Aztreonam pharmacokinetics in burn patients

Abstract

The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% + 21% [mean + standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 ± 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients.

Pharmacokinetics and Pharmacodynamics of Antibacterial and Antifungal Agents in Adult Patients With Thermal Injury

“…This study demonstrated an increase in CL T 9.2 days after injury which was best explained by an increase in patients' CL CR and an increase in V d (27.1 L vs 16.8 L in healthy volunteers), as previously observed with other β-lactam antibiotics. 14,18,19,22,27 The mean albumin concentration among these patients was 2.7 g/dl which may provide an explanation for the observed increase in the volume of distribution.…”

“…22 Similar to cefepime, CL T and CL R were strongly correlated with CL CR . Additionally, there was a documented increase in V d of aztreonam (0.27 L/kg) 7 days out from initial injury compared with healthy volunteers (0.18 L/kg).…”

Clinical Pharmacokinetics of Aztreonam

“…Mean plasma protein binding in these patients was much lower than that in healthy volunteers (30 vs 56%). Other investigators found a higher Vd (0.26 ± 0.08 L/kg) in 22 similar patients (Mattie & Matze-van der Lans 1986) and in 7 patients with severe burn injuries who received aztreonam for Gram-negative infection (Vd 0.27 ± 0.04 Llkg after the first dose) [Friedrich et al 1991]. Serum albumin levels were low in these patients, and there was a significant correlation between V ss and the albumin level, in the 5 patients for whom steady-state pharmacokinetic parameters were determined.…”

Continuous Infusion of Beta-lactam Antibiotics

“…Aztreonam administered to healthy adults has a Vd of 0.16 ± 0.02 L/kg, whereas the Vd in burn patients has been demonstrated to be 0.31 ± 0.08 L/kg (Friedrich et al 1991). For imipenem, higher values for Vd were also reported in burn patients compared to healthy adults (Dailly et al 2003).…”