B. Sastre

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

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% of the main pathogens tested were considered adequate. The elimination half-life at beta 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 micrograms/g in abdominal-wall fat, 16.4 +/- 1 micrograms/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 micrograms/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 micrograms/g in abdominal-wall fat, 6.1 +/- 4 micrograms/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% of the most frequently encountered pathogenic germs (Staphylococcus aureus, Bacteroides fragilis, 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.

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

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 (greater than or equal to 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 beta-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 greater than or equal to MIC90 for B. fragilis were found in 91% of patients. In the abdominal wall fat and epiploic fat, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 40 to 60% of patients at surgical incision and closure. No anaerobic infection occurred during the study.

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.

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, increased 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.

Pharmacokinetics and Tissue Penetration of a Single Dose of Netilmicin as Antibiotic Prophylaxis in Colorectal Surgery

SummaryThe pharmacokinetics, serum levels and tissue penetration of netilmicin were studied after a single intravenous injection of 6 mg/kg. 13 patients scheduled for elective colorectal surgery and for antibiotic prophylaxis were given a combination of netilmicin and a single dose of ornidazole(1000mg intravenously). Mean maximal (10 minutes) and last determined (24-hour) netilmicin serum levels were 24.4 ± 3.4 and 0.9 ± 0.5 mg/L, respectively. The β-phase elimination half-life was 413 ± 68 minutes, and the apparent volume of distribution and clearance were 0.51 ± 0.12 L/kg and 0.07 ± 0.02 L/min, respectively. In all patients, adequate tissue levels (⩾ MIC90of pathogens) were found in the abdominal wall and epiploic fat at the time of incision and in the colonic wall at the time of anastomosis. At the time of closure, all but 1 patient had adequate tissue levels in the abdominal wall and epiploic fat. Further studies are needed to fully determine the clinical implications of these results but, in view of its pharmacokinetic properties, netilmicin, in combination with ornidazole, can be considered for antibiotic prophylaxis.

Erratum to: Pharmacokinetics and Tissue Penetration of a Single Dose of Netilmicin as Antibiotic Prophylaxis in Colorectal Surgery

SummaryThe pharmacokinetics, serum levels and tissue penetration of netilmicin were studied after a single intravenous injection of 6 mg/kg. 13 patients scheduled for elective colorectal surgery and for antibiotic prophylaxis were given a combination of netilmicin and a single dose of ornidazole(1000mg intravenously). Mean maximal (10 minutes) and last determined (24-hour) netilmicin serum levels were 24.4 ± 3.4 and 0.9 ± 0.5 mg/L, respectively. The β-phase elimination half-life was 413 ± 68 minutes, and the apparent volume of distribution and clearance were 0.51 ± 0.12 L/kg and 0.07 ± 0.02 L/min, respectively. In all patients, adequate tissue levels (⩾ MIC90of pathogens) were found in the abdominal wall and epiploic fat at the time of incision and in the colonic wall at the time of anastomosis. At the time of closure, all but 1 patient had adequate tissue levels in the abdominal wall and epiploic fat. Further studies are needed to fully determine the clinical implications of these results but, in view of its pharmacokinetic properties, netilmicin, in combination with ornidazole, can be considered for antibiotic prophylaxis.