Antibiotic Prophylaxis in Gastric, Biliary and Colonic Surgery

H. HARLAN STONE, M.D., C. ANN HOOPER, B.S., B.A., LAURA D. KOLB, B.S., CAROL E. GEHEBER, B.S., E. JANELLE DAWKINS, B.S.

Antibiotic prophylaxis for surgery has appeared indicated when- From the Joseph B. Whitehead Department of Surgery, ever likelihood of infection is great or consequences of such are Emory University School of Medicine, catastrophic. For better clarification, a prospective, randomized, 69 Butler St., S.E., Atlanta, Georgia 30303 double-blind study was run on 400 patients undergoing elective gastric, biliary, and colonic operations. There were four treatment categories, with antibiotic being instituted 12 hours preoperatively, just prior to operation, after operation, or not at all. were During operation, samples of blood, viscera, muscle, and fat were could then likewise be reduced if less hospital days taken for determination of antibiotic concentration. Both aerobic consumed and if reoperation for some complicating in- and anaerobic cultures were also taken of any viscus entered, fection were not as frequently required; while antibiotic peritoneal cavity, and incision. Similar cultures were run on all use might even be decreased if fewer postoperative postoperative infections. Results demonstrated that the incidence infections developed and, especially, if the duration of of wound infection could be reduced significantly by the preopera- antibiotic prophylaxis was cut to a bare minimum. tive administration ofantibiotic in operations on the stomach (22% to 4%), on the biliary tract (11% to 2%), and large bowel (16% to Nevertheless, potential harm resulting from routine 6%). Less impressive results were obtained for peritoneal sepsis. antibiotic therapy cannot be ignored. Drug toxicity, Initiation of antibiotic postoperatively gave an almost identical allergic reactions, and in particular the evolution of infection rate as if antibiotic had not been given (15% and 16%, resistant bacterial strains certainly appear to be potential respectively). if not actual significant threats. TrHE VALUE as well as dangers of prophylactic antibiotics has been hotly debated for the past three Clinical Trial decades. Lack of concrete data, as might be derived from To evaluate these several aspects of prophylactic anti- either rigidly controlled laboratory studies or prospective biotic therapy as well as to confirm the already reported randomized clinical trials, has by no means limited these benefits of its application, a prospective randomized and arguments. Only the animal experiments of Burke4 and double-blinded study was carried out on the surgical relatively sophisticated clinical trials by Polk,10, Ledger,7 wards of Grady Memorial Hospital. After 20 months (the and a few others have given any true insight as to the trial period ending February 29, 1976), 400 consecutive benefits of such a program.1 3'4'8 9 All other supportive re- patients admitted for elective operations on the stomach, ports have primarily been emotional claims, based upon biliary tract, and/or colon had been enrolled in the study. either poorly or totally uncontrolled scientific evidence. The only exceptions to inclusion into the study were There are, in addition, other advantages that might be antibiotic therapy with parenteral or orally absorbable gained through the administration of prophylactic anti- agents during the 10 days immediately preceding opera- biotics. Hospital beds possibly could be conserved tion, conditions present that already demanded antibiotic through a shortened average patient stay. Hospital costs prophylaxis (i.e., heart valve disease), known allergy to a cephalosporin, and an age of less than two years. Pa- tients colon surgery, however, did receive 1 Presented at the Annual Meeting of the American Surgical Associa- undergoing tion, New Orleans, Louisiana, April 7-9, 1976. gm of oral neomycin every 4 to 6 hours for two days Supported in part by a grant from Eli Lilly and Company. prior to operation as well as 500 mg of erythromycin

443 444 STONE AND OTHERS Ann. Surg. o October 1976 base every 6 hours for 24 hours preoperatively. Routine of the contents of the organ subjected to operation, attempts were made to preclude any consideration of the peritoneal cavity, and the subcutaneous portion of the antibiotic prophylaxis with respect to decision for incision at the time of closure. Sensitivity testing was operation, procedure performed, and general postoper- subsequently run on all aerobic isolates to the 30 mcg ative care. disc of cefazolin.2 Antibiotic Administration Followup Each patient was given an intramuscular injection of Postoperatively, all patients were carefully followed for either antibiotic (I gm of tefazolin) or placebo (equiv- evidences of infection developing within the abdomen alent volume of diluent) on the evening before opera- and/or surgical incision. In addition, complicating infection, on call to the operating room and on that same tions in other areas were specifically noted. Appropriate evening after return to either the ward or the intensive aerobic and anaerobic cultures were taken from all sites care unit, on the morning of the day following surgery, of known as well as even suspected sepsis. Aerobic and again during the evening of the first postoperative bacterial isolates were also tested for sensitivity to the day (Fig. 1). Scaled down doses were used for children, prophylactic antibiotic, i.e., cefazolin, at a 30 mcg disc with weight being the prime determinant. The solutions size.2 for injection had previously been assembled in patient Complications of drug therapy, other postoperative number packets, so that there were five vials in each pack problems, total as well as postoperative hospital stay, and each vial was coded as to time when it should be all details related to indications for surgery, type of given. Details in randomization were unknown to all con- operation, general status of the patient, and, finally, cerned with patient care, although the master key was eventual outcome were faithfully recorded. These items readily available in the event that a possible drug or were later used to confirm the purity of the randomiza- infectious complication demanded that the code be tion process plus the identification of any significant broken. influence, other than the prophylactic antibiotic, on the Drug dosage had been set up so that equal numbers incidence of subsequent infection. of patients had their prophylactic antibiotic initiated approximately 12 hours preoperatively, one hour prior to Results operation, or within an hour following completion of the operation (Fig. 1). Twenty-five per cent of the patients At the completion of the clinical trial, there were 100 received no antibiotic at all. When given, cefazolin was patients for analysis in each treatment category. Gastric administered in three consecutive injections for a total surgery had been performed on 96, a biliary tract dose of 3 gms over a period of approximately 24 hours. procedure on 131, and colon surgery on 190-thereby No other antimicrobial was given thereafter, that is, giving a total of 417 operations. The extra 17 were ac- unless an established infection could be documented counted for by the fact that these patients had had a or the patient's clinical course became highly suggestive surgical procedure carried out in two, rather thanjust one, of a developing septic complication. area of study. Ages ranged from 2 to 86 years, with an average of47.6. Sampling During Operation There were 179 males and 221 females; 312 were Negro, while 88 were Caucasian. No significant difference At surgery, 9 specific specimens could were taken. An at- be found between the four assigned treatment groups tempt was generally made to obtain all samples within with respect to type of operation, a indication for surgery, few minutes of each other. Once the abdomen had been age, sex, or race. opened, both peripheral as well as portal venous blood There were four postoperative deaths, three of which were drawn for determination of antibiotic blood levels. occurring in patients who had Likewise, liquid had two procedures done contents ofthe organ ofoperation (gastric at the one operation. Otherwise, no major difference was juice, bile, and/or colon contents) were obtained for