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 (MIC50) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC90 forB. 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.

Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers

“…Data on tissue concentrations after continuous versus bolus application have been sparse to date 28 . However, most infections take place in the extravascular interstitial space, and serum concentrations or serum bactericidal levels are of limited relevance to the clinical outcome.…”

Intravenous Push Administration of Antibiotics: Literature and Considerations

“…27 Although a study in 16 patients undergoing colorectal surgery reported IV push administration of 2 g/1 g ampicillin/ sulbactam over 3 minutes, the concentration of the solution was not reported. 121 Similarly to ampicillin, seizures may occur with rapid administration of ampicillin/sulbactam. 66 Finally, the monobactam aztreonam is indicated for IV push administration after reconstitution of vials.…”

Prophylaxis of Infection for Elective Colorectal Surgery

“…For this reason, clinical studies to prove this administration regimen efficacious continue. Martin et al compared antibiotic concentrations in blood, abdominal wall fat, epiploic fat, and colonic wall tissue samples following administration by consecutive bolus injections versus a bolus injection followed by continuous intravenous infusion [16]. No difference was found in tissue concentrations between the groups, suggesting that a single intravenous bolus of antimicrobials is the preferred method due to increased ease of administration.…”