Effects of prophylactic antibiotics on wound infection after elective colon and rectal surgery: 1960 to 1980

Mallet

Sastre

et al. 1995

The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increasing the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.

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confidence: 99%

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confidence: 99%

Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery

Mallet

Sastre

et al. 1995

“…Antimicrobial agents for prophylaxis should be selected on the basis of their spectrum of activity against pathogens most likely to contaminate the surgical wound (11). Since Bacteroides fragilis and other anaerobic bacteria are among the main pathogens encountered in infections after colorectal surgery, antibiotics with a spectrum of activity extended to these organisms are usually advocated (1). Antibiotic regimens which do not eliminate anaerobic fecal pathogens fail to control postoperative septic complications of colorectal operations (5,13).…”

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confidence: 99%

Pharmacokinetics and tissue penetration of a single dose of ornidazole (1,000 milligrams intravenously) for antibiotic prophylaxis in colorectal surgery

Bruguerolle

Mallet

et al. 1990

Levels in serum and tissue penetration of ornidazole were studied after a single intravenous injection of 1,000 mg given to 14 patients for prophylaxis of surgical infection. They were scheduled for elective colorectal surgery. Adequate levels in blood (2MIC for 90% of Bacteroides fragilis strains tested) were found in all patients throughout the procedure and up to hour 24. Mean-maximal (15 min) and last-determined (24 h) ornidazole levels in serum were 24 5.2 and 6.3 1.4 mg/liter, respectively. 13-Phase elimination half-life was 14.1 + 2.7 h, and clearance and apparent volume of distribution were 47 + 12 ml/min and 0.9 + 0.13 liters/kg, respectively. In all patients, adequate levels in tissue were found in the abdominal wall and the epiploic fat at time of incision and in the colonic wall at time of anastomosis. At time of closure, all but one patient had adequate levels in tissue in the abdominal wall and the epiploic fat. No anaerobic nor aerobic infection occurred in the study patients.The benefit of short-term antimicrobial courses for prevention of postoperative infection has been demonstrated for selected surgical procedures, among them colorectal surgery (4,11,23). Antimicrobial agents for prophylaxis should be selected on the basis of their spectrum of activity against pathogens most likely to contaminate the surgical wound (11). Since Bacteroides fragilis and other anaerobic bacteria are among the main pathogens encountered in infections after colorectal surgery, antibiotics with a spectrum of activity extended to these organisms are usually advocated (1). Antibiotic regimens which do not eliminate anaerobic fecal pathogens fail to control postoperative septic complications of colorectal operations (5, 13).Nitroimidazole derivatives such as metronidazole are commonly used in this situation (3,8,12,22 MATERIALS AND METHODSThis study received the approval of the ethical committee of our institution, and all patients gave their informed consent. Fourteen patients were scheduled for elective rectal or colonic surgery. They were 10 men and 4 women with a mean age of 66 5 years and a mean weight of 67 + 8 kg. None had a history of allergic reaction to ornidazole. All patients had normal renal and hepatic function. They had a 2-day mechanical bowel preparation consisting of low-residue diet, purgation, and bowel washouts in the evening. Patients did not present any clinical or laboratory signs of infection and were not receiving any antibiotic therapy before surgery. Before induction of anesthesia, patients were given a single dose of 1,000 mg of ornidazole intravenously (i.v.) administered over 30 min via an arm catheter, at a constant flow rate with an automatic pump. Blood samples were collected from a central venous line (right internal jugular vein) before ornidazole injection and 15 min (maximum concentration), 45 min, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24

“…The basic principles of antibiotic prophylaxis have been established by previous studies, and the main points are that (i) the antimicrobial agent must be present in the involved tissues before surgery allows bacterial contamination and (ii) the drug must attain and maintain antibiotic concentrations in blood and tissue high enough to inhibit the growth of contaminating pathogens (1,4,8,13). …”

Section: Discussionmentioning

confidence: 99%

“…The principal pathogens under consideration in colorectal surgery are Bacteroides fragilis and other anaerobic germs, Staphylococcus aureus, and members of the family Enterobactenaceae, including Eschenchia coli (1,2,8,13). In such surgery, contamination may occur in the parietal tissue, with the risk of abscess or cellulitis, and in the abdomen, with the risk of peritonitis and intra-abdominal abscess.…”

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confidence: 99%

Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery

Portet

Lambert

et al. 1992

The pharmacokinetics and tissue penetration of cefotetan were studied after a single injection of 2 g given intravenously for antimicrobial prophylaxis to 16 consecutive patients undergoing colorectal surgery. Concentrations in tissue greater than or equal to the MIC for 90%1 of the main pathogens tested were considered adequate. The elimination half-life at , phase was 4.6 + 1.4 h, the total body clearance was 0.75 + 0.19 ml/kg/min, and the volume of distribution was 260 + 71 ml/kg. At the time of incision (33 + 16 min after the injection), cefotetan concentrations were 14.2 7 ,g/g in abdominal-wall fat, 16.4 1 ,ug/g in epiploic fat, and 163 + 62 mg/liter in serum. At the time of surgical anastomosis (151 54 min), cefotetan concentrations were 33.3 6 ,ug/g in the colonic wall and 73 34 mg/liter in serum. Upon closure of the abdomen (216 + 76 min), cefotetan concentrations were 6.3 + 3 ,ug/g in abdominal-wall fat, 6.1 + 4 ,Ig/g in epiploic fat, and 64 + 38 mg/liter in serum. Cefotetan tissue penetration was 10% into abdominal and epiploic fat and 46% into the colonic wall. Levels in tissue were compared with the MIC for 90%o of the most frequently encountered pathogenic germs (Staphylococcus aureus, Bacteroidesjfragilis, and Escherichia coli). Adequate concentrations in tissue were obtained up to anastomosis but not upon closure. The authors therefore recommend the injection of an additional dose of 1 g before closure in order to ensure optimal efficacy throughout the surgical procedure.