b-lactam alternatives where toxicity concerns are minimized and larger doses can be safely
utilized.
The data that evaluate other antibiotics in preventive indications in trauma patients is
very limited. Rosemury et al. (4) studied ceftizoxime in 53 celiotomies of trauma patients who
received a conventional dose of preoperative antibiotic. They identified lower antibiotic
concentrations in selected patients in the recovery room, and found that lower postoperative
antibiotic concentrations were predictive of postoperative infections. They identified blood
loss, extensive intraoperative resuscitation, and expandedVdas likely causes for reduced
postoperative antibiotic concentrations and recommended consideration for increased preop-
erative dose of preventive antibiotics. Similarly, Dalley et al. (5) studiedb-lactam antibiotics
used for prophylaxis in burn surgery and found inadequate plasma concentrations for targeted
organisms. They recommended re-dosing or continuous infusion as a requirement for effective
use of preventive antibiotics in this population.
Aminoglycosides
The aminoglycosides more than any antibiotic group have been studied most extensively in
the setting of critical illness. Nephro- and ototoxicity have been the driving issues that have
stimulated pharmacokinetic studies of the aminoglycosides. However, the data indicate that
perhaps more patients have been underdosed than have received toxic levels of these
antibiotics. Given that gentamicin and the other aminoglycosides have been demonstrated to
have highly variable pharmacokinetics even with patients that appear to have normal kidney
function (6), it is not surprising that physiologic changes of trauma and clinical fever will
further compound an already difficult situation.
Niemiec et al. (7) studied 100 trauma and other surgical patients in the surgical intensive
care unit. All study patients received at least one aminoglycoside with the majority receiving
gentamicin or tobramycin. TheVdincreased approximately 50% greater than normal for this
population with one patient demonstrating a threefold increase. TheT1/2was highly variable
with a range from 1.6 to 63 hours;T1/2 increased with age. Using individual patient
pharmacokinetic parameters, adjustments in gentamicin doses ranged from 1.4 to 15.5 mg/kg/
day for these patients. In similar studies by Reid et al. (8), gentamicin and tobramycin were
both found to require dramatic increases in the dosing of the drug in intensive care unit
patients largely due to the increasedVd that was observed. In this latter study, drug
elimination rates were strongly influenced by the patient’s serum creatinine as a marker of
clinical renal function. Despite larger doses that were required, doses of the aminoglycosides
were given less frequently with patients having a creatinine above 1 mg/dL.
Summer et al. (9) studied 22 sepsis/septic shock patients following the administration of
intravenous tobramycin at 2 mg/kg. They identified 59% of patients that had blood concentration
of the antibiotic that was significantly below expected concentrations. The expandedVdwas
considered to be responsible for the low blood concentrations.
Dasta and Armstrong (10) studied aminoglycoside pharmacokinetics in 181 critically ill
patients in a surgical intensive care unit. TheVdwas identified at 0.36 L/kg which was 60% to
70% above expected normal. TheT1/2was highly variable with a range of 1.1 to 69.3 hours.
Additional studies have validated that the observations of increasedVdand highly variable
T1/2are applicable to all of the aminoglycosides in trauma (11) and intensive care unit
patients (12).
Understanding these changes of aminoglycosides under circumstances of trauma, fever,
and critical illness should lead to pharmacokinetic dosing and changes in the management of
these patients. Zaske et al. (13) reported improved survival in burn patients undergoing dosing
changes to address the pharmacokinetic changes. Once-daily dosing of aminoglycosides has
become very common at present, but again the pharmacokinetic observations have
demonstrated that conventional doses will be inadequate, especially for the younger trauma
patient with normal renal function.
Vancomycin
Like the aminoglycosides, the pharmacokinetics of vancomycin is highly variable among
patients with normal renal function (14). Reid et al. (7) studied the pharmacokinetics of
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