neomycin and phthalylsulfathiazole (Sulfathalidine) preoperatively with penicillin and tetracyline postoperatively produced the highest incidence of diarrhea (21 per cent). Azar and Drapanos 2 reported a 10 per cent incidence of enterocolitis following 445 elective colon resections; the greatest predisposition to this complication occurred in those patients prepared for surgery with intestinal antibiotics and treated prophylactically with antibiotics in the postoperative period. In the same series, staphylococci were cultured from 44 per cent of the postoperative wound infections, although the organism was isolated by culture from only one individual at the time of operation. Vandertoll and Beahrs 19 stressed the seriousness of enterocolitis as a complication in reporting the results of 1766 curative anterior resections performed between 1946 and 1957; of the 74 operative (hospital) deaths, 14, or 18.9 per cent, resulted from enterocolitis. The responsible organisms were not described. Polacek and Sanfelippo 15 reported a 27 per cent incidence of diarrhea, and a 23 per cent rate of wound infection, in a sizeable number of patients undergoing open colon anastomoses and prepared with intestinal antibiotics. The control group, prepared for surgery with mechanical measures only, but treated prophylactically with systemic antibiotics postoperatively, fared significantly betterthere was no diarrhea, and a 4 per cent wound infection rate. In our own retrospective study of infection following 1042 colonic resections (12), enterocolitis developed in less than 1 per cent; in eight of the ten cases, antibiotics had been employed in intestinal preparation. There were two deaths, and staphylococci were cultured from the stool in
864
FREDERIC
P.
HERTER
both. Welch and Burke 21 reported three deaths from staphylococcal enterocolitis in over 1300 colorectal operations, an incidence similar to our own. Moving further to the other end of the spectrum, Cohn 5 claimed only one instance of enterocolitis in over 800 patients prepared with kanamycin or a combination of neomycin and tetracyline, and Poth,t 7 who has championed the use of neomycin plus phthalylsulfathiazole (Sulfathalidine) in bowel preparation, denied the occurrence of a single case of pseudomembranous enterocolitis between 1950 and 1964. The discrepancy in the rate of occurrence of this form of "superinfection" between various reporting institutions is of considerable interest. Of greater interest, and probable pertinence, is the fact that staphylococcal enterocolitis, as an entity, has disappeared from· the literature during the past 5 years and has not been a topic of discussion in surgical meetings. During this period, we have not had a single case among our adult population, and I gather that the same phenomenon has obtained at other hospitals. This is not a reflection of any change in our routine of bowel preparation, and we must assume that the particular strain of S. aureus responsible for the almost epidemic appearance of enterocolitis during that earlier decade has indeed disappeared. Support for this assumption comes from the fact that other bacterial strains have similarly made dramatic entries and exits in wound infection studies. Dr. C. W. Findlay, Director of the Meleney Surgical Bacteriology Laboratory at Columbia, informs me that in 1967, Klebsiella occurred in a disproportionately high percentage of our wound infections, as well as a strain of methicillin-resistant staphylococcus. 8 At present, the incidence of infection from bacteroides is on the ascendency, as can be seen in Table 2. It would appear likely that periodic variations in the occurrence and pathogenicity of certain organisms may be anticipated, depending to a degree on antibiotic usage but also on other poorly defined influences beyond our present control. Regardless of the divergent observations and views cited above, there is little question but that an imbalance in the bacterial population of the large bowel, induced by antibiotic therapy, can occasionally lead to a clinically serious emergence of an opportunistic organism. Moreover, the arbitrary use of systemic antibiotics may, in some ill-defined manner, render the host more susceptible to resistant organisms. This matter has been studied experimentally. Dubos and Schaedler/ working with a group of mice free of the normal enteric bacterial pathogens, but not absolutely germ free, found that the protected animals grew more quickly, continued to grow on diets that were deficient to control mice, but were more susceptible than controls to experimental bacterial infections (staphylococcus, Klebsiella, tuberculosis, etc.). Dineen,6 in 1960, pursued these observations further; using a 0.1 per cent concentration of neomycin in the diet, thus lowering the microbial census in the gut, he then challenged mice with an intravenous inocculation of hemolytic S. aureus. The SD-50 for the control animals was 14 days, and for the neomycin-prepared mice 5 days. In addition, the staphylococcus count in the kidneys of the sacrificed neomycin treated animals was significantly higher than in the controls.