apparent between the several therapy categories. similar analyses of antibiotic concentration. A modified well-diffusion technique was used for these studies.13 Antibiotic Distribution Biop§ies of viscera resected as well as abdominal wall muscle and subcutaneous fat were also taken. These Concentrations of cefazolin were not significantly specimens were immediately frozen and then sent at inter- different when portal was compared to peripheral venous vals to the Lilly Research Laboratories for determina- blood (Table 1). The average value was 13.7 mcg/ml. tion of antibiotic tissue concentration. Administration of cefazolin 8 to 12 hours prior to Finally, both aerobic and anaerobic cultures were taken operation gave approximately 40% higher tissue levels Vol. 184oNo. 4 ANTIBIOTIC PROPHYLAXIS 445 PRE-OP DAY OF POST-OP GROUP DAY 1 OPERATION DAY A GROU l|AM PM-t AM |PM ||AM |PE FIG. 1. Times of antibiotic administration. Placebo injections are indicated by an I x x x 0 0 "O"; cefazolin was given at times marked by an "X." Ii 0 X X X 0 III 0 0 X X X IV 0 0 0 0 0

than if the antibiotic had been started a mere hour pre- lactic antibiotic had been started preoperatively (Table 2). operatively (Table 1). Concentrations of cefazolin in sub- Results were much more impressive with procedures on cutaneous fat were less than half that of the blood when- the colon than for operations on the stomach and biliary ever antibiotic therapy had been instituted only an hour tract. However, no real difference could be discerned before hand. In fact, antibiotic concentrations in fat and in between the two groups receiving preoperative cefazolin, bowel wall were consistently below values discovered in that is, between those patients having such therapy other tissues. Stomach and gallbladder had biologically instituted 8 to 12 hours prior to operation and those measurable concentrations of cefazolin in their walls that whose antibiotic was not begun until just an hour before even surpassed concomitant blood levels, yet such may surgery. By contrast, the incidence of peritoneal sepsis well have been due to the additive bacteriocidal effect was essentially the same as if no antibiotic had been of acid and bile, respectively. given whenever cefazolin administration had been put off Analyses of bile and gastric juice for cefazolin until after operation. concentrations were undoubtedly spurious because of Differences in wound infection rate were much more their already known antimicrobial actions (Table 1). dramatic than were those for intraperitoneal sepsis (Table Similarly, the preoperative administration of oral neo- 3). Overall, there was an almost four-fold greater inci- mycin and erythromycin base may well have accounted dence of infection within the incision when antibiotic for the apparent presence of study antibiotic in colon was withheld than when such had been given preopera- contents, irrespective as to whether cefazolin had been tively. Initiating cefazolin therapy after operation gave administered preoperatively or not. approximately the same results as if the parenteral antibiotic had been completely withheld. All of these Incidence ofInfection figures were highly significant (P = .01). As with intraperitoneal infection, results obtained in the two preoper- The reduction in incidence of intraperitoneal sepsis ative treatment groups were almost identical. was relatively significant (P = 0.05) whenever prophy- Table 2. Peritoneal Infection Table 1. Distribution of Chefazolin at Operation: Antibiotic Administered Preoperatively Antibiotic Begun Area Antibiotic Begun of 8-12 hr I hr 1-4 hr Never Preoperatively Operation Preop Preop Postop Given Totals

8-12 Hours 1 Hour Gastric 22 27 24 23 96 Infected 1 1 1 2 5 Peripheral venous blood mcg/ml 14.1 13.5 Incidence 5% 4% 4% 9%o 5% Portal venous blood mcg/ml 13.8 13.4 Biliary 29 31 33 38 131 Abdominal muscle mcg/gm 14.0 9.3 Infected 1 0 1 1 3 Subcutaneous fat mcg/gm 9.8 6.3 Incidence 3% - 3% 3% 2% Gastric secretions mcg/ml 14.3 11.2 Colonic 54 47 46 43 190 Bile mcg/ml 22.5 21.4 Infected 1 1 3 3 8 Colon contents mcg/ml 22.3 20.4 Incidence 2% 2% 7% 7% 4% Stomach wall mcg/gm 15.9 12.9 Totals 100 100 100 100 400 Gall bladder wall mcg/gm 21.3 14.9 Infected 2 2 5 6 15 Colon wall mcg/gm 11.0 9.8 Incidence 2% 2% 5% 5% 4% 446 STONE AND OTHERS Ann. Surg. EOctober 1976 Table 3. Wound Infection Table 4. Bacterial Contamination and Wound Infection Antibiotic Begun Operative Culture of Wound Area and Peritoneum of 8-12 hr I hr 1-4 hr Never Operation Preop Preop Postop Given Totals Antibiotic Positive Positive Negative Begun Culture Staph. Culture Gastric 22 27 24 23 96 Infected 1 1 4 5 11 Preoperative 96 13 104 Incidence 5% 4% 17% 22% 11% Infected 7 1 0 Biliary 29 31 33 38 131 Incidence 7% 8% 0% Infected 1 0 3 4 8 Postoperative 55 10 45 Incidence 3% 9% 11% 6% Infected 13 3 1 Colonic 54 47 46 43 190 Incidence 24% 30%W 2% Infected 3 3 7 7 20 Never given 49 12 51 Incidence 6% 6% 15% 16%c 11% Infected 14 3 1 Totals 100 100 100 100 400 Incidence 29% 25% 2% Infected 4 3 14 15 36 Incidence 4% 3% 14% 15% 9% sional sepsis when all intraoperative wound as well as Bacterial Contamination peritoneal cultures had been negative (Table 4). Although the majority of bacterial isolates recovered Exactly half of the patients had positive cultures of the from organs of operation could be classified as gram- wound and/or peritoneum at the time of operation; and, negative rods, such species were even more predominant of these, 35 or 17.5% had Staphylococcus aureus as one in operations on the colon (Table 5). In addition, of the bacterial contaminants (Table 4). Preoperative anaerobes and Enterococcus were also plentiful in the antibiotic prophylaxis gave a wound infection rate of only colonic flora. Antimicrobial sensitivity of the 790 7% in those patients with culture proven contamination; aerobic isolates obtained at operation was 74.8% to the 30 while postoperative cefazolin administration or no anti- mcg cefazolin disc. On the other hand, the actual and biotic treatment at all produced infection rates of 24% not just potential contaminants (i.e., isolates from the and 29%, respectively, for the same degree of bacterial wound and/or peritoneum alone) had a much greater contamination. The incidence of wound infection due to susceptibility to cefazolin (91.2%) (Fig. 2). Aerobic Staphylococcus aureus was similarly affected in both bacteria cultured from all complicating wound and treatment groups by the action of preoperative prophy- peritoneal infections, however, had sensitivities that lactic therapy. averaged only 39% (Table 5 and Fig. 2). A striking contrast to this increased incidence of in- The total number of bacteria contaminating the wound fection was the exceedingly rare development of inci- also appeared to influence the likelihood of subsequent

TABLE 5. Bacterial Sensitivities to Cefazolin: Testing to 30 mcg Antibiotic Disc. Gastric Isolates Biliary Isolates Colon Isolates Total Initial Infection Isolates Per cent Per Cent Per Cent Per Cent Per Cent Species Isolated Number Sensitive Number Sensitive Number Sensitive Number Sensitive Number Sensitive E. coli 49 47 31 30 159 137 239 90%G 18 61% E. species 4 2 2 2 8 6 14 71% - - Klebsiella-Enterobacter 6 5 2 2 16 15 24 92% 8 38% Klebsiella species 32 31 13 12 58 54 103 94% 8 75% Proteus mirablis 13 12 3 3 17 16 33 94% 4 50%c Proteus species 8 1 2 0 38 10 48 23% 12 68% Pseudomonas 6 0 0 21 0 27 O% 7 0% Other G-neg rods 13 13 8 4 7 6 28 82% 10 10% Staph aureus 24 24 36 34 33 32 93 97% 11 64%o B. Streptococcus 3 3 1 1 2 2 6 10%- Enterococcus 43 22 18 4 205 54 266 30%o 22 9W Misc. aerobes 4 4 0 5 3 9 78%- Bacteroides 23 * 6 * 52 * 81 * 2 * Eubacteria 13 * 4 * 32 * 49 * I * Pepto & Peptostrepto 17 * 3 * 16 * 36 * 1 * Clostridia 10 * 5 * 21 * 36 * * Misc. anaerobes 79 * 27 * 69 * 175 * 18 * C. albicans 3 * 0 * 6 * 9 * 0 *

* Sensitivities not run. Vol. 184 a No. 4 ANTIBIOTIC PROPHYLAXIS 447 no way altered the infection rate when the contaminating bacteria were already resistant to the antimicrobial 100 agent given, i.e., cefazolin. C') z This relationship of number of bacterial species to incidence of complicating infection was dramatically re- cog~ flected in the culture data as well as the disease process u)E 0 for which gastric operations were done (Table 6). Hyper- acidity was associated with a relatively sterile stomach (02-o lumen and accordingly resulted in only a single postopera- 0= tive infection. Such contrasted strikingly to the 30%o L)002 average infection rate when surgery was performed for z 0 gastric cancer or a benign gastric ulcer. 0

