Comparison of Concentrations of Sulbactam-Ampicillin Administered by Bolus Injections or Bolus plus Continuous Infusion in Tissues of Patients Undergoing Colorectal Surgery

Abstract

The concentrations of sulbactam and ampicillin were determined in sera and different abdominal tissues of 16 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min). This dose was administered again after 2 h by bolus injection by the same route. Patients in group 2 (eight patients) were given the same initial dose of sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of 1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was immediately started and was administered over a 4-h period. Blood samples were collected to determine peak (10 min) and trough (end of surgery) antibiotic levels. Serial blood samples were also collected at predetermined periods (at the time of opening and closing of the abdominal cavity and at the time of surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Similar levels of the drugs in serum were observed for the two regimens of administration, with trough sulbactam levels of 33 ± 16 and 37 ± 22 μg/ml in groups 1 and 2, respectively, and trough ampicillin levels of 72 ± 55 and 79 ± 47 μg/ml in groups 1 and 2, respectively. Similar sulbactam concentrations were observed in abdominal tissues whichever regimen of administration was used; in fatty tissues the sulbactam concentrations ranged from 2.7 to 3.8 μg/g for group 1 and from 1.7 to 4.0 μg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6 ± 7.7 and 6.8 ± 3.2 μg/g in groups 1 and 2, respectively (not significant). Again, no influence of the regimen of administration was observed on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations ranged from 4.1 to 5.4 μg/g for group 1 and from 3.2 to 5.8 μg/g for group 2, and sulbactam concentrations in the colonic wall were 7.0 ± 2.8 and 11.0 ± 4.7 μg/g for groups 1 and 2, respectively (not significant). In most patients, the concentrations of ampicillin-sulbactam were greater than the MIC at which 50% of isolates are inhibited (MIC ₅₀ ) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC ₉₀ for B. fragilis . No influence of the regimen of administration was observed on the ratio of the two components in the tissues investigated and in sera. In conclusion, a second intraoperative bolus injection or a continuous infusion were equally effective in maintaining sulbactam-ampicillin concentrations in abdominal tissues. The first method of administration can be recommended since it is easier to handle.