865
PREPARATION OF THE BOWEL FOR SURGERY
Table 3.
Prophylactic Antibiotics used in Five University Hospitals, 1964 INFECTION RATE, PER CENT
CLASS OF WOUND
Proph. Antibiotics (4,642 Wounds)
No Antibiotics (10,502 Wounds)
Refined- clean Other Clean Clean- contaminated Contaminated Dirty Inclusive
9.4 11.7 13.9 20.4 31.7 14.3
2.3 5.4 6.8 10.6 22.2 4.4
Supportive of these experimental observations was the clinical study of surgical infection carried out by five university hospitals, mentioned earlier. 18 Patients receiving prophylactic antibiotics had a significantly higher wound infection rate than those untreated by antibiotics, as seen in Table 3. Even adjusting for the large proportion of non-clean wounds in the antibiotic group, there was a disparity in results; the infection rate was 12.2 per cent in the group receiving antibiotics, and 5.2 per cent in the controls. Here again, then, we find suggestive information relating antibiotics to host resistance, although the mechanisms involved are unclear. The second area of contention with respect to antibiotic bowel antisepsis involves the entity of suture-line recurrence. In 1954, Vink 20 published the results of an experimental study in rabbits in which the implantation and growth of inocculated viable tumor cells at the anastomotic line, following colon resection, appeared to be favored by relative bacterial sterility. This study was refined and amplified by Cohn 3 in 1960, with essentially the same findings, namely, that antibiotic control of the intestinal flora increased the possibilities of implantation tumor growth. Although the results of our own attempts to duplicate Vink's work were equivocal, 11 a subsequent clinical study 13 from this institution lent suggestive corroboration to Vink's thesis. Twenty-five documented suture line recurrences were observed following 790 colon resections, an overall incidence of 3.2 per cent. Of particular pertinence was the observation that 15 of the 16 recurrences after anterior resection occurred in patients prepared for surgery with intestinal antibiotics. It thus appears that intestinal antibiotics do carry some degree of threat, both theoretical and actual, with respect to this form of tumor spread, and that this threat must be countered by assiduously applied measures to rid the bowel of viable desquamated tumor cells prior to anastomosis. Ligation of the bowel above and below the tumor prior to its manipulation, irrigation of the divided ends of the bowel with cancericidal agents, and the use of iodized catgut in the anastomosis, all represent suggested methods of avoiding implantation recurrence. In most institutions today, they have become part of the technical ritual of colon resection for cancer.
866
FREDERIC
P.
HERTER
CRITERIA FOR THE USE OF ANTIBIOTICS The foregoing has dealt with the theoretical disadvantages of intestinal antibiotics. Are there compensating advantages, and if so, under what circumstances? Cohn 5 presents a convincing argument for their use-in over 1000 patients prepared for colon surgery with either kanamycin or neomycin and tetracyline, he has encountered no reportable toxicity, a negligible incidence of enterocolitis, and an overall wound infection rate of 10 per cent (13. 7 per cent for colon resections). Unfortunately, he does not have a control group of patients with whom to co:.:npare results. Poth is equally vehement in his defenses of antibiotic preparation. His comparative clinical study in 1960 15 of 170 patients undergoing bowel surgery after a variety of preparatory regimens certainly substantiates his enthusiasm; 18 patients prepared by mechanical measures only, and given antibiotics postoperatively, had an 11 per cent mortality and a 77.7 per cent wound infection rate. In contrast, of 58 patients prepared with neomycin-phthalylsulfathiazole (Sulfathalidine), only 3.4 per cent developed wound infections. When 0.5 per cent neomycin irrigation of the wound at surgery was added to the same preoperative preparation in an additional 59 patients, the wound infection rate was an astounding 1. 7 per cent. Four years later, in a discussion of a paper by Hummel and Altemeier/7 Poth stated that in over 250 open anastomoses performed from 1941 on in patients prepared with antibiotics, he had not a single anastomotic leak, not a single localized abscess, not a single instance of peritonitis, and no operative deaths! No others have come close to duplicating these figures, but additional published reports are supportive. Azar and Drapanos 2 cite a 17.9 per cent wound infection rate in 414 patients prepared with neomycin-phthalylsulfathiazole (Sulfathalidine), as opposed to a 36 per cent infection rate in 31 patients treated with postoperative antibiotics only. Hafner 10 reports a 13.5 per cent infections complication incidence following 200 consecutive colon resections prepared with a variety of chemical agents. The control group is small; 8 of 13 patients, however, prepared by mechanical cleansing only, developed wound infections. A sizeable retrospective study from this institution, 12 designed to better define the influence of chemical bowel preparation, compared 724 patients undergoing colon resection after antibiotic preparation with 318 patients prepared by mechanical measures only. The wound infection rate was 18.2 per cent in the former group, and 24.9 per cent in the controls. The difference was not statistically significant for intraperitoneal anastomoses, however. Only in the anterior resection category did antibiotic preparation appear to hold a substantial advantage; an anastomotic leak rate of 8 per cent contrasted sharply with the 25 per cent rate encountered in unprepared patients, and the overall wound infection rate following anterior resection was 24 per cent for prepared patients and 43 per cent for those unprepared. It was our conclusion that antibiotic preparation should be reserved only for those patients undergoing a resection involving an extraperitoneal anastomosis.
PREPARATION OF THE BOWEL FOR SURGERY
867
Despite the admitted limitations of retrospective clinical investigations, we have not felt compelled to alter the conclusions of that study during the past 4 years. Persuasive though the arguments may appear to be for blanket coverage of all colon operations with preoperative antibiotics, we remain impressed by the subtle though nonetheless real dangers of creating an imbalance in the intestinal flora by such treatment. Additionally, it is our opinion that good mechanical preparation, plus careful surgical technique, are factors of greater importance than chemical antimicrobial therapy in infection control. As such the following indications for antibiotic usage are suggested: 1. Antibiotic bowel preparation should be employed
a. For colon resections entailing an extraperitoneal anastomosis. b. For resective bowel surgery where there is partial obstruction and the possibility of imperfect mechanical preparation. 2. Antibiotic bowel preparation should be omitted in elective intraperitoneal resections for nonobstructing tumors, providing mechanical cleansing is satisfactory. 3. Irrigation of the operative field and wound with a topical antibiotic agent (kanamycin or neomycin-bacitracin) is advisable. 4. Routine prophylactic postoperative antibiotic therapy should be avoided.
CHOICE OF ANTIBIOTICS The most comprehensive study of the effects of antibiotics on the intestinal flora has been carried out by Cohn. 5 Under strict protocol, 48 different agents or drug combinations were investigated with respect to their ability to rid the bowel of streptococci, staphylococci, coliforms, clostridia, and bacteroides. The poorly absorbed sulfa preparations, such as succinylsulfathiazole (Sulfasuxidine) and phthalylsulfathiazole (Sulfathalidine), were found to be inadequate when used alone, as were the various tetracyclines and penicillins. Cohn concluded that the most effective single drug was kanamycin, this based on its lack of toxicity and its activity against all enteric organisms except bacteroides. Neomycin alone was found to be less adequate as an antibacterial, and more toxic; the addition of one of a number of agents (amphotericin, bacitracin, nystatin, polymyxin-B, phthalylsulfathiazole, Thiostrepton) to neomycin, however, produced a highly satisfactory antibiotic combination. Poth 16 has been the principal advocate of the neomycin-phthalylsulfathiazole combination, and his views have received widespread support. No other antibiotic regimen has been employed with greater frequency. Our laboratory of Surgical Bacteriology has found neomycin to have the same spectrum of antibacterial activity as kanamycin; moreover, the nausea, vomiting, and diarrhea cited by Cohn as toxic manifestations of neomycin administration have been virtually absent in our experience. It has been used as the single agent of choice in this institution for several years, not because of its documented superiority over kanamycin, but because of familiarity with use and demonstrated effectiveness. A combination of neomycin and bacitracin had previously been employed routinely in bowel preparation (in no small part because bacitracin had been
868
FREDERIC
P.
HERTER
developed at this institution), but there are no hard statistical data from our laboratory to indicate that this combination was more advantageous than neomycin alone. Cohn's studies suggest that bacteroides are better controlled by neomycin-bacitracin than by neomycin alone, and in view of the recent upsurge in serious bacteroides infections at this hospital, we probably would be well advised to reconsider the use of the combination again. Although phthalylsulfathiazole (Sulfathalidine) alone appears to have little activity against bacteroides, its combination with neomycin appears to be highly effective in Cohn's hands in suppressing this class of organisms well beyond the treatment period. Given the current increase in bacteroides wound infections, then, we would favor either of the above combinations over kanamycin or neomycin alone. Although Poth has advocated a 24 hour period of antibiotic bowel preparation only, theoretically based on the possible emergence of resistent strains with longer treatment, Cohn's observations suggest that complete bacterial control is not effected in such a short period. He advises treatment of 72 hours' duration. My personal preference, which I confess has a largely empirical basis, strikes a compromise between the two-namely, 36 hours. Antibiotic therapy is begun on the afternoon of the second day before surgery, accordingly to the following schedule: Second preoperative day: Neomycin, 1 gm. plus bacitracin, 40,000 units or Sulfathalidine, 1.5 gm., at 1, 2, 3, 4, and 10 o'clock in the P.M. First preoperative day: Neomycin, 1 gm., plus bacitracin, 40,000 units of sulfathalidine, 1.5 gm., at 4 and 10 o'clock in the A.M., and 4 and 10 o'clock in the P.M.
DISCUSSION The principal reason that controversy continues to exist in this important area of surgery is that no large scale randomized, prospective clinical study, comparing antibiotic preparation of the bowel with mechanical preparation alone, has ever been completed. Such a study should be carried out in a single institution, and involve the same group of surgeons operating with highly standardized surgical techniques. The case sampling must be large enough to allow for comparable pathologic and clinical material; mechanical measures to cleanse the bowel should be applied consistently, and insofar as possible, with uniformity; and bacteriologic data should be collected and analyzed under strict protocol. This type of undertaking is at best difficult and time-consuming, considering the number of variables, but it must be done if empiricism and emotionalism are to be eliminated from our thinking. Cohn has introduced order into the evaluation of the various antibiotic agents available for intestinal preparation; what he has not answered, however, is the basic question as to whether intestinal antibiotics add measurable protection from infection over and above that provided by mechanical preparation alone plus careful surgical technique. Nor have the innumerable other contributors to this literature-there are almost as many de-
PREPARATION OF THE BOWEL FOR SURGERY
869
tractors as there are antibiotic supporters. Our efforts to arrive at conclusions through retrospective analyses have been somewhat less than satisfactory, as might have been anticipated. The variables are too great to reconcile retrospectively, and the lack of randomization of case material permits inevitable bias in choice of management to enter in. Thus certain conclusions or impressions arrived at herein with respect to the use of antibiotics admittedly emanate from an insecure data base and must be considered tentative, pending the prospective investigation outlined above.
SUMMARY AND CONCLUSIONS Wound infection rates following open operations on the colon and rectum remain high, and call for a reevaluation of methods of bowel preparation. Mechanical preparation, through diet reduction, purgation, and enemata, is of paramount importance, whether or not antibiotics are em-ployed. A regimen for mechanical cleansing of the bowel is suggested. Arguments for and against the use of intestinal antibiotics are presented, relating particularly to "superinfection," suture line recurrence, and possible changes in host resistance to infection. Antibiotic preparation is advocated in the presence of partial bowel obstruction, where mechanical measures may be unsatisfactory, and for resections in which an extraperitoneal anastomosis is anticipated. Both kanamycin and neomycin, the two single most effective agents against enteric pathogens, fail to control bacteroides, the source of many recent wound infections, and the addition of bacitracin or Sulfathalidine is recommended.
