OBJECTIVE: To determine the effects of severe trauma with hemorrhagic shock on amoxicillin and clavulanate concentrations in plasma and their pharmacokinetics. DESIGN: A prospective, open, descriptive study. SETTING: A 12-bed, adult surgical intensive care unit in a university-affiliated hospital in France. SUBJECTS: Subjects were 12 patients (10 men, 2 women) with severe trauma: median (range) Injury Severity Score, 38 (17-48); Acute Physiology and Chronic Health Evaluation II, 16 (7-38); Simplified Acute Physiology Score II, 41 (23-77). Also enrolled were 12 healthy volunteers who were matched on age (+/-5 yrs), gender, and body-surface area (+/-20 cm2). 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 volume expansion >2000 mL between trauma and surgery. INTERVENTION: Prophylactic perioperative administration of 2 g of amoxicillin and 0.2 g of clavulanate in combination during the first 12 hrs posttrauma 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 volunteers, trauma patients had higher plasma amoxicillin and clavulanate concentrations, attributed to a reduction of the volume of distribution (p =.001 and p =.06, respectively) and, to a lesser extent, of the total body clearance (p =.09 and p =.20, respectively). Consequently, amoxicillin and clavulanate elimination half-lives were similar for the two groups of subjects. The interindividual variabilities for all the amoxicillin pharmacokinetic parameters were higher in patients. CONCLUSIONS: In trauma patients with hemorrhagic shock requiring surgery, the administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adequate, according to the antibiotic concentrations observed in plasma for both drugs. However, further studies exploring antibiotic concentrations in tissues are warranted.
OBJECTIVE: To determine the effects of severe trauma with hemorrhagic shock on amoxicillin and clavulanate concentrations in plasma and their pharmacokinetics. DESIGN: A prospective, open, descriptive study. SETTING: A 12-bed, adult surgical intensive care unit in a university-affiliated hospital in France. SUBJECTS: Subjects were 12 patients (10 men, 2 women) with severe trauma: median (range) Injury Severity Score, 38 (17-48); Acute Physiology and Chronic Health Evaluation II, 16 (7-38); Simplified Acute Physiology Score II, 41 (23-77). Also enrolled were 12 healthy volunteers who were matched on age (+/-5 yrs), gender, and body-surface area (+/-20 cm2). All the traumapatients suffered hemorrhagic shock defined as the association of at least one episode of systolic blood pressure <90 mm Hg and an intravascular volume expansion >2000 mL between trauma and surgery. INTERVENTION: Prophylactic perioperative administration of 2 g of amoxicillin and 0.2 g of clavulanate in combination during the first 12 hrs posttrauma 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 volunteers, traumapatients had higher plasma amoxicillin and clavulanate concentrations, attributed to a reduction of the volume of distribution (p =.001 and p =.06, respectively) and, to a lesser extent, of the total body clearance (p =.09 and p =.20, respectively). Consequently, amoxicillin and clavulanate elimination half-lives were similar for the two groups of subjects. The interindividual variabilities for all the amoxicillin pharmacokinetic parameters were higher in patients. CONCLUSIONS: In traumapatients with hemorrhagic shock requiring surgery, the administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adequate, according to the antibiotic concentrations observed in plasma for both drugs. However, further studies exploring antibiotic concentrations in tissues are warranted.
Authors: Dagan O Lonsdale; Emma H Baker; Karin Kipper; Charlotte Barker; Barbara Philips; Andrew Rhodes; Mike Sharland; Joseph F Standing Journal: Br J Clin Pharmacol Date: 2018-11-26 Impact factor: 4.335