PHARMACOKINETICS OF AZTREONAM IN CRITICALLY ILL SURGICAL PATIENTS

The pharmacokinetics of aztreonam in critically ill surgical patients with serious gram-negative infections were studied. Blood samples were taken before and at 30 minutes, 2.5 hours, and 5 hours after a dose o f aztreonam 2 g i.v. every six hours. All patients had received at lea st two aztreonam doses before the dosage interval being studied. Aztre onam concentrations were measured by high-performance liquid chromatog raphy. Aztreonam's pharmacokinetics, the severity of illness, and pati ent outcomes were examined. A total of 28 patients with 111 serum aztr eonam concentrations were included in the analysis. The patients were young (mean age, 35 years) and predominantly male. The mean APACHE II score was 19.3, and 22 patients had sepsis. Four patients died. The me an volume of distribution (V) of 0.35 L/kg was nearly twice the previo usly reported steady-state value for healthy volunteers (0.18 L/kg) an d was highly variable. A slightly higher than normal mean V, 0.22 L/kg , was seen in a subset of six patients whose infection occurred earlie r in their intensive care and who had lower APACHE II scores. While wi th some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at o r above the in vitro susceptibility breakpoint of 8 mu g/mL. Despite o bservations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually suff icient to maintain adequate serum drug levels.