REFERENCES 1. Altemeier, W. A., Hummel, R. P., and Hill, E. 0. Prevention of infection in colon surgery. Arch. Surg., 93:226, 1966. 2. Azar, H., and Drapanos, T.: Relationship of antibiotics to wound infection and enterocolitis in colon surgery. Amer. J. Surg., 115:209, 1968. 3. Cohn, I., Jr., and Atik, M.: The influence of antibiotics on the spread of tumors of the colon. Ann. Surg., 151 :917, 1960. 4. Cohn, I., Jr.: Discussion of paper by Hummel, R. P., Altemeier, W. A., and Hill,'E. 0., Ann. Surg., 160:551, 1964. 5. Cohn, I., Jr.: Intestinal Antisepsis. Springfield, Illinois, Charles C Thomas, 1968. 6. Dineen, P.: Effect of reduction of bowel flora on experimental staphylococcal infection in mice. Proc. Soc. Exper. Biol. Med., 104:760, 1960. 7. Bubos, R. S., and Schaedler, R. W.: The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections. J. Exper. Med., 110:935, 1959. 8. Findlay, C. W., Jr.: Personal communication, 1971. 9. Garlock, J. H., and Seley, G. P.: The use of sulfanilamide in surgery of the colon and rectum. Preliminary report. Surgery, 5:787, 1939. 10. Hafner, C. D.: Antibiotics in colon surgery. Amer. J. Surg., 121:673, 1971. 11. Herter, F. P., Santulli, T.V., Terry, S., Buda, J. A., and Beals, R. L.: An experimental study of the influence of the intestinal bacterial flora on suture line recurrence following resection for carcinoma of the colon. Surg. Gynec. Obstet., 114:267, 1962.
870
FREDERIC
P.
HERTER
12. Herter, F. P., and Slanetz, C. A., Jr.: Influence of antibiotic preparation of the bowel on complications after colonic resection. Amer. J. Surg., 113:165, 1966. 13. Herter, F. P., and Slanetz, C., Jr.: Preoperative intestinal preparation in relation to the subsequent development of cancer at the suture line. Surg. Gynec. Obstet., 127:49, 1968. 14. Hummel, R. P., Altemeier, W. A., and Hill, E. 0.: Iatrogenic staphylococcal enterocolitis. Ann. Surg., 160:551, 1964. 15. Polacek, M.A., and San Felippo, P.: Oral antibiotic bowel preparation and complications in colon surgery. Arch. Surg., 97:412, 1968. 16. Poth, E. J.: The role of intestinal antisepsis in the preparative preparations of the colon. Surgery, 47:1018, 1960. 17. Poth, E. A.: Discussion of paper by Hummel, R. P., Altemeier, W. A., and Hill, E. 0.: Ann. Surg., 160:551, 1964. 18. Report of an Ad Hoc Committee of the Committee on Trauma, Division of Medical Sciences, National Research Council, National Academy of Sciences: The influence of ultaviolet irradiation of the operating room and various other factors. Ann. Surg., 160(Suppl.):1-192, 1964. 19. Vandertoll, D. J., and Beahrs, 0. H.: Carcinoma of the rectum and low sigmoid; evaluation of anterior resection of 1766 favorable lesions. Arch. Sug., 90:193, 1965. 20. Vink, M.: Local recurrence of cancer in the large bowel; the role of implantation metastases and bowel disinfection. Brit. J. Surg., 41:431, 1954. 21. Welch, C. E., and Burke, J. F.: Carcinoma of the colon and rectum. New Eng. J. Med., 266:2.11-219, 1962. Department of Surgery Columbia University College of Physicians and Surgeons 630 West 168th Street New York, New York