Prophylactic Peroperative Intravenous Metronidazole in Elective Colorectal Surgery

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

“…Prophylaxis directed only against anaerobic pathogens has been recommended in colorectal surgery (8,10,14,18). In the present study, no case of postoperative infection was observed.…”

Section: Discussionsupporting

confidence: 47%

mentioning

confidence: 99%

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

Martin

Bruguerolle

Mallet

et al. 1990

“…Prophylaxis directed only against anaerobic pathogens has been recommended in colorectal surgery (7,8,12,16). In the present study, two cases of infection related to aerobic pathogens were observed.…”

Section: Resultssupporting

confidence: 51%

“…Since Bacteroides fragilis and other anaerobic bacteria are among the main pathogens encountered in infections after colorectal surgery, antimicrobial agents with a spectrum of activity against these organisms are most often advocated (1). Nitroimidazole derivatives, such as metronidazole or ornidazole, are commonly used (1,4,7,10,11). During colorectal surgery, bacterial contamination occurs primarily in two sites: (i) soft tissues with the risk of abcess or cellulitis and (ii) the abdominal cavity with the risk of peritonitis or intraabdominal abscess.…”

mentioning

confidence: 99%

Pharmacokinetics and tissue penetration of a single 1,000-milligram, intravenous dose of metronidazole for antibiotic prophylaxis of colorectal surgery

Martin

Sastre

Mallet

et al. 1991

The levels of metronidazole in serum and tissue penetration of metronidazole were studied after prophylactic administration in 11 patients undergoing elective colorectal surgery. A single dose of 1,000 mg given intravenously was administered before surgery. Adequate drug levels in serum (.MIC for 90% of strains tested [MIC90] for Bacteroides fragilis) were found in all patients throughout the procedure. Mean peak (15-min) and last-determined (24-h) metronidazole levels in serum were 28.8 ± 8 and 4.2 ± 1.7 mg/liter, respectively. The n-phase elimination half-life was 9.5 ± 2.3 h, and the clearance and apparent volume of distribution were 57 ± 13 ml/min and 0.7 ± 0.1 liter/kg, respectively. In the colonic wall at surgical anastomosis, tissue metronidazole levels .MIC90 for B. fragiis were found in 91% of patients. In the abdominal wall fat and epiploic fat, tissue metronidazole levels .MIC90 for B. fragilis were found in 40 to 60% of patients at surgical incision and closure. No anaerobic infection occurred during the study.

“…Many other broad-spectrum antibiotics have been evaluated as single prophylactic agents in colorectal surgery, for example, piperacillin and metronidazole, among others (7,11). In a limited trial, piperacillin was efficacious.…”

Section: Resultsmentioning

confidence: 99%

Suppression of colonic microflora by cefoperazone and evaluation of the drug as potential prophylaxis in bowel surgery

Silva

Cornick

Gorbach

1989

We evaluated the activity of cefoperazone (CPZ) on the intestinal flora in terms of its use as a single prophylactic drug in colon surgery. Twenty-four healthy male volunteers between the ages of 20 and 40 were assigned to receive either CPZ, oral neomycin-erythromycin, or no antibiotics. A mechanical bowel preparation, Golytely, was also given to each of the subjects. With intravenous CPZ, antibiotic levels in the stool ranged from <2 to 649 ,ug/ml and the total fecal bacterial counts dropped 3 to 4 log1o CFU/g. Higher levels of CPZ were detected in the stools when an oral dose was added, 1,446 to 5,445 ,ug/ml, and the bacterial counts were reduced maximally 4 to 6 loglo CFU/g. The combination of the oral and intravenous doses produced suppression of the microflora and high levels in blood, all with a single antibiotic.The most widely accepted form of antimicrobial prophylaxis for elective colorectal surgery in the United States is the combination of oral neomycin-erythromycin in a threedose schedule, administered at 1, 2, and 11 p.m. the day before surgery (16). It is becoming commonplace to combine this oral regimen with a parenteral cephalosporin antibiotic in order to provide levels of antibiotic in blood and enhance systemic protection. Some studies have suggested that the third drug, usually a cephalosporin with activity against Bacteroides fragilis, provides protection superior to that provided by the oral drugs alone (6, 18). This point remains controversial, however, because postoperative infection rates in the groups receiving the oral preparation alone are usually higher (-15%) than those reported in the earlier large-scale Veterans Administration cooperative studies that established the efficacy of the neomycin-erythromycin preparation (6 to 9%) (5).The rationale for the oral antibiotic bowel preparation is suppression of the intestinal microflora so that any leakage of luminal contents would contain a low inoculum of microorganisms (19). The parenteral antibiotic is thought to add another barrier to tissue invasion by organisms in the microflora by creating a level of antibiotic in blood.In addition to the antimicrobial regimen, mechanical cleansing is of fundamental importance in reducing the bacterial burden. However, in patients who are operated on urgently or who have bowel obstruction, it may not be possible to effect mechanical cleansing or to administer an oral regimen, and the main burden for prophylaxis in these high-risk patients falls upon the parenterally administered drug(s). Despite the preliminary evidence that there is a benefit from concomitant oral and parenteral antibiotics in prophylaxis for bowel surgery, there are clear concerns about such an approach from the aspects of drug toxicity, antibiotic resistance, and cost (19). Thus, there would be considerable interest in a regimen which meets the same objectives with a single drug. MATERIALS AND METHODSSubjects. Twenty-four healthy males, ages 20 to 40 years, were studied. They underwent a complete physical examination and routin...