Prophylactic Antibiotics in Noncardiac Thoracic Operations Lester R. Bryant, M.D., Marcus L. Dillon, M.D., and Kazi Mobin-Uddin, M.D. ABSTRACT A high incidence of thoracotomy wound infection and empyema in 1972 was associated with inadequate and irregular administration of prophylactic antibiotics. Beginning with 1973, a strict regimen was adopted that combined systemic cephalosporins and two topical antibiotics (cephalothin and kanamycin). Emphasis was placed on preoperative administration of the systemic agent and on use of the topical drugs before the operative field was contaminated. The patient groups for 1972 and 1973 were similar in most respects, but the wound complication rate was 18.4%in 1972 and 4.8% in 1973.
W
hile thoracic surgeons have used antibiotics liberally to prevent postoperative infectious complications, they have not performed randomized and control studies that could form a basis for prophylactic antibiotic therapy. The current textbooks of thoracic surgery either provide little advice for antimicrobial prophylaxis or suggest its use without documentation. Therefore, it is not yet possible to find authoritative recommendations on this subject when it becomes necessary to evaluate the infection rate or antibiotic regimen of a thoracic surgical unit. In the last quarter of 1972 we became aware of an increasing frequency of postoperative wound infections and empyema in patients subjected to pulmonary resection and other noncardiac thoracic procedures. A delay in recognition of the problem was partly due to the dilutional effect of the larger volume of cardiovascular operations being performed by the same unit. An explanation for the increase in complications was not found despite a review of surgical techniques, operating room technology, and personnel changes. In reviewing preoperative management, however, it was noted that the patients undergoing cardiovascular operations received without fail the prophylactic antibiotics listed in the protocol used by the surgical house staff for preoperative and postoperative care. The drugs were started on the evening before operation and continued until the fifth postoperative day. By contrast, there appeared to be no pattern in the use of antimicrobial prophylaxis for those patients subjected to pulmonary resection or mediastinal procedures. Despite conflicting reports on the value of prophylactic antibiotics, we beFrom the Departments of Surgery, University of Kentucky Medical Center, Lexington, Ky., and Louisiana State University Medical Center, New Orleans, La. Presented at the Twenty-first Annual Meeting of the Southern Thoracic Surgical Association, Williamsburg, Va., Nov. 7-9, 1974. Address reprint requests to Dr. Bryant, Section of Thoracic and Cardiovascular Surgery, LSU Medical Center, 1542 Tulane Ave., New Orleans, La. 70112.
670
THE ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics lieved sufficient data had been accumulated from studies not involving thoracic procedures to warrant a limited trial [ 1 , 3 , 5 , 12,141. The results of that investigation form the basis of this report.
Materials and Methods With the exception of a few patients who died within the first seven postoperative days, this study includes all adults who underwent a major thoracotomy not requiring cardiopulmonary bypass or vascular reconstruction in 1972 and 1973. None of those who died early postoperatively had evidence of empyema or wound infection. For 1972, the 76 patients included 51 men and 25 women with an average age of 45.2 years (range, 16 to 86 years). In 1973, 53 men and 31 women comprised a total of 84 patients with an average age of 46.2 years (range, 16 to 84 years). Table 1 shows the postoperative diagnoses and Table 2 provides a comparison of the operative procedures performed during the two years. Pulmonary resections accounted for 67% of the operations in 1972 and 70% in 1973. When these are added to the decortications performed for empyema, the exploratory thoracotomies for bleeding due to penetrating trauma, and the tracheal and esophageal resections, 87% of the operations were classified as contaminated in 1972 and 83% in 1973. Lateral thoracotomy or median sternotomy incisions were used according to the planned intrathoracic procedure, and the pleural cavity or mediastinum was drained with one or more large chest tubes (32 to 360 brought through stab wounds at least 6 cm from the operative incision. Twenty-two-gauge steel wires were used for sternal reapproximation, doubled No. 1 chromic catgut was utilized TABLE 1 . PRIMARY DIAGNOSES IN PATIENTS WHO UNDERWENT THORACOTOMY IN 1972 AND 1973
