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 pharmacokinetics.


METHODS
A prospective, open, descriptive study.


METHODS
A 12-bed, adult surgical intensive care unit in a university-affiliated hospital in France.


METHODS
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.


METHODS
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.


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.
Mimoz
O
O
Service d'Anesthésie-Réanimation, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France. o.mimoz@chu-poitiers.fr
Schaeffer
V
V
Incagnoli
P
P
Louchahi
K
K
Edouard
A
A
Petitjean
O
O
Tod
M
M
D018806:APACHE; D000293:Adolescent; D000328:Adult; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D015601:Injury Severity Score; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012039:Regional Blood Flow; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D012774:Shock, Traumatic / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination