DIAG. MICROBIOL.INFECT. DIS. 1990;13:181-185
181
Ciprofloxacin as Single-Dose Antibiotic Prophylaxis in Colorectal Surgery Results of a Randomized, Double-Blind Trial Gfinter G6rtz, Jochen Boese-Landgraf, Werner Hopfenmfiller, Arne Rodloff, and Jochen Kotwas
INTRODUCTION Perioperative administration of antibiotics has proved to be an effective measure for infection prophylaxis in colon surgery and has thus become an established procedure in most centers (Keighly, 1982; Stamatakis et al., 1982; Thiede et al., 1985; Wilson and Strachan, 1985; G6rtz et al., 1987). However, the problem of the most effective type of prophylaxis continues to be controversial (Karran et al., 1988; Playforth et al., 1988). Elective colon surgery has become so standardized that the risk of infection associated with the intervention can be well assessed. This risk is determined mainly by the intraoperative dissemination of pathogens, among which gram-negative Enterobacteriaceae and anaerobic bacteroides play a leading role (Keighly, 1982; Wilson and Strachan, 1985; G6rtz et al., 1987; Playforth et al., 1988. The risk may also be increased by patient-related factors, such as age, nutritional status, size, and localization of the tumor or concomitant diseases and surgical factors, like extent and duration of the intervention From the Department of Surgery, Section for General, Vascular, and Thoracic Surgery (G.G., J.B.L.), Institute for Medical Data Processing and Statistics (W.H.), Institute for Medical Microbiology (A.R.), and the Pharmacy of Steglitz Medical Center, Free University of Berlin (J.K.), Hindenburgdamm, Berlin, FRG. Address reprint requests to: Dr. G. G6rtz, Free University of Berlin, Chirurgische Klinik and Poliklinik, Hindenburgdamm 30, 1000Berlin 45, FRG Received January 10, 1990; revised and accepted January 12, 1990. © 1990Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/90/$3.50
or additional surgical measures (Shrock et al., 1973; Alexander-Williams and Keighly, 1982; Herter and Colacchio, 1982; Keighly, 1982; Thiede et al., 1985; Playforth et al., 1988). In a prospective, randomized, double-blind trial, we compared the effectiveness of ciprofloxacin (CIP) and moxalactam (MOX) given as a single perioperative dose.
MATERIAL A N D METHODS One hundred twenty patients were included in the study and randomized into two groups of 60 patients each. One group received either MOX (known in Europe and Japan as latamoxef) (2 g), a third-generation broad-spectrum cephalosporin (manufacturer, Shionogi, Japan); the others received CIP (200 mg), a broad-spectrum fluoroquinolone (manufacturer, Bayer AG, Leverkusen, West Germany); both were administered as a short intravenous (IV) infusion during induction of anesthesia. CIP and MOX are effective against a similar range of pathogens, with low activity against enterococci. However, because CIP has only weak activity against anaerobic bacteria, all patients additionally received a short IV infusion of 500 mg metronidazole 2 hr prior to surgery. Other pre- and postoperative measures included whole gut lavage, a physiological saline solution on the day before surgery, and parenteral nutrition until the sixth postoperative day. Enrolled patients had to fulfill the following criteria to be included in the trial: 1. Give informed consent.
182
2. Under elective surgery with opening of the colon. 3. Receive no antibiotic therapy before or on the first day after the intervention. 4. Receive preoperative preparation and postoperative treatment according to the regimen commonly applied at our hospital. Exclusion criteria were 1. Intolerance or hypersensitivity to the study antibiotics. 2. Severe complications not associated with the antibiotic during the operation or in the early postoperative phase (3 days after surgery): acute myocardial infarction, lung embolism, suture line leak, technically induced postoperative bleeding. The goal of the study was to assess the effectiveness of antibiotic prophylaxis, including the occurrence of postoperative superficial and deep purulent w o u n d infections in the area of the operative w o u n d and drainage, peritonitis, and sepsis requiring opening of w o u n d s because they were associated with tissue inflammation due to swelling, erythema, and increased sensitivity to pain. The assessment was based on the clinical appearance; demonstration of pathogens was not required. All results of routinely performed laboratory tests were recorded, as well as the results of aerobic and anaerobic bacteriological examinations of cultures obtained because of infection. The clinical data were recorded by the attending physicians on standardized documentation sheets, which were processed by the Institute for Medical Statistics. Statistical analysis was done as follows: The parameter-free two-sample test for independent samples according to Mann-Whitney was used to test the steady parameters for group differences. Significance was assumed if p < 0.05. Contingency tables with chi-square tests were used to test qualitative parameters for group differences. The program furthermore calculated the statistical parameters according to a so-called Yates correction. In suitable cases of four-field tables, the program used Fisher's exact test. RESULTS
Of the 120 patients, 9 (six CIP and three MOX) were excluded from assessment because they did not fulfill the study criteria. Reasons for exclusion were exploratory laparotomy without opening of the colon in two patients and the necessity of immediate
G. G6rtz et al.
TABLE 1.
Underlying Diseases/Risk Factors: Perioperative Prophylaxis with CIP versus MOX Regimen
Disease/Risk Factor
MOX
CIP
Diabetes Hypertension COLD Liver cirrhosis Cachexia Obesity Arteriosclerosis Cortisone therapy Smoker Cardiac infarction (status post) Nephropathy Rheumatic disease
6 7 6 2 0 12 6 2 13 4 2 1
2 9 3 1 1 10 1 0 12 3 1 0
antibiotic therapy in six patients. The two study groups did not differ with respect to age, body weight, height, and sex distribution. The incidence of underlying diseases and risk factors was higher in the MOX group than in the CIP group. If the concurrence of several risk factors in one patient is considered, the number of patients with risk factors is identical in both groups (Table 1). Preparation for surgery is described in Table 2. The frequency distribution of diagnoses was nearly the same in both groups; carcinoma was the most frequent diagnosis (MOX = 40, CIP = 38), followed by colonic diverticulosis (mc < 5, CIP = 7), polyps (MOX = 3, CIP = 2), Crohn's disease (MOX = 3, CIP = 2), carcinoma relapse (MOX = 0, CIP = 4), and others (MOX = 6, CIP = 1). The types of interventions are detailed in Table 3.
TABLE 2.
Type of Preoperative Bowel Preparation: Perioperative Prophylaxis with CIP versus MOX Regimen
Preoperative irradiation No hyperalimentation Parenteral hyperalimentation Enteral hyperalimentation Bowel preparation No preparation Whole gut lavage Astronaut diet Liquid diet
MOX
CIP
4 52 5 0
13 52 1 1
2 44 16 22
3 43 10 21
183
Prophylaxis in Colorectal Surgery
TABLE 3.
TABLE 4.
Perioperative Prophylaxis with Ciprofloxacin versus Moxalactam
Bacteriology of W o u n d Infections after Colorectal Surgery
Regimen (no. infections)
Regimen Procedure
MOX
CIP
Right hemicolectomy Left hemicolectomy Transverse colon resection Sigmoid continuity resection Anterior rectum resection (Dixon) Rectum amputation Cecal pole resection Artificial anus repositioning Exploratory laparotomy Colotomy
15 2 1 12 10 7 1 1 4 4
9 6 1 9 16 10 1 0 2 0
Postoperative Course W o u n d healing was seen in 55 patients of the MOX group (96%) and in 50 patients of the CIP group (93%). W o u n d healing disturbances included one w o u n d infection and one seroma in the MOX group and four w o u n d infections in the CIP group. Anastomotic insufficiency occurred in four patients between the seventh and eighteenth postoperative day (MOX = 1, CIP = 3) but did not require surgical therapy in any of them. Among other postoperative complications, urinary tract infection (MOX = 3, CIP = 3) and pneumonia (MOX = 5, CIP = 1) were the most frequent. These patients received appropriate antibiotic therapy. Other reasons for antibiotic therapy were fever of u n k n o w n origin (MOX = 3, CIP = 1), sepsis (MOX = 1, CIP = 0), and local peritonitis (MOX = 0, CIP = 1). Either single-agent drugs or combinations of penicillins, quinolones, cephalosporins, and substances effective against anaerobic strains were used for antibiotic therapy. The distribution of individual and mean values for leukocytes, hemoglobin, thrombocytes, hematocrit, creatinine, SGPT, Quick, partial thromboplastin time, blood sugar, and total protein showed no differences b e t w e e n the two groups before surgery or on the second and eighth postoperative day. The mean period of postoperative hospitalization was 15 days in both groups (9-60 days). Five patients (MOX = 4, CIP = 1) died between day 13 and day 46. The deceased patients had a mean age of 70 years. In none of these patients was death related to surgically induced infections. Causes of death were lung embolism (two), liver coma (one), ileus (one), and pneumonia (one). The cause of death could be correlated with preoperatively existing risk factors in all five patients. The patient with ileus had a primarily nonresectable rectal tumor with extensive
MOX (1) CIP (4)
Result of Culture Enterococcus sp. E. coli Bacteroides group Enterococcus sp. Klebsiella sp. S. epidermidis
1 1 1 2 1 1
peritoneal metastases, and the patient with pneumonia suffered from severe chronic obstructive lung disease. The causative pathogens in the five postoperative w o u n d infections were determined in four cultures (Table 4). All isolated strains, with the exception of enterococci and Staphylococcus epidermidis, were susceptible to the antibiotics used. Factors predisposing to w o u n d infection were obesity (two), advanced tumor stage (one), additional operations (two), and suture line leak (one). Symptoms that might be interpreted as antibioticinduced side effects occurred in five patients in the further course of treatment: skin rash (MOX = 1, CIP = 1), diarrhea (MOX = 0, CIP = 2), nausea (MOX = 1, CIP = 0). Antibiotic-associated renal or liver insufficiency or granulocytopenia did not occur in any of the patients.
Statistical A s s e s s m e n t The two groups did not differ significantly with respect to the independent variables. Some of the contingency tables showed a tendency toward group differences, but these were never significant.
DISCUSSION Despite careful surgical techniques and strict perioperative hygiene, opening of the large intestine during colon surgery results in the inevitable dissemination of enteric pathogens that cause the high postoperative infection rate in this type of surgery (Playforth et al., 1988; Sauven et al., 1988). Aerobic/anaerobic mixed infections with Escherichia coli and Bacteroides sp. are mainly involved (G6rtz et al., 1987). A large number of studies on the possibilities of reducing postoperative infections in colonic surgery have been performed in the past (Alexander-Williams and Keighley, 1982; Herter and Colacchio, 1981; Keighley, 1982; Thiede et al., 1985; Wilson and Strachan 1985; Wilson et al., 1986; G6rtz
184
et al., 1987; Karran et al., 1988; Playforth et al., 1988). They have used three different approaches: selective germ reduction by oral antibiotics, systemic antibiotic prophylaxis, and mechanical bowel cleansing by whole gut lavage. In the present trial, the antibiotics were given in addition to the whole gut lavage as the standard of preoperative bowel preparation. The effectiveness of a systemic antibiotic prophylaxis was documented for a large number of broad-spectrum antibiotic agents (Mittermayer et al., 1982; Stamatakis et al., 1982; Thiede et al., 1985; Mendil and Sochting, 1987; Karran et al., 1988). Various studies have confirmed the superiority of moxalactam for the prophylaxis of infections (Morris et al., 1984; Thomas et al., 1985; G6rtz et al., 1987; Sauven et al., 1988). The clinical application of CIP has been confirmed for a wide range of indications, especially for the treatment of Gram-negative infections (Adam, 1987). No studies have been done on the prophylactic application of this substance in elective colonic surgery. An indicator of successful infection prophylaxis in elective colorectal surgery is a postoperative infection rate below 10% in the area of the operative w o u n d (Thiede et al., 1985; G6rtz et al., 1987; Playforth et al., 1988). This was achieved with both broad-spectrum antibiotic agents used in this study. The low incidence of side effects observed in this study may be attributed to the antibiotics used;
G. GOrtz et al.
however, it was not possible to definitely associate the side effects with the prophylactically applied antibiotic. Other investigators reported an increased incidence of postoperative bleeding after prophylactic application of certain beta-lactamases, particularly MOX (Morris et al., 1984). Antibioticassociated postoperative bleeding was not seen in any of the patients included in our study, nor did the analysis of Quick values and partial thromboplastic time reveal any changes attributable to effects of the perioperatively applied antibiotics. This is in agreement with other investigators, who report that neither disturbance of thrombocyte function nor effects on humoral blood clotting mechanisms are to be expected after single antibiotic application (Andrassy et al., 1983). The reduction of the postoperative w o u n d infection rate markedly shortens the time of hospitalization. The mean postoperative hospitalization time was only 15 days in both groups, whereas patients with w o u n d infection or suture line leak had to stay in the hospital for an average of 27 days. This not only increases the treatment costs by approximately $2000 and reduces a patient's income due to a longer disability but also impairs the patient's quality of life by prolonging the period of convalescence and the physical stress associated with surgery. Economic reasons, therefore, justify the single application of 200 mg CIP or 2 g MOX as perioperative prophylaxis.
REFERENCES Adam D (1987) Ciprofloxacin 1987; FAC 6-3. Alexander-Williams J, Keighley MRB 91982) Assessing the problem, preparing the patient, and minimizing the risks in rectal cancer surgery. World J Surg 6:510-516. Andrassy K, Koderisch J, Fritz S, Ritz E (1983) New betalactam antibiotics and hemorrhagic diathesis: comparison of moxalactam and cefotaxime. Clin Ther 6:34-42. G6rtz G, Haring R, Boese-Landgraf J, Rodloff AC, Hopfenmuller W (1987) Is the employment of new broad spectrum antibiotics for prophylactic purposes in colonic surgery justified? In Progress in Antimicrobial and Anticancer Chemotherapy, Proceedings of the 15th International Congress of Chemotherapy, July 19-24. Eds., B Bekarda and H-P Kuemmerle, pp 1455-1457. Herter FP, Colacchio TA (1982) The influence of antibiotics on infection and anastomotic recurrence after colon resection for cancer. World J Surg 6:188-194. Karran S, Finnis D, Sutton G, Gartell PC (1988) Shortcourse antibiotic prophylaxis is inferior to 24 hr (cover) in elective colorectal surgery. Sixth Mediterranean Congress of Chemotherapy, May 1988; Abstr 342, pp 22-27. Keighly, MRB (1982) Prevention and treatment of infection in colorectal surgery. World J Surg 6:312-320. Mendel V, Sochting E (1987) One-shot-prophylaxe in der elektiven Kolonchirurgie, kontrollierte randomisierte
Studie mit Cefotaxim bzw. Mezlocillin Munch Med Wschr 129:469-470. Mittermayer H, Gross C, Brucke P (1982) Prophylaxis with single-dose cefuroxime/metronidazole versus metronidazole alone in elective colo-rectal surgery. Res Clin Forum 5:109-119. Morris DL, Fabricius PJ, Ambrose NS, Scammel B, Burdon DW, Keighley MRB (1984) A high incidence of bleeding is observed in a trial to determine whether addition of metronidazole is needed with latamoxef for prophylaxis in colorectal surgery. J Hosp Infect 5:398-409. Playforth MJ, Smith GMR, Evans M, Pollock AV (1988) Antimicrobial bowel preparation: oral, parenteral, or both? Dis Colon Rectum 31;90-93. Sauven P, Playforth MJ, Smith GMR, Evans M, Pollock AV (1988) Single dose antibiotic prophylaxis of abdominal surgical wound infection: a trial of preoperative latamoxef against preoperative tetracycline lavage. J R Soc Med 79:137-141. Schrock TR, Deveney CW, Dunphy JE (1973) Factors contributing to leakage of colonic anastomoses. Ann Surg 177:513-518. Stamatakis JD, Binu PS, Strachan CJL (1982) Prevention of wound and intra-abdominal sepsis following left colorectal resection. Coloproc 4:222-225.
Prophylaxis in Colorectal Surgery
Thiede A, Jostarndt J, Hamelmann H (1985) Interpretation der Ergebnisse klinischer Studien fur die praktische Kolon- und Rektumchirurgie. Zentralol Chir 110:539557. Thomas WE, Cooper MJ, Holt A, Reeves D (1985) Lactamofex: single agent prophylaxis in colorectal surgery. J Antimicrob Chemother 16:121-128.
185
Wilson AJ, Strachan CJL (1985) Perioperative prevention of infection in abdominal surgery. Antibiot Chemother 33:30-58. Wilson SE, Russell RW, Lewis RT, Ton GT, Jemsek JG (1986) Multicenter comparative study of cefotetan vs moxalactam in the treatment of intra-abdominal infections. Infect Surg (suppl):29-34.
181
Ciprofloxacin as Single-Dose Antibiotic Prophylaxis in Colorectal Surgery Results of a Randomized, Double-Blind Trial Gfinter G6rtz, Jochen Boese-Landgraf, Werner Hopfenmfiller, Arne Rodloff, and Jochen Kotwas
INTRODUCTION Perioperative administration of antibiotics has proved to be an effective measure for infection prophylaxis in colon surgery and has thus become an established procedure in most centers (Keighly, 1982; Stamatakis et al., 1982; Thiede et al., 1985; Wilson and Strachan, 1985; G6rtz et al., 1987). However, the problem of the most effective type of prophylaxis continues to be controversial (Karran et al., 1988; Playforth et al., 1988). Elective colon surgery has become so standardized that the risk of infection associated with the intervention can be well assessed. This risk is determined mainly by the intraoperative dissemination of pathogens, among which gram-negative Enterobacteriaceae and anaerobic bacteroides play a leading role (Keighly, 1982; Wilson and Strachan, 1985; G6rtz et al., 1987; Playforth et al., 1988. The risk may also be increased by patient-related factors, such as age, nutritional status, size, and localization of the tumor or concomitant diseases and surgical factors, like extent and duration of the intervention From the Department of Surgery, Section for General, Vascular, and Thoracic Surgery (G.G., J.B.L.), Institute for Medical Data Processing and Statistics (W.H.), Institute for Medical Microbiology (A.R.), and the Pharmacy of Steglitz Medical Center, Free University of Berlin (J.K.), Hindenburgdamm, Berlin, FRG. Address reprint requests to: Dr. G. G6rtz, Free University of Berlin, Chirurgische Klinik and Poliklinik, Hindenburgdamm 30, 1000Berlin 45, FRG Received January 10, 1990; revised and accepted January 12, 1990. © 1990Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/90/$3.50
or additional surgical measures (Shrock et al., 1973; Alexander-Williams and Keighly, 1982; Herter and Colacchio, 1982; Keighly, 1982; Thiede et al., 1985; Playforth et al., 1988). In a prospective, randomized, double-blind trial, we compared the effectiveness of ciprofloxacin (CIP) and moxalactam (MOX) given as a single perioperative dose.
MATERIAL A N D METHODS One hundred twenty patients were included in the study and randomized into two groups of 60 patients each. One group received either MOX (known in Europe and Japan as latamoxef) (2 g), a third-generation broad-spectrum cephalosporin (manufacturer, Shionogi, Japan); the others received CIP (200 mg), a broad-spectrum fluoroquinolone (manufacturer, Bayer AG, Leverkusen, West Germany); both were administered as a short intravenous (IV) infusion during induction of anesthesia. CIP and MOX are effective against a similar range of pathogens, with low activity against enterococci. However, because CIP has only weak activity against anaerobic bacteria, all patients additionally received a short IV infusion of 500 mg metronidazole 2 hr prior to surgery. Other pre- and postoperative measures included whole gut lavage, a physiological saline solution on the day before surgery, and parenteral nutrition until the sixth postoperative day. Enrolled patients had to fulfill the following criteria to be included in the trial: 1. Give informed consent.
