Pharmacokinetics and tissue concentrations of ceftazidime in burn patients

Abstract

The pharmacokinetics and tissue concentrations of ceftazidime have been investigated in 8 patients with severe burns (20-80% of body surface area) undergoing skin transplantation 2 to 21 days after injury. Two prophylactic doses of ceftazidime were administered as 1 g i.v. bolus injections with an 8 h interval. Blood, urine, burn blister fluid and tissue were frequently sampled and drug concentrations were analyzed by HPLC. The kinetics of ceftazidime was the same after each dose. In these patients the pharmacokinetics of ceftazidime was greatly altered from that in other patients and there was much interindividual variation. The mean ceftazidime elimination half-life, apparent volume of distribution and total clearance were: 2.7 h, 30.91 (0.38 1.kg-1) and 139 ml.min-1, respectively. A linear correlation was found between creatinine clearance and the renal clearance of the ceftazidime, the mean values being 108 and 95 ml.min-1, respectively. No correlation was found between creatinine clearance and the total clearance of ceftazidime. The mean percentage urine recovery was 69% of the dose. Tissue and burn blister fluid concentrations were above the MIC, and ranged from 40.0 to 3.1 mg.kg-1. A substantial increase in the apparent volume of distribution and non-renal clearance of ceftazidime was observed, probably due to increased capillary permeability and drug loss through the wound surface replacement of prior to surgery and subsequently to lost and blood fluid.

Increased amikacin dosage requirements in burn patients receiving a once-daily regimen

“…Loss of antibiotics through the wound has been shown for other agents [23]. Despite the negative relationship between C max and burn severity demonstrated in our study, which might suggested transwound clearance, we have not found any relationship between Cl AMK and the area and degree of the burn.…”

Aztreonam pharmacokinetics in burn patients

“…The authors concluded that imipenem pharmacokinetics in burn patients were similar to those in normal volunteers. Ceftazidime pharmacokinetics in burn patients have also been reported (24). The authors found that, compared with those of other patients, the apparent volume of distribution, CLNR, and CLT were higher, while tl/23, CLR, and urinary recovery of ceftazidime were lower in burn patients.…”

“…In contrast, there is a dearth of reported information regarding P-lactam antibiotics. Only reports on ceftazidime (24) and imipenem (3) are available.…”

Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

“…These changes often require increased doses to maintain adequate concentrations for successful treatment of severe infections (3,4,12,13,29,34,35). The potential for suboptimal dosing of antibiotics is particularly of concern in this population because of the frequency of infection with difficult, less-susceptible pathogens along with highly variable pharmacokinetics.…”