Diagnosis
1972
Bronchogenic carcinoma Carcinoma metastatic to the lungs Bronchiectasis Granuloma of the lung (inactive) Recurrent pneumothorax Tuberculosis Chronic pneumonitis Cavitary histoplasmosis Bullous emphysema Miscellaneous pulmonary parenchymal lesions Postpneumonic empyema Penetrating thoracic trauma Tracheal or esophageal obstruction Constrictive pericarditis Mediastinal neoplasms Hiatus hernia or achalasia Total
15 5 3 8 5 2 2 3 5 5 8 4 1 0 5 5 76
No. of Patients 1973
16 6 6 12 5 5 7 0 0 5 3 2 3 5
7
2 84
VOL. 19, NO. 6, JUNE, 1975
671
BRYANT ET AL. TABLE 2. COMPARISON OF OPERATIONS PERFORMED IN 1972 AND 1973
Operation
1972
Pneumonectomy Lobectomy Segmental resection Pulmonary wedge resection Decortication Exploratory thoracotomy Esophageal resection Miscellaneous procedures Total
6 20 2 23 8 7 3 7 76
No. of Patients 1973
6 25 2 26 3 8 2 12 84
for pericostal sutures, and polyglycolic acid or chromic catgut sutures were used in the approximation of soft tissues. A majority of the patients who had pulmonary resection in 1972 and all but 4 in 1973 had preoperative bacteriological sputum cultures. The cultures showed only Neisseria species and diphtheroids in nearly one-third of the patients in each year. Several potential pathogens were isolated from the sputum of the remainder, but no single organism predominated. Preoperative and intraoperative bacterial cultures were made on the pleural exudate of all patients who had decortication. Five of the 8 patients in 1972 had no organisms isolated, 2 patients showed Pseudomonas aerugtnosa, and 1 had Diplococcus jmeumoniae. In 1973 the pleural exudate of 1 patient grew Klebsiellapneumoniae, 1 had Escherichia coli, and the third had no organisms isolated. During 1972, 35 of the 76 patients received antibiotics to prevent postoperative infection. The agents administered included ampicillin, penicillin, methicillin, carbenicillin, tetracycline, gentamicin, and cephalothin, selected on the basis of sensitivity of the organisms isolated when possible. Eleven patients received at least one dose of the antibacterial drug before operation, but the remaining 24 patients were not given their antibiotic until they were transferred to the recovery room following operation. Beginning on January 1 , 1973, the following regimen of antibiotic prophylaxis was started: Preoperative: ( 1 ) cephalexin, 0.5 gm by mouth the evening before operation; and (2) cephalothin, 1.0 gm intramuscularly or intravenously on call to the operating room Postoperative: ( 1) cephalothin, 1 gm intramuscularly or intravenously every six hours for two days, followed by (2) cephalexin, 0.25 gm by mouth four times daily for three days.
Two patients who required emergency thoracotomy for gunshot wounds did not receive cephalexin before operation, and cephalothin was continued intraven-
672
T H E ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics ously through the fifth postoperative day in patients who had esophageal procedures. During both years, the pleural cavity and operative incision were irrigated with at least 1 liter of saline at the end of the definitive procedure. In a few patients in 1972 the pleural cavity and incision were irrigated with a solution of 1 gm of kanamycin or 1 gm of cephalothin in a liter of saline just before wound closure. Starting with January, 1973, a routine for topical antibiotic application was initiated with the use of both cephalothin and kanamycin solutions for each operation. Arbitrarily, each solution contained 1gm of the drug in 1 liter of saline. Using aseptic type syringes for application, each solution was liberally applied to the layers of the incision and to the operative field before the definitive intrathoracic procedure was started, approximately midway through the operation, and just before wound closure. Wound infection was defined as suppuration in the operative incision whether it drained spontaneously or required reopening of the incision because of unequivocal erythema and induration. Empyema was considered to be present when purulent material was drained from the pleural cavity.
