Co-amoxiclav pharmacokinetics during posttraumatic hemorrhagic shock

Objective: To determine the effects of severe trauma with hemorrhagic shock on amoxicillin and clavulanate concentrations in plasma and their pharmaco kinetics. Design: A prospective, open, descriptive study. Setting: A 12-bed, adult surgical intensive care unit in a university-affil iate hospital in France. Subjects: Subjects were 12 patients (10 men, 2 women) with severe trauma: m edian (range) Injury Severity Score, 38 (17-48); Acute Physiology and Chron ic Health Evaluation II, 16 (7-38); Simplified Acute Physiology Score 11, 4 1 (23-77). Also enrolled were 12 healthy volunteers who were matched on age (+/- 5 yrs), gender, and body-surface area (+/- 20 cm(2)). All the trauma patients suffered hemorrhagic shock defined as the association of at least one episode of systolic blood pressure < 90 mm Hg and an intravascular volu me expansion > 2000 mL between trauma and surgery. Intervention: Prophylactic perioperative administration of 2 g of amoxicill in and 0.2 g of clavulanate in combination during the first 12 hrs posttrau ma in patients, and at the start of the pharmacokinetic study in volunteers . Measurements and Main Results: Serial plasma samples (n = 13) were obtained after the first antibiotic administration to measure antibiotic levels by using high-performance liquid chromatography assays. Compared with voluntee rs, trauma patients had higher plasma amoxicillin and clavulanate concentra tions, attributed to a reduction of the volume of distribution (p = .001 an d p = .06, respectively) and, to a lesser extent, of the total body clearan ce (p = .09 and p = .20, respectively). Consequently, amoxicillin and clavu lanate elimination half-lives were similar for the two groups of subjects. The interindividual variabilities far all the amoxicillin pharmacokinetic p arameters were higher in patients. Conclusions: In trauma patients with hemorrhagic shock requiring surgery, t he administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adeq uate, according to the antibiotic concentrations observed in plasma for bot h drugs. However, further studies exploring antibiotic concentrations in ti ssues are warranted.