COMPARISON OF CONCENTRATIONS OF 2 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 e lective colorectal surgery. Patients were randomly allocated to two gr oups. 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 pati ents in group 2 received 400 mg of clavulanic acid with 2,000 mg of am oxicillin. In both groups, the initial dose was administered again aft er 2 h. Blood samples were collected to determine peak and trough anti biotic levels. Serial blood samples were also collected at predetermin ed periods (opening and closure of the abdominal cavity and surgical a nastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously, Antibiotic concentrations were determined hy high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher pea k and trough levels in serum (P < 0.03). Following the injection of 40 0 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concen trations of clavulanic acid and amoxicillin in fatty tissues were 17 t o 52% and 12, to 23% of the levels in sera, respectively. In the colon ic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, c lavulanic acid given at a dose of 200 or 400 mg reached or exceeded th e 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, increasi ng the dose of clavulanic acid to 400 mg resulted in a significantly h igher number of samples with concentrations found to be effective in v itro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improv ed penetration into the abdominal tissues in patients undergoing color ectal surgery.