Results During 1972,8 of the 76 patients developed a postoperative wound infection, 5 had postoperative empyema, and 1 had both empyema and a wound infection. This constituted a complication rate of 18.4%. One of the 14 patients had had a median sternotomy, while the remainder had undergone either a posterolateral thoracotomy or an anterolateral incision. The antibiotics were started preoperatively in 2 of the 9 patients with a wound infection and 4 of the 6 who developed empyema. S . aureuS was isolated from wound cultures in 4 of the 9 patients. The organisms had differing sensitivity patterns, however, and the infections due to this agent occurred over an eight-month interval. Although no organism was isolated, two infections were thought to be due to anaerobes because of the odor of the wound drainage. Klebsiella peumoniae, E . coli, and P . aeruginosa were cultured from the remaining infected incisions. Two of the 6 patients with postoperative empyema hadS. aurew in the pleural exudate, 1 had Protew mirabilis, and 1 had E . coli. In 2 instances the empyema was a recurrence after decortication, with P . aemginosa as the etiological agent. Only 1of these 6 patients had a persistent air leak following operation (right lower lobectomy), but a leak from the bronchus developed after empyema was well established in a patient who had undergone left pneumonectomy. This patient was the only one of the 1972 group who eventually died as a direct result of the postoperative infection. N o single factor or constellation of factors could be identified as the primary cause of infection in the 14 patients. Operations on the respiratory and gastrointestinal tracts are known to have an increased infection rate, however, and 6 of the 9 patients with wound infection had clean-contaminated operations 171. Similarly,
VOL. 19, NO. 6, JUNE, 1975
673
BRYANT ET AL. the operative procedures were classified as clean-contaminated for 4 of the 6 patients with postoperative empyema. For 1 patient with wound infection and for both of those with recurrent empyema the operations were classified as dirty. During 1973 there were only 2 instances each of postoperative wound infection and empyema among the 84 patients who underwent thoracotomy. This complication rate of 4.8% was in pleasant contrast to the results in 1972. A resistant S. aureus was responsible for a median sternotomy wound infection and the subsequent death of a patient who had tracheal reconstruction for stenosis. The other wound infection was due to P. aeruginosa in a patient who underwent decortication for chronic empyema. By definition, the operations in both these patients were classified as dirty. One of the 2 patients with postoperative empyema in 1973 had an air leak for fifteen days following right lower lobectomy. An E. coli sensitive to cephalothin was isolated from the purulent drainage that appeared eight days after operation and three days after cephalexin had been discontinued. The other patient had empyema necessitatis that appeared nearly four months after pneumonectomy. N o organism could be identified from cultures and no bronchial leak was demonstrated. Each of these operations was classified as clean-contaminated.
Comment We do not advocate routine use of prophylactic antibiotics for patients who require thoracic operations. In addition, we make no general claim that this study documents a lower postoperative infection rate than might be achieved without antibiotics under other circumstances. This report does, however, describe a regimen of antibiotic prophylaxis that eliminated a completely intolerable rate of postoperative wound infection in one institution. The regimen adopted is a vigorous program incorporating both systemic and topical antibiotics. This dual coverage was inspired partly by an urgent need to decrease the postoperative complications and also by multiple studies that attested to the effectiveness of topical antibiotics in reducing the incidence of wound infection [ l , 1 1 , 15, 161. There has been controversy over the value of prophylactic antibiotics from two standpoints. The first is the general question of whether the risk of sensitization and the development of resistant bacterial strains warrant antibiotic administration for a theoretical benefit. Second, there have been conflicting reports about the ability of antibiotics to reduce postoperative infection rates [ l , 9, 141. Unequivocal evidence in laboratory animals has shown that wound infection can be prevented or sharply reduced by administration of antibiotics to which the contaminating organism is sensitive [ l , 161. The experimental work of Miles and associates [ 121 and of Burke [5] established the importance of antibiotic administration prior to contamination for effective prophylaxis. In clinical studies with antimicrobials, Bernard and Cole [3] and Polk and Lopez-Mayor [14] showed a significant reduction in wound infection and in intraabdominal sepsis after operations on the biliary and gastrointestinal tracts. The patients in their investigations 674
THE ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics received the drugs shortly before operation, during the operative procedure [31, and during the early hours after operation. Antibiotics were not continued into the first postoperative days. These workers suggested that the failure of antimicrobial prophylaxis in previous studies was due to faulty comparison of patient groups and to failure to administer the drugs until after bacterial contamination had occurred. Additional clinical studies using cephalosporins have further confirmed the efficacy of prophylactic antibioticsin reducing postoperative infectious complications [6, 8, 101. Admittedly, the studies of antibiotic prophylaxis for abdominal operations have an unknown applicability to thoracic surgical procedures. There are obvious anatomical differences in the two regions and disparate bacterial flora in the respiratory and gastrointestinal tracts. Unfortunately, we have not found reports that included comparison of antibiotic prophylaxis for patients subjected to thoracic and abdominal procedures. In a study with dogs, Bhayana and co-workers [4] did pulmonary resections and contaminated the pleural cavity with known bacteria. They compared saline irrigation of the pleural cavity with topical penicillin and streptomycin and with systemic antibiotics given after the resection. All animals receiving only saline irrigation died, but 70% of those having a single topical irrigation of pencillin and streptomycin survived. Systemic antibiotics combined with topical irrigation resulted in 100%survival. Other studies to support the use of topical antibioticshave been reported [ 13, 161, but irrigation of the operative field and wound edges with the chosen solution has generally been done just before wound closure. Application of the antibiotic solution at the start of the definitive procedure and during the course of dissection is more in keeping with the principles of antibiotic use discussed previously. If a systemic antibiotic has been administered preoperatively, a measurable level should be present in the tissue when the operative procedure is begun. As dissection and exposure proceed, however, drying of tissue surfaces, use of the electrocautery, and ligation of bleeding points may produce tissue fragments that are isolated from the blood supply and the circulating antibiotic. If the operative field becomes contaminated as part of a planned bronchopulmonary o r esophageal resection or by accident, the devitalized tissues should form the most likely nidus for infection. In relatively long operations, dried tissue fluids and fibrin or sequestration of contaminated materials in tissue planes may reduce the opportunity for a topical antibiotic to be effective if applied only at the end of the procedure. In this investigation cephalothin and cephalexin were chosen as the systemic prophylactic antibiotics because several reports have confirmed the effectiveness of the cephalosporins [2,6, 10, 141. The selection of cephalothin and kanamycin for topical application provided theoretical protection against the widest spectrum of bacteria usually associated with wound infections; P . aeruginosa is an exception. As stated earlier, it is not our wish to promote unnecessary use of antibiotics in circumstances in which need has not been demonstrated. For thoracic operations that do not involve a major pulmonary resection or an opening into the
VOL. 19, NO. 6, JUNE. 1975
675
BRYANT ET AL. esophagus, the use of antibiotics is questionable. Whether prophylaxis should be used with small procedures such as lung biopsy or wedge resection depends on the presence of pulmonary infection and the estimated opportunity for contamination of the operative field. The experience reported here is based on a patient population largely derived from the lower economic strata and for whom the great majority of operations were performed by the resident staff. Factors of this type may or may not have an effect on the wound complication rate at any one institution, but almost certainly they affect any comparison between institutions. Continuing experience with the antibiotic regimen has been very satisfactory and it is our intent to develop this program into a randomized study. The results observed from an initial experience of several years should contribute to the design of that study.
