Paper Eur Surg Res 1989;21(suppl 1):14-18 Ceftriaxone Single Dose versus Ceftazidime Multiple Doses in the Prophylaxis of Infection in Colorectal Surgery J.P. J. Palla Consiglieri Garcia Pedroso Santa Marta Hospital (Hospitais Civis de Lisboa), Department of Surgery, Lisbon, Portugal Key Words Infection prophylaxis Colorectal surgery Ceftriaxone Ceftazidime Abstract Sixty patients admitted to the hospital for colorectal surgery were randomly assigned to prophylaxis either with a ® single dose of ceftriaxone (Rocephin ) i.v. plus metronidazole given 30 min prior to induction of anesthesia or with multiple doses of ceftazidime plus metronidazole given repeatedly every 8 h up to 24 h after surgery. The overall number of infections observed with the long-acting cephalosporin ceftriaxone was 4 (2 local and 2 remote), with the short-acting ceftazidime the number was 9 (5 local and 4 remote). Neither regimen was associated with adverse reactions. Dr. Palla Garcia, R. Rua Luciano Cordeiro 92-R/C, 1100 Lisboa (Portugal) Introduction Since the beginnings of colorectal surgery, infection has been a very frequent and disturbing complication, provoked by endogenous bacteria, aerobes and anaerobes from the colon lumen. Thus, a number of measures must be taken to avoid bacterial contamination. Of utmost importance is the complete removal of fecal material from the colon lumen prior to surgery (colic washout), if at all possible. Meticulous surgical technique including careful hemostasis, avoidance of tissue destruction or ischemia, use of fine sutures, and closed drainage of dead spaces are, naturally, prerequisites for the prevention of infections. Risk factors for infection, related to the patient’s condition, such as nutritional and immunologic status or the presence of remote infections that may adversely influence the postoperative course also have to be considered . Colic washout and colic sterilization with nonabsorbable sulfonamides were the measures taken by Garlock and Sealey  as early as 1939 to prevent infections. Oral antibiotics that destroy the normal colic flora were much used later in the prophylaxis of infection associated with colorectal surgery. The efficacy of the combinations of neomyCeftriaxone versus Ceftazidime in Colorectal Surgery 15 Downloaded by: Kings's College London 18.104.22.168 - 10/26/2017 6:18:01 AM cin-erythromycin  and neomycin-metro-nidazole [1, 6, 8] is well established. However, the modes of action of oral antibiotics have been severely criticized because of the risk of encouraging the emergence of resistant organisms in the large bowel, which may then become a reservoir of superinfection. Weaver et al.  do not advise oral antimicrobial prophylaxis in colorectal surgery and believe that it is more effective and safer to use single-dose, long-acting antimicrobial agents that provide high serum and tissue concentrations during the operative period, without disturbing the normal microflora of the colon. Points to be considered are: (1) critical period of contamination: the first hours of potential contamination present the ideal moment for antibiotic prophylaxis ; (2) single versus multiple dose: the risk of emergence of bacterial resistance is minimized with single-dose prophylaxis . Jones et al.  point out that with agents of short half-life, multiple doses are needed. The aim of this study was to compare the efficacy of a single intravenous dose of long-acting ceftriaxone (Rocephin®) with that of ceftazidime, which has a short elimination half-life and is given in multiple doses. Table 1. Bowel preparation, type and duration of operation Downloaded by: Kings's College London 22.214.171.124 - 10/26/2017 6:18:01 AM Ceftriaxone + metronidazole (n = 30) Ceftazidime + metronidazole (n = 30) Mechanical bowel preparations Well prepared 24 Unsufficiently prepared 6 27 3 Operative procedures Rectum resections Abdomino-perineal Others 51 4 5 Left colon resections Low anterior Left hemicolectomy Colostomy/closured 6 1 12 9 18 2 Right colon resections Right hemicolectomy Others 13 4 5 11 3 7 Total colectomy 9 2 10 Duration of operations < 1 hour 1–4 hours > 4 hours 5 23 2 7 23 Patients and Methods A prospective, randomized clinical trial was carried out in 60 patients who underwent elective colorectal surgery. Written informed consent was obtained from all patients. Thirty patients received prophylactic antiinfective treatment with infusions of 2 g ceftriaxone plus 500 mg metronidazole. Ceftazidime (2 g) plus metronidazole (500 mg) were given intravenously to the other 30 patients at 8-hourly intervals for 24 h. Injections were administered 30 min prior to induction of anesthesia. Metronidazole was added to both regimens although ceftriaxone is active against some anaerobes. In all patients, mechanical bowel preparation (colon washout) was performed. The 34 females and 26 males were from 14 to 89 years of age (mean 65 years). The types of operations performed are presented in table 1. The immunologi-cal status and associated diseases of the patients were taken into consideration. 50% of the patients had cancer (19 in the ceftriaxone group and 11 in the ceftazidime group), 13.3% diverticulitis, and 36.7% other pathologies. 