0 . Cause ofInfection 1%1*1 All seven of the wound infections occurring in patients who received preoperative antibiotic could be ex- Pm-operativ Post-0pative Never Given plained, at least on theoretical grounds, by a wound and/or peritoneal contamination by cefazolin-resistant bacteria TIME OF BEGINNING ANTIBIOIlC (Table 7). One of the patients, in addition, had an anti- FIG. 2. Antibiotic sensitivities of the bacterial isolates. Bacterial biotic concentration in his subcutaneous fat which might susceptibility to 30 mcg discs of cefazolin is charted according to well be deemed insufficient for the control of an inoculum time of initiating antibiotic therapy. Shaded bars represent results obtained from taking initial isolates, while the clear bars reflect sensitivities containing otherwise susceptible pathogens. of bacteria cultured from subsequent wound and/or peritoneal Patients who never received preventative antibiotic infections. or whose antimicrobial therapy was begun in the postoperative phase had infection rates, specifically due to infection (Fig. 3). This was especially true in patients cefazolin-resistant bacteria, that were almost identical not given preoperative antibiotic or in whom cefazolin to what had been noted for the preoperative treatment administration was delayed until the patient had reached groups (Table 7). However, none of the tissues of the the recovery room. Nevertheless, antibiotic therapy in late or not-treated patients contained antibiotic-a

80 PREIOPE.pATIV/E I CEFAZOLIN NEVER OR CEFA2ZOLIN POST- OPERATIVELY 06O 60

z FIG. 3. Relationship of the number ofbacterial species Z 40 contaminating the incision 0 at the time of wound clos- / ure and incidence of sub- IL sequent wound infection. 0 0 Z 20 b o--o Cefozwin ms=stant Ir . sC,n

I I I I I, I I I I 2 3 4 5 5+ 1 2 3 4 5 5+ NUMBER OF BACTERIAL SPECIES ISOLATED (from incision at time of closu) 448 STONE AND OTHERS Ann. Surg. v October 1976 TABLE 6. Wound Infection After Gastric Surgery: Influence such infectious complications developing was least for the of Indication for Operation group receiving antibiotic just an hour prior to operation Number Infected Incidence (Table 8). No adverse reactions were noted, either locally or Duodenal ulcer 48 1 2% Gastric ulcer 14 4 29%o systemically, from the use of cefazolin. Likewise, there Gastric cancer 13 4 31% was not a single case of drug allergy. Pancreatic pseudocyst 17 1 6% Other 4 1 25% Financial Considerations Tabulation ofthe average number ofpostoperative days situation to be expected when cefazolin was not circulat- required by all patients revealed that an incisional in- ing in the a blood-and thus provided plausible explana- fection was associated with an extra 15.6 tion for subsequent hospital days infection due to cefazolin-susceptible (Table 9). At a per diem rate of $80.00 a day, the microbes. minimal additional expenditure for a single wound infection was $12,048.00 per patient, exclusive of all Antibiotic Resistance supplemental laboratory tests, drug therapy, and second Although 75% of aerobic bacteria colonizing the visceral operations. contents (Table 5) and 91% of aerobic isolates initially If financial considerations were, instead, analyzed ac- obtained from the incision and/or peritoneum (Fig. 2) were cording to therapy group, a significantly different pattern sensitive to the action of cefazolin, antibiotic therapy became apparent (Table 10). The average excess post- reduced this rate of drug susceptibility to 39o for operative stay was 1.5 days for patients beginning those bacteria responsible for subsequent wound infec- cefazolin postoperatively and 2.9 days for those never tion. This was true for all patients receiving preventive receiving the antibiotic in comparison to the two pre- therapy, irrespective as to whether the antimicrobial operative treatment groups. Such additional hospital days had been started before or after surgery. However, if increased the total hospital cost by $120.00 and $232.00 cefazolin had never been given, the percentage of anti- per patient, respectively. By contrast, the cost of pre- biotic sensitive isolates was approximately the same as ventive antibiotic therapy was negligible, that is, only had been noted from bacteria initially cultured from the $13.47 per patient. incision and/or abdominal cavity at the time of operation (Fig. 2). Discussion Other Infections Three basic factors, acting singly or in combination, appear to be responsible for the development of a The likelihood of infection developing in areas outside postoperative wound infection. These are: 1) a bacterial the wound and peritoneum was not significantly altered inoculum of sufficient numbers as well as of necessary by antibiotic administration, even though the number of virulence; 2) a local substrate upon which the con-

TABLE 7. Reasons for Postoperative Wound Infection Antibiotic Begun 8-12 hr I hr 1-4 hr Never Cause/relationships Preop Preop Postop Given Totals Total number of infections 4 3 14 15 36 Bacteria resistant to antibiotic Isolates from organ 4 2 4 5 15 Isolates from peritoneum 4 3 3 6 16 Isolates from wound 3 2 3 7 15 Insufficient antibiotic concentration In tissue Organ 0 1 14 15 30 Muscle 0 0 14 15 29 Fat 0 1 14 15 30 In fluid Juice 1 1 11 11 24 In blood Peripheral 0 0 14 15 29 Portal 0 0 14 15 29 Other or unknown 1 1 2 1 5 VOl. 184 . NO. 4 ANTIBIOTIC PROPHYLAXIS 449 TABLE 8. Infections Outside the Area of Operation TABLE 9. Hospital Economics Antibiotic Begun Wound No wound Area Infection Infection of 8-12 hr 1 hr 1-4 hr Never Inci- Infection Preop Preop Postop Given Totals dence Patients 36 364 Postop hospital days 931 3736 Patients 100 100 100 100 400 Average postop days 25.9 10.3 Urinary 10 12 7 7 36 9%O Average excess days 15.6 Pulmonary 4 0 3 3 10 3% Minimal excess cost $1248.00 per patient Bacteremia 2 0 4 2 8 2% ($80.00 per diem) Other I 1 4 5 11 3% Totals 17 13 18 17 65 16%O authors have stressed, without exception, is that the antimicrobial agent must be started prior to operation. Post- taminating microbes can live as well as propagate; and operative initiation of antibiotic therapy has appeared to 3) some impairment, be it local or systemic, in host be of no true benefit in reducing the incidence of wound resistance. sepsis, only in making such infectious complications Preoperative measures, such as intestinal cleansing, less lethal and perhaps more confined to a given region antiseptic skin preparation, and operation within a or compartment.11 relatively sterile environment represent attempts at reduc- At present, prophylactic antibiotic therapy seems indi- ing the absolute quantity of the bacterial inoculum. cated whenever: 1) the consequences of wound infec- However, once contamination has occurred, the size of tion are uniformly disastrous, even though the occurrence the inoculum still can be diminished by a careful wound of this sepsis is uncommon; 2) the incidence of wound toilet with removal of all gross material and then the infection is great, yet seldom does it ever threaten life selective application of some topical antibiotic."1 On the or limb; and 3) the patient has such an extreme impair- other hand, creating a wound that is less hospitable to ment in host defense mechanisms that any infection, bacterial colonization and thus to subsequent infection no matter how minor, has a propensity for becoming is primarily a product of the dedication and ability of systemic and thereby fatal. the surgeon. It is his technical skill, meticulous atten- Accordingly, the benefits to be accrued from a pre- tion to detail, and gentle handling of tissues that curbs ventive antibiotic program include reductions in both the amount of clot and cellular necrosis and thus the morbidity and mortality. Additional and certainly less ready availability of nutrition to any bacterial inoculum. humane-sounding advantages are a conservation of In this setting, the prophylactic role of a parenterally hospital bed space and the potential for great savings in administered antibiotic is merely to increase local tissue moneys to be expended for individual patient care. resistance against the majority, if not all, of the in- The application of prophylactic antibiotics to clinical vading pathogens. This it appears to do quite effectively, practice should be based solely on need. This can be even though certain limitations are to be expected and identified only through an effective hospital surveillance specific requirements must be met. 1'3-5'7-10 program, whereby operative cases are followed and the Prophylactic antibiotics have been documented to be of incidence of postoperative sepsis for a given surgical considerable value in reducing the incidence of wound procedure is then calculated at relatively frequent inter- infection in several areas of surgery.13'57-10 Many of vals.6 However, it must be emphasized that preventive these claims have true scientific merit and are based upon antibiotics can never substitute for excellence in opera- prospective, randomized trials of antibiotic versus a tive skills, patient and procedure selection, thoroughness placebo. Unfortunately, however, there are approxi- of postoperative care, and, most important of all, operat- mately 50 poorly-founded and retrospectively reviewed ing room hygiene. "testimonials" for every one controlled and statistically significant study. TABLE 10. Cost Comparisons Without doubt, the hallmark is the report by Polk and Preop Postop No Lopez-Mayor.10 Their studies on elective colon surgery Antibiotic Antibiotic Antibiotic demonstrated a highly significant reduction in wound Patients 200 100 100 infection rate whenever cephaloridine was given just Postop hospital days 2113 1208 1346 prior to operation. Later investigators have followed suit Average postop days 10.6 12.1 13.5 Average excess days Per patient 1.5 2.9 and, using the same or entirely different antibiotics, Minimal excess cost Per patient $120.00 $232.00 have shown remarkably good results in more distant ($80.00 per diem) anatomical areas, such as with operations on the biliary Cost of antibiotic $13.47 $13.47 Per patient Excess expenditure tract,5 hysterectomy,1'7 compound fractures,8 and clean per patient $13.47 $133.47 $232.00 orthopedic surgery.3'9 The one consideration that all 1976 450 STONE AND OTHERS Ann. Surg. * October Once the need for prophylactic antibiotic has been organ resected, abdominal muscle and subcutaneous fat justified because of a proven significant incidence of were taken for determination of antibiotic concentra- wound infection after surgery in a certain area or operation. Both aerobic and anaerobic cultures were also tion for a specific patient condition, the responsible taken of any hollow viscus entered, peritoneal cavity, bacteria must then be tabulated as a part of the same and abdominal incision at closure. Similar cultures were surveillance procedure.6 From such data, plus informa- run on all postoperative infections. tion available from both the literature as well as the Results demonstrated that the incidence of wound in- hospital laboratory on antimicrobial sensitivities of these fection could be cut significantly by timely administration responsible pathogens, several antibiotics can be intelli- of prophylactic antibiotic in operations on the stomach gently evaluated for possible use in a preventive (22% to 4%), on the biliary tract (11% to 2%) and large program. Prime considerations are: 1) a reported as well bowel (16% to 6%), all with P values of .01. Less as the individual hospital experience confirming specific impressive results, though almost as significant (P = 0.05), antibiotic effectiveness against the anticipated path- were obtained for peritoneal sepsis. However, for pro- ogens; 2) lack of toxicity and rare allergic reactions; phylaxis to be successful, the antibiotic had not only 3) a tissue distribution that will permit the antimicrobial to be effective against anticipated bacterial con- agent to reach those body areas with a known predilec- taminants, but present in the circulating blood and, more tion for postoperative infection and in concentrations especially, in local tissues at the time of contamina- known to be effective; 4) an