References 1 . Alexander, J. W., McGloin, J. J., and Altemeier, W. A. Penicillin prophylaxis in experimental wound infections. Surg Forum 1 1 :299, 1960. 2. Allen, J. L., Rampone, J. F., and Wheeless, C. R. Use of a prophylactic antibiotic in elective major gynecologic operations. Obstet Gynecol 39:2 18, 1972. 3. Bernard, H. R., and Cole, W. R. The prophylaxis of surgical infection: The effect of prophylactic antimicrobial drugs on the incidence of infection following potentially contaminated operations. Surgery 56: 15 1, 1964. 4. Bhayana, J. N., Gillespie, J. F., Nolan, J., and Ashburn, F. S. Prophylactic antibiotics in thoracic surgery. J Thorac Cardiouasc Surg 50:863, 1965. 5. Burke, J. F. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50: 16 1, 196 1. 6. Chetlin, S. H., and Elliot, D. H. Preoperative antibiotics in biliary surgery. Arch Surg 107:319, 1973. 7. Cruse, P. J., and Foord, R. A five year prospective study of 23,649 surgical wounds. Arch Surg 107206, 1973. 8 . Gibbs, R. S., DeCherney, A. H., and Schwarz, R. H. Prophylactic antibiotics in cesarean section. Am J Obstet Gynecol 114: 1048, 1972. 9. Karl, R. C., Mertz, J. J., Veith, F. J., and Dineen, P. Ineffectiveness of prophylactic antimicrobial drugs in surgery. N Engl J Med 275:305, 1966. 10. Ledger, W. J., Sweet, R. L., and Headington, J. T. The prophylactic use of cephaloridine in the prevention of pelvic infections in premenopausal women undergoing vaginal hysterectomy. Am J Obstet Gynecol 115:766, 1963. 1 1 . Matsumoto, T., Hardaway, R. M., Dobek, A. S., and Noyes, H. E. Antibiotic topical spray applied in a simulated combat wound. Arch Surg 95:288, 1967. 12. Miles, A. A., Miles, E. M., and Burke, J. The value and duration of defense reactions of the skin to the primary lodgement of bacteria. B r J Exp Pathol 38:79, 1957. 13. Nash, A. G., and Hugh, T. B. Topical ampicillin and wound infection in colon surgery. Br Med J 1:471, 1967. 14. Polk, H. C., Jr., and Lopez-Mayor, J. F. Postoperative wound infection: A prospective study of determinant factors and prevention. Surgery 66:97, 1969. 15. Seidenstein, M., Salomons, M. M., Herbsman, H., and Shaften, G. W. Evaluation of local antibiotic instillation in extremity wounds. Surgery 68:809, 1970. 16. Waterman, N. G., Howell, R. S., and Babrich, M. The effect of a prophylactic topical antibiotic (cephalothin) on the incidence of wound infection. Arch Surg 97:365, 1968.
676
T H E ANNALS OF THORACIC SURGERY
W
hile thoracic surgeons have used antibiotics liberally to prevent postoperative infectious complications, they have not performed randomized and control studies that could form a basis for prophylactic antibiotic therapy. The current textbooks of thoracic surgery either provide little advice for antimicrobial prophylaxis or suggest its use without documentation. Therefore, it is not yet possible to find authoritative recommendations on this subject when it becomes necessary to evaluate the infection rate or antibiotic regimen of a thoracic surgical unit. In the last quarter of 1972 we became aware of an increasing frequency of postoperative wound infections and empyema in patients subjected to pulmonary resection and other noncardiac thoracic procedures. A delay in recognition of the problem was partly due to the dilutional effect of the larger volume of cardiovascular operations being performed by the same unit. An explanation for the increase in complications was not found despite a review of surgical techniques, operating room technology, and personnel changes. In reviewing preoperative management, however, it was noted that the patients undergoing cardiovascular operations received without fail the prophylactic antibiotics listed in the protocol used by the surgical house staff for preoperative and postoperative care. The drugs were started on the evening before operation and continued until the fifth postoperative day. By contrast, there appeared to be no pattern in the use of antimicrobial prophylaxis for those patients subjected to pulmonary resection or mediastinal procedures. Despite conflicting reports on the value of prophylactic antibiotics, we beFrom the Departments of Surgery, University of Kentucky Medical Center, Lexington, Ky., and Louisiana State University Medical Center, New Orleans, La. Presented at the Twenty-first Annual Meeting of the Southern Thoracic Surgical Association, Williamsburg, Va., Nov. 7-9, 1974. Address reprint requests to Dr. Bryant, Section of Thoracic and Cardiovascular Surgery, LSU Medical Center, 1542 Tulane Ave., New Orleans, La. 70112.
670
THE ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics lieved sufficient data had been accumulated from studies not involving thoracic procedures to warrant a limited trial [ 1 , 3 , 5 , 12,141. The results of that investigation form the basis of this report.
Materials and Methods With the exception of a few patients who died within the first seven postoperative days, this study includes all adults who underwent a major thoracotomy not requiring cardiopulmonary bypass or vascular reconstruction in 1972 and 1973. None of those who died early postoperatively had evidence of empyema or wound infection. For 1972, the 76 patients included 51 men and 25 women with an average age of 45.2 years (range, 16 to 86 years). In 1973, 53 men and 31 women comprised a total of 84 patients with an average age of 46.2 years (range, 16 to 84 years). Table 1 shows the postoperative diagnoses and Table 2 provides a comparison of the operative procedures performed during the two years. Pulmonary resections accounted for 67% of the operations in 1972 and 70% in 1973. When these are added to the decortications performed for empyema, the exploratory thoracotomies for bleeding due to penetrating trauma, and the tracheal and esophageal resections, 87% of the operations were classified as contaminated in 1972 and 83% in 1973. Lateral thoracotomy or median sternotomy incisions were used according to the planned intrathoracic procedure, and the pleural cavity or mediastinum was drained with one or more large chest tubes (32 to 360 brought through stab wounds at least 6 cm from the operative incision. Twenty-two-gauge steel wires were used for sternal reapproximation, doubled No. 1 chromic catgut was utilized TABLE 1 . PRIMARY DIAGNOSES IN PATIENTS WHO UNDERWENT THORACOTOMY IN 1972 AND 1973
Diagnosis
1972
Bronchogenic carcinoma Carcinoma metastatic to the lungs Bronchiectasis Granuloma of the lung (inactive) Recurrent pneumothorax Tuberculosis Chronic pneumonitis Cavitary histoplasmosis Bullous emphysema Miscellaneous pulmonary parenchymal lesions Postpneumonic empyema Penetrating thoracic trauma Tracheal or esophageal obstruction Constrictive pericarditis Mediastinal neoplasms Hiatus hernia or achalasia Total
15 5 3 8 5 2 2 3 5 5 8 4 1 0 5 5 76
No. of Patients 1973
16 6 6 12 5 5 7 0 0 5 3 2 3 5
7
2 84
VOL. 19, NO. 6, JUNE, 1975
671
BRYANT ET AL. TABLE 2. COMPARISON OF OPERATIONS PERFORMED IN 1972 AND 1973
Operation
1972
Pneumonectomy Lobectomy Segmental resection Pulmonary wedge resection Decortication Exploratory thoracotomy Esophageal resection Miscellaneous procedures Total
6 20 2 23 8 7 3 7 76
No. of Patients 1973
6 25 2 26 3 8 2 12 84
for pericostal sutures, and polyglycolic acid or chromic catgut sutures were used in the approximation of soft tissues. A majority of the patients who had pulmonary resection in 1972 and all but 4 in 1973 had preoperative bacteriological sputum cultures. The cultures showed only Neisseria species and diphtheroids in nearly one-third of the patients in each year. Several potential pathogens were isolated from the sputum of the remainder, but no single organism predominated. Preoperative and intraoperative bacterial cultures were made on the pleural exudate of all patients who had decortication. Five of the 8 patients in 1972 had no organisms isolated, 2 patients showed Pseudomonas aerugtnosa, and 1 had Diplococcus jmeumoniae. In 1973 the pleural exudate of 1 patient grew Klebsiellapneumoniae, 1 had Escherichia coli, and the third had no organisms isolated. During 1972, 35 of the 76 patients received antibiotics to prevent postoperative infection. The agents administered included ampicillin, penicillin, methicillin, carbenicillin, tetracycline, gentamicin, and cephalothin, selected on the basis of sensitivity of the organisms isolated when possible. Eleven patients received at least one dose of the antibacterial drug before operation, but the remaining 24 patients were not given their antibiotic until they were transferred to the recovery room following operation. Beginning on January 1 , 1973, the following regimen of antibiotic prophylaxis was started: Preoperative: ( 1 ) cephalexin, 0.5 gm by mouth the evening before operation; and (2) cephalothin, 1.0 gm intramuscularly or intravenously on call to the operating room Postoperative: ( 1) cephalothin, 1 gm intramuscularly or intravenously every six hours for two days, followed by (2) cephalexin, 0.25 gm by mouth four times daily for three days.