182
2. Under elective surgery with opening of the colon. 3. Receive no antibiotic therapy before or on the first day after the intervention. 4. Receive preoperative preparation and postoperative treatment according to the regimen commonly applied at our hospital. Exclusion criteria were 1. Intolerance or hypersensitivity to the study antibiotics. 2. Severe complications not associated with the antibiotic during the operation or in the early postoperative phase (3 days after surgery): acute myocardial infarction, lung embolism, suture line leak, technically induced postoperative bleeding. The goal of the study was to assess the effectiveness of antibiotic prophylaxis, including the occurrence of postoperative superficial and deep purulent w o u n d infections in the area of the operative w o u n d and drainage, peritonitis, and sepsis requiring opening of w o u n d s because they were associated with tissue inflammation due to swelling, erythema, and increased sensitivity to pain. The assessment was based on the clinical appearance; demonstration of pathogens was not required. All results of routinely performed laboratory tests were recorded, as well as the results of aerobic and anaerobic bacteriological examinations of cultures obtained because of infection. The clinical data were recorded by the attending physicians on standardized documentation sheets, which were processed by the Institute for Medical Statistics. Statistical analysis was done as follows: The parameter-free two-sample test for independent samples according to Mann-Whitney was used to test the steady parameters for group differences. Significance was assumed if p < 0.05. Contingency tables with chi-square tests were used to test qualitative parameters for group differences. The program furthermore calculated the statistical parameters according to a so-called Yates correction. In suitable cases of four-field tables, the program used Fisher's exact test. RESULTS
Of the 120 patients, 9 (six CIP and three MOX) were excluded from assessment because they did not fulfill the study criteria. Reasons for exclusion were exploratory laparotomy without opening of the colon in two patients and the necessity of immediate
G. G6rtz et al.
TABLE 1.
Underlying Diseases/Risk Factors: Perioperative Prophylaxis with CIP versus MOX Regimen
Disease/Risk Factor
MOX
CIP
Diabetes Hypertension COLD Liver cirrhosis Cachexia Obesity Arteriosclerosis Cortisone therapy Smoker Cardiac infarction (status post) Nephropathy Rheumatic disease
6 7 6 2 0 12 6 2 13 4 2 1
2 9 3 1 1 10 1 0 12 3 1 0
antibiotic therapy in six patients. The two study groups did not differ with respect to age, body weight, height, and sex distribution. The incidence of underlying diseases and risk factors was higher in the MOX group than in the CIP group. If the concurrence of several risk factors in one patient is considered, the number of patients with risk factors is identical in both groups (Table 1). Preparation for surgery is described in Table 2. The frequency distribution of diagnoses was nearly the same in both groups; carcinoma was the most frequent diagnosis (MOX = 40, CIP = 38), followed by colonic diverticulosis (mc < 5, CIP = 7), polyps (MOX = 3, CIP = 2), Crohn's disease (MOX = 3, CIP = 2), carcinoma relapse (MOX = 0, CIP = 4), and others (MOX = 6, CIP = 1). The types of interventions are detailed in Table 3.
TABLE 2.
Type of Preoperative Bowel Preparation: Perioperative Prophylaxis with CIP versus MOX Regimen
Preoperative irradiation No hyperalimentation Parenteral hyperalimentation Enteral hyperalimentation Bowel preparation No preparation Whole gut lavage Astronaut diet Liquid diet
MOX
CIP
4 52 5 0
13 52 1 1
2 44 16 22
3 43 10 21
183
Prophylaxis in Colorectal Surgery
TABLE 3.
TABLE 4.
Perioperative Prophylaxis with Ciprofloxacin versus Moxalactam
Bacteriology of W o u n d Infections after Colorectal Surgery
Regimen (no. infections)
Regimen Procedure
MOX
CIP
Right hemicolectomy Left hemicolectomy Transverse colon resection Sigmoid continuity resection Anterior rectum resection (Dixon) Rectum amputation Cecal pole resection Artificial anus repositioning Exploratory laparotomy Colotomy
15 2 1 12 10 7 1 1 4 4
9 6 1 9 16 10 1 0 2 0
Postoperative Course W o u n d healing was seen in 55 patients of the MOX group (96%) and in 50 patients of the CIP group (93%). W o u n d healing disturbances included one w o u n d infection and one seroma in the MOX group and four w o u n d infections in the CIP group. Anastomotic insufficiency occurred in four patients between the seventh and eighteenth postoperative day (MOX = 1, CIP = 3) but did not require surgical therapy in any of them. Among other postoperative complications, urinary tract infection (MOX = 3, CIP = 3) and pneumonia (MOX = 5, CIP = 1) were the most frequent. These patients received appropriate antibiotic therapy. Other reasons for antibiotic therapy were fever of u n k n o w n origin (MOX = 3, CIP = 1), sepsis (MOX = 1, CIP = 0), and local peritonitis (MOX = 0, CIP = 1). Either single-agent drugs or combinations of penicillins, quinolones, cephalosporins, and substances effective against anaerobic strains were used for antibiotic therapy. The distribution of individual and mean values for leukocytes, hemoglobin, thrombocytes, hematocrit, creatinine, SGPT, Quick, partial thromboplastin time, blood sugar, and total protein showed no differences b e t w e e n the two groups before surgery or on the second and eighth postoperative day. The mean period of postoperative hospitalization was 15 days in both groups (9-60 days). Five patients (MOX = 4, CIP = 1) died between day 13 and day 46. The deceased patients had a mean age of 70 years. In none of these patients was death related to surgically induced infections. Causes of death were lung embolism (two), liver coma (one), ileus (one), and pneumonia (one). The cause of death could be correlated with preoperatively existing risk factors in all five patients. The patient with ileus had a primarily nonresectable rectal tumor with extensive
MOX (1) CIP (4)
Result of Culture Enterococcus sp. E. coli Bacteroides group Enterococcus sp. Klebsiella sp. S. epidermidis
1 1 1 2 1 1
peritoneal metastases, and the patient with pneumonia suffered from severe chronic obstructive lung disease. The causative pathogens in the five postoperative w o u n d infections were determined in four cultures (Table 4). All isolated strains, with the exception of enterococci and Staphylococcus epidermidis, were susceptible to the antibiotics used. Factors predisposing to w o u n d infection were obesity (two), advanced tumor stage (one), additional operations (two), and suture line leak (one). Symptoms that might be interpreted as antibioticinduced side effects occurred in five patients in the further course of treatment: skin rash (MOX = 1, CIP = 1), diarrhea (MOX = 0, CIP = 2), nausea (MOX = 1, CIP = 0). Antibiotic-associated renal or liver insufficiency or granulocytopenia did not occur in any of the patients.
Statistical A s s e s s m e n t The two groups did not differ significantly with respect to the independent variables. Some of the contingency tables showed a tendency toward group differences, but these were never significant.
DISCUSSION Despite careful surgical techniques and strict perioperative hygiene, opening of the large intestine during colon surgery results in the inevitable dissemination of enteric pathogens that cause the high postoperative infection rate in this type of surgery (Playforth et al., 1988; Sauven et al., 1988). Aerobic/anaerobic mixed infections with Escherichia coli and Bacteroides sp. are mainly involved (G6rtz et al., 1987). A large number of studies on the possibilities of reducing postoperative infections in colonic surgery have been performed in the past (Alexander-Williams and Keighley, 1982; Herter and Colacchio, 1981; Keighley, 1982; Thiede et al., 1985; Wilson and Strachan 1985; Wilson et al., 1986; G6rtz
184
et al., 1987; Karran et al., 1988; Playforth et al., 1988). They have used three different approaches: selective germ reduction by oral antibiotics, systemic antibiotic prophylaxis, and mechanical bowel cleansing by whole gut lavage. In the present trial, the antibiotics were given in addition to the whole gut lavage as the standard of preoperative bowel preparation. The effectiveness of a systemic antibiotic prophylaxis was documented for a large number of broad-spectrum antibiotic agents (Mittermayer et al., 1982; Stamatakis et al., 1982; Thiede et al., 1985; Mendil and Sochting, 1987; Karran et al., 1988). Various studies have confirmed the superiority of moxalactam for the prophylaxis of infections (Morris et al., 1984; Thomas et al., 1985; G6rtz et al., 1987; Sauven et al., 1988). The clinical application of CIP has been confirmed for a wide range of indications, especially for the treatment of Gram-negative infections (Adam, 1987). No studies have been done on the prophylactic application of this substance in elective colonic surgery. An indicator of successful infection prophylaxis in elective colorectal surgery is a postoperative infection rate below 10% in the area of the operative w o u n d (Thiede et al., 1985; G6rtz et al., 1987; Playforth et al., 1988). This was achieved with both broad-spectrum antibiotic agents used in this study. The low incidence of side effects observed in this study may be attributed to the antibiotics used;
G. GOrtz et al.
however, it was not possible to definitely associate the side effects with the prophylactically applied antibiotic. Other investigators reported an increased incidence of postoperative bleeding after prophylactic application of certain beta-lactamases, particularly MOX (Morris et al., 1984). Antibioticassociated postoperative bleeding was not seen in any of the patients included in our study, nor did the analysis of Quick values and partial thromboplastic time reveal any changes attributable to effects of the perioperatively applied antibiotics. This is in agreement with other investigators, who report that neither disturbance of thrombocyte function nor effects on humoral blood clotting mechanisms are to be expected after single antibiotic application (Andrassy et al., 1983). The reduction of the postoperative w o u n d infection rate markedly shortens the time of hospitalization. The mean postoperative hospitalization time was only 15 days in both groups, whereas patients with w o u n d infection or suture line leak had to stay in the hospital for an average of 27 days. This not only increases the treatment costs by approximately $2000 and reduces a patient's income due to a longer disability but also impairs the patient's quality of life by prolonging the period of convalescence and the physical stress associated with surgery. Economic reasons, therefore, justify the single application of 200 mg CIP or 2 g MOX as perioperative prophylaxis.
REFERENCES Adam D (1987) Ciprofloxacin 1987; FAC 6-3. Alexander-Williams J, Keighley MRB 91982) Assessing the problem, preparing the patient, and minimizing the risks in rectal cancer surgery. World J Surg 6:510-516. Andrassy K, Koderisch J, Fritz S, Ritz E (1983) New betalactam antibiotics and hemorrhagic diathesis: comparison of moxalactam and cefotaxime. Clin Ther 6:34-42. G6rtz G, Haring R, Boese-Landgraf J, Rodloff AC, Hopfenmuller W (1987) Is the employment of new broad spectrum antibiotics for prophylactic purposes in colonic surgery justified? In Progress in Antimicrobial and Anticancer Chemotherapy, Proceedings of the 15th International Congress of Chemotherapy, July 19-24. Eds., B Bekarda and H-P Kuemmerle, pp 1455-1457. Herter FP, Colacchio TA (1982) The influence of antibiotics on infection and anastomotic recurrence after colon resection for cancer. World J Surg 6:188-194. Karran S, Finnis D, Sutton G, Gartell PC (1988) Shortcourse antibiotic prophylaxis is inferior to 24 hr (cover) in elective colorectal surgery. Sixth Mediterranean Congress of Chemotherapy, May 1988; Abstr 342, pp 22-27. Keighly, MRB (1982) Prevention and treatment of infection in colorectal surgery. World J Surg 6:312-320. Mendel V, Sochting E (1987) One-shot-prophylaxe in der elektiven Kolonchirurgie, kontrollierte randomisierte
Studie mit Cefotaxim bzw. Mezlocillin Munch Med Wschr 129:469-470. Mittermayer H, Gross C, Brucke P (1982) Prophylaxis with single-dose cefuroxime/metronidazole versus metronidazole alone in elective colo-rectal surgery. Res Clin Forum 5:109-119. Morris DL, Fabricius PJ, Ambrose NS, Scammel B, Burdon DW, Keighley MRB (1984) A high incidence of bleeding is observed in a trial to determine whether addition of metronidazole is needed with latamoxef for prophylaxis in colorectal surgery. J Hosp Infect 5:398-409. Playforth MJ, Smith GMR, Evans M, Pollock AV (1988) Antimicrobial bowel preparation: oral, parenteral, or both? Dis Colon Rectum 31;90-93. Sauven P, Playforth MJ, Smith GMR, Evans M, Pollock AV (1988) Single dose antibiotic prophylaxis of abdominal surgical wound infection: a trial of preoperative latamoxef against preoperative tetracycline lavage. J R Soc Med 79:137-141. Schrock TR, Deveney CW, Dunphy JE (1973) Factors contributing to leakage of colonic anastomoses. Ann Surg 177:513-518. Stamatakis JD, Binu PS, Strachan CJL (1982) Prevention of wound and intra-abdominal sepsis following left colorectal resection. Coloproc 4:222-225.
Prophylaxis in Colorectal Surgery
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