established time/dose/route tion. Indeed, initiation of antibiotic postoperatively gave relationship that will assure antibiotic tissue levels at almost the same wound infection rate as if antibiotic the time of anticipated contamination4; 5) elimination of had not been given at all (15% and 16%, respectively). all antimicrobial agents which presently serve (or have Evolution of antibiotic resistant bacterial strains and no immediately available substitute) as first choice anti- greater hospital economy in beds and money were addi- biotics for the more usual postoperative infections, such tional important considerations. as those of the wound or peritoneum; and 6) expected cost of preventive drug therapy for each individual antibiotic under consideration. References From such information, a practical selection as to 1. Allen, J. L., Rampone, J. F., and Wheeless, C. R.: Use of a specific antibiotic for a given operation can then be made. Prophylactic Antibiotic in Elective Major Gynologic Opera- In the future, tions. Obstet. Gynecol., 39:218, 1972. cephalosporins will probably be the single 2. Bauer, A. W., Kirby, W. M. M., Sherris, J. C., and Turk, M.: group of drugs most commonly employed, although re- Antibiotic Susceptibility Testing by a Standardized Single Disc quirements will indeed vary from hospital to hospital be- Method. Am. J. Clin. Pathol., 45:493, 1966. cause 3. Boyd, R. J., Burke, J. F., and Colton, T.: A Double-Blind of entirely different infectious problems to be over- Clinical Trial of Prophylactic Antibiotics in Hip Fractures. J. come. Thus, considerable variation in the exact prophy- Bone Joint Surg., 55-A:1251, 1973. lactic antibiotic program should be expected and even 4. Burke, J. F.: The Effective Period of Preventive Antibiotic Action in Experimental Incisions and Dermal Lesions. Surgery, encouraged. Nevertheless, it is extremely important that 50:161, 1961. preventive treatment not be abused. Otherwise, surgical 5. Chetlin, S. H., and Elliott, D. W.: Preoperative Antibiotics in skills will deteriorate; and antibiotic-resistant microbes Biliary Surgery. Arch. Surg., 107:319, 1973. may then become even more 6. Cruse, P. J. E., and Foord, R.: A Five-Year Prospective dominant in the standard Study of 23,649 Surgical Wounds. Arch Surg., 107:206, 1973. hospital flora than they now are.12 7. Ledger, W. J., Sweet, R. L., and Headington, J. T.: Prophylactic Cephaloridine in the Prevention of Postoperative Pelvic Infec- tions in Premenopausal Women Undergoing Vaginal Hyster- Conclusions ectomy. Am. J. Obstet. Gynecol., 115:766, 1973. Antibiotic prophylaxis 8. Patzakis, M. J., Harvey, J. P. and Ivler, D.: The Role of Anti- against sepsis following elective biotics in the Management of Open Fractures. J. Bone Joint surgery has appeared indicated whenever likelihood of Surg., 56-A:532, 1974. infection is great or consequences of such, though rare, 9. Pavel, A., Smith, R. L., Ballard, A., and Larsen, I. J.: Prophylactic are catastrophic. For better the Antibiotics in Clean Orthopaedic Surgery. J. Bone Joint Surg., clarification, value of pre- 56-A: 777, 1974. ventive antimicrobials was assessed in a prospective, 10. Polk, H. C., Jr., and Lopez-Mayor, J. F.: Postoperative Wound randomized, double-blind study of 400 patients under- Infection: A Prospective Study of Determinant Factors and going elective gastric, biliary, and colonic operations. Prevention. Surgery, 66:97, 1969. There were 11. Stone, H. H., and Hester, T. R., Jr.: Incisional and Peritoneal four treatment categories, with antibiotic Infection After Emergency Celiotomy. Ann. Surg., 177:669, (cefazolin) being instituted: 1) 12 hours preoperatively; 1973. 2) just prior to operation; 3) just after operation; or 4) 12. Stone, H. H., and Kolb, L. D.: The Evolution and Spread of never. The placebo could be distinguished only by Gentamicin-Resistant Pseudomonads. J. Trauma, 11:586, 1971. 13. Winters, R. E., Litwack, K. D., and Hewitt, W. L.: Relation Be- breaking the numbered code. During operation, samples tween Dose and Levels of Gentamicin in Blood. J. Infect. Dis., ofperipheral and portal venous blood, visceral secretions, 124; Supplement: 590, 1971.