Two patients who required emergency thoracotomy for gunshot wounds did not receive cephalexin before operation, and cephalothin was continued intraven-
672
T H E ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics ously through the fifth postoperative day in patients who had esophageal procedures. During both years, the pleural cavity and operative incision were irrigated with at least 1 liter of saline at the end of the definitive procedure. In a few patients in 1972 the pleural cavity and incision were irrigated with a solution of 1 gm of kanamycin or 1 gm of cephalothin in a liter of saline just before wound closure. Starting with January, 1973, a routine for topical antibiotic application was initiated with the use of both cephalothin and kanamycin solutions for each operation. Arbitrarily, each solution contained 1gm of the drug in 1 liter of saline. Using aseptic type syringes for application, each solution was liberally applied to the layers of the incision and to the operative field before the definitive intrathoracic procedure was started, approximately midway through the operation, and just before wound closure. Wound infection was defined as suppuration in the operative incision whether it drained spontaneously or required reopening of the incision because of unequivocal erythema and induration. Empyema was considered to be present when purulent material was drained from the pleural cavity.
Results During 1972,8 of the 76 patients developed a postoperative wound infection, 5 had postoperative empyema, and 1 had both empyema and a wound infection. This constituted a complication rate of 18.4%. One of the 14 patients had had a median sternotomy, while the remainder had undergone either a posterolateral thoracotomy or an anterolateral incision. The antibiotics were started preoperatively in 2 of the 9 patients with a wound infection and 4 of the 6 who developed empyema. S . aureuS was isolated from wound cultures in 4 of the 9 patients. The organisms had differing sensitivity patterns, however, and the infections due to this agent occurred over an eight-month interval. Although no organism was isolated, two infections were thought to be due to anaerobes because of the odor of the wound drainage. Klebsiella peumoniae, E . coli, and P . aeruginosa were cultured from the remaining infected incisions. Two of the 6 patients with postoperative empyema hadS. aurew in the pleural exudate, 1 had Protew mirabilis, and 1 had E . coli. In 2 instances the empyema was a recurrence after decortication, with P . aemginosa as the etiological agent. Only 1of these 6 patients had a persistent air leak following operation (right lower lobectomy), but a leak from the bronchus developed after empyema was well established in a patient who had undergone left pneumonectomy. This patient was the only one of the 1972 group who eventually died as a direct result of the postoperative infection. N o single factor or constellation of factors could be identified as the primary cause of infection in the 14 patients. Operations on the respiratory and gastrointestinal tracts are known to have an increased infection rate, however, and 6 of the 9 patients with wound infection had clean-contaminated operations 171. Similarly,
VOL. 19, NO. 6, JUNE, 1975
673
BRYANT ET AL. the operative procedures were classified as clean-contaminated for 4 of the 6 patients with postoperative empyema. For 1 patient with wound infection and for both of those with recurrent empyema the operations were classified as dirty. During 1973 there were only 2 instances each of postoperative wound infection and empyema among the 84 patients who underwent thoracotomy. This complication rate of 4.8% was in pleasant contrast to the results in 1972. A resistant S. aureus was responsible for a median sternotomy wound infection and the subsequent death of a patient who had tracheal reconstruction for stenosis. The other wound infection was due to P. aeruginosa in a patient who underwent decortication for chronic empyema. By definition, the operations in both these patients were classified as dirty. One of the 2 patients with postoperative empyema in 1973 had an air leak for fifteen days following right lower lobectomy. An E. coli sensitive to cephalothin was isolated from the purulent drainage that appeared eight days after operation and three days after cephalexin had been discontinued. The other patient had empyema necessitatis that appeared nearly four months after pneumonectomy. N o organism could be identified from cultures and no bronchial leak was demonstrated. Each of these operations was classified as clean-contaminated.
Comment We do not advocate routine use of prophylactic antibiotics for patients who require thoracic operations. In addition, we make no general claim that this study documents a lower postoperative infection rate than might be achieved without antibiotics under other circumstances. This report does, however, describe a regimen of antibiotic prophylaxis that eliminated a completely intolerable rate of postoperative wound infection in one institution. The regimen adopted is a vigorous program incorporating both systemic and topical antibiotics. This dual coverage was inspired partly by an urgent need to decrease the postoperative complications and also by multiple studies that attested to the effectiveness of topical antibiotics in reducing the incidence of wound infection [ l , 1 1 , 15, 161. There has been controversy over the value of prophylactic antibiotics from two standpoints. The first is the general question of whether the risk of sensitization and the development of resistant bacterial strains warrant antibiotic administration for a theoretical benefit. Second, there have been conflicting reports about the ability of antibiotics to reduce postoperative infection rates [ l , 9, 141. Unequivocal evidence in laboratory animals has shown that wound infection can be prevented or sharply reduced by administration of antibiotics to which the contaminating organism is sensitive [ l , 161. The experimental work of Miles and associates [ 121 and of Burke [5] established the importance of antibiotic administration prior to contamination for effective prophylaxis. In clinical studies with antimicrobials, Bernard and Cole [3] and Polk and Lopez-Mayor [14] showed a significant reduction in wound infection and in intraabdominal sepsis after operations on the biliary and gastrointestinal tracts. The patients in their investigations 674
THE ANNALS OF THORACIC SURGERY
Prophylactic Antibiotics received the drugs shortly before operation, during the operative procedure [31, and during the early hours after operation. Antibiotics were not continued into the first postoperative days. These workers suggested that the failure of antimicrobial prophylaxis in previous studies was due to faulty comparison of patient groups and to failure to administer the drugs until after bacterial contamination had occurred. Additional clinical studies using cephalosporins have further confirmed the efficacy of prophylactic antibioticsin reducing postoperative infectious complications [6, 8, 101. Admittedly, the studies of antibiotic prophylaxis for abdominal operations have an unknown applicability to thoracic surgical procedures. There are obvious anatomical differences in the two regions and disparate bacterial flora in the respiratory and gastrointestinal tracts. Unfortunately, we have not found reports that included comparison of antibiotic prophylaxis for patients subjected to thoracic and abdominal procedures. In a study with dogs, Bhayana and co-workers [4] did pulmonary resections and contaminated the pleural cavity with known bacteria. They compared saline irrigation of the pleural cavity with topical penicillin and streptomycin and with systemic antibiotics given after the resection. All animals receiving only saline irrigation died, but 70% of those having a single topical irrigation of pencillin and streptomycin survived. Systemic antibiotics combined with topical irrigation resulted in 100%survival. Other studies to support the use of topical antibioticshave been reported [ 13, 161, but irrigation of the operative field and wound edges with the chosen solution has generally been done just before wound closure. Application of the antibiotic solution at the start of the definitive procedure and during the course of dissection is more in keeping with the principles of antibiotic use discussed previously. If a systemic antibiotic has been administered preoperatively, a measurable level should be present in the tissue when the operative procedure is begun. As dissection and exposure proceed, however, drying of tissue surfaces, use of the electrocautery, and ligation of bleeding points may produce tissue fragments that are isolated from the blood supply and the circulating antibiotic. If the operative field becomes contaminated as part of a planned bronchopulmonary o r esophageal resection or by accident, the devitalized tissues should form the most likely nidus for infection. In relatively long operations, dried tissue fluids and fibrin or sequestration of contaminated materials in tissue planes may reduce the opportunity for a topical antibiotic to be effective if applied only at the end of the procedure. In this investigation cephalothin and cephalexin were chosen as the systemic prophylactic antibiotics because several reports have confirmed the effectiveness of the cephalosporins [2,6, 10, 141. The selection of cephalothin and kanamycin for topical application provided theoretical protection against the widest spectrum of bacteria usually associated with wound infections; P . aeruginosa is an exception. As stated earlier, it is not our wish to promote unnecessary use of antibiotics in circumstances in which need has not been demonstrated. For thoracic operations that do not involve a major pulmonary resection or an opening into the
VOL. 19, NO. 6, JUNE. 1975
675
BRYANT ET AL. esophagus, the use of antibiotics is questionable. Whether prophylaxis should be used with small procedures such as lung biopsy or wedge resection depends on the presence of pulmonary infection and the estimated opportunity for contamination of the operative field. The experience reported here is based on a patient population largely derived from the lower economic strata and for whom the great majority of operations were performed by the resident staff. Factors of this type may or may not have an effect on the wound complication rate at any one institution, but almost certainly they affect any comparison between institutions. Continuing experience with the antibiotic regimen has been very satisfactory and it is our intent to develop this program into a randomized study. The results observed from an initial experience of several years should contribute to the design of that study.
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