16 Palla Garcia/Consiglieri Pedroso Table 2. Site and number of postoperative infections Ceftriaxone Ceftazidimegroup group (n = 30) (n = 30) Local infections Abdominal 1 2 Perineal – 2 Intraperitoneal 1 1 Remote infections Urinary tract 1 2 Respiratory tract 1 2 Total number of infections Staphylococcus aureus E. coli Proteus spp. Klebsiella spp. P. aeruginosa B. fragilis Table 3. Bacteria isolated from infected wounds Downloaded by: Kings's College London 126.96.36.199 - 10/26/2017 6:18:01 AM Ceftriaxone Ceftazidime (n ≈ 30) (n = 30) 1 2 1 1 1 1 1 2 1 Slightly higher risk factors were encountered in the ceftriaxone group: insufficient bowel preparation, more operations with high risk of infection (total colectomy, hemicolectomy) and two operations taking more than 4 h. Bacteria isolated before and after the operation were identified and their sensitivity and minimum inhibitory concentrations (MIC) values determined using standard methods. Patients with established allergy to ß-lactams and pregnant women were excluded from the study. Also excluded from the study was a patient with rectum neoplasia and recent heart failure who had died on the 5th postoperative day with acute renal insufficiency. Written consent was obtained from all patients. Results Postoperative infections are described in table 2. Abdominal wound infections appeared in 3 cases: 1 in the ceftriaxone group (3.3%) and 2 in the ceftazidime group (6.6%), producing a 5% global incidence of infection (3/60 patients). In 1 of these patients an abscess of the abdominal wound developed on the 27th postoperative day and was drained. Bacteriological examination revealed the presence of Escherichia coli together with the anaerobe Bacteroides fragilis. The same organisms had also been isolated preoperatively. Bowel preparation in this patient had been unsatisfactory. Perineal wound infections developed in 2 patients in whom we did not perform primary perineal suture; we used packing procedures for technical reasons. However, they had infections of late development, probably due to the secondary contamination of the open perineal wound. A sepsis developed in 1 patient who had undergone abdominoperi-neal resection for cancer of the rectum. The hemoculture was found positive with Pseu-domonas aeruginosa on the 28th postoperative day. The sepsis was controlled principally with ceftazidime (8 g daily). Intra-abdominal infections: a small colic anastomotic fistula developed on the 22nd postoperative day and healed spontaneously in a patient with serious nutritional problems, which were probably the cause of this complication. Extraabdominal infections (urinary tract plus respiratory tract) were found in a patient with cancer and poor nutritional status. He was treated successfully with 2 g i.v. ceftriaxone for 9 days. Bacteria isolated from the postoperative infections are listed in table 3. The majority Ceftriaxone versus Ceftazidime in Colorectal Surgery 17 Downloaded by: Kings's College London 188.8.131.52 - 10/26/2017 6:18:01 AM were E. coli, Pseudomonas, and B.fragilis. None of the organisms responsible for the postoperative infection were resistant to ceftriaxone or ceftazidime. Adverse events, local or systemic signs, were not observed. Discussion We would like to emphasize that even with very meticulous surgical techniques, bacterial contamination with the subsequent danger of infection continues to be a major factor in postoperative morbidity and mortality. Infection prophylaxis with ceftazidime was certainly an improvement by comparison with prophylaxis with oral antimicrobials. The rate of operative wound infections in our work was 5 %. The infection rate has thus been decreased significantly: in previous studies on the prophylactic use of neo-mycin-erythromycin and neomycin-metro-nidazole, the infection rates had been 18 and 15 %, respectively. Similar results are found in the recent literature, confirming the efficacy of systemic antibioprophylaxis of infections in colorectal surgery. Today, bacterial infections are even more efficiently prevented with ceftriaxone than with ceftazidime, as demonstrated in this study [4, 7, 11]. After a single dose, ceftriaxone concentrations in body fluids and tissues exceeded the minimum inhibitory concentrations for the majority of strains in the colic flora for 24 h or longer, including the critical period of contamination. This was stated by Burdon et al. . They also found that ceftriaxone is clinically more effective in prevention of aerobic infections than any aminoglycoside, broad-spectrum penicillin or cephalosporin previously used in the prophylaxis of colorectal surgery. Single-dose prophylaxis with antimicrobials of short half-life, however, is insufficient in colorectal surgery lasting longer than 2 h. Therefore, repeated doses have to be given while the operation is in progress, in order to maintain effective levels during the whole period of risk. Although the use of broad-spectrum ce-phalosporins as prophylactic agents may be theoretically called into question, the emergence of significantly resistant pathogens due to single-dose prophylaxis has not yet been reported in clinical practice. Ceftazidime was chosen for this study mainly because it is a widely used antibiotic which is well known at Santa Marta Hospital of Lisbon. We agree that it is possible to contend that ceftazidime does not show a suitable profile for the prophylaxis of infection in colorectal surgery, but when associated with metronidazole it covers most of the pathogenic bacteria of the colonic flora (excluding Enterococcus spp.). Very favorably impressed with the good results with ceftriaxone in this study, we are now widely using ceftriaxone/metronidazole for the prophylaxis of infection in colorectal surgery. We are proceeding with another trial, in which we are using 1 g instead of 2 g ceftriaxone plus metronidazole to determine whether this low dose also exhibits the same high efficacy. We conclude that single-dose ceftriaxone plus metronidazole seems to be the ideal combination in the prophylaxis of infection in colorectal surgery because it has a long half-life that provides concentrations exceeding the minimum inhibitory concentration for 14–24h. 18 Palla Garcia/Consiglieri Pedroso Downloaded by: Kings's College London 184.108.40.206 - 10/26/2017 6:18:01 AM Ceftazidime, although more efficient than oral antimicrobials, is clearly inferior to ceftri-axone. Acknowledgement We are thankful to Dr. Luis Laranjeira for the provided statistical data. 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