Pharmacokinetics of aztreonam in critically ill surgical patients
E E Cornwell1, H Belzberg, T V Berne
1School of Medicine, University of Southern California (USC), USA.
Abstract:
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 of aztreonam 2 g i.v. every six hours. All patients had received at least two aztreonam doses before the dosage interval being studied. Aztreonam concentrations were measured by high-performance liquid chromatography. Aztreonam's pharmacokinetics, the severity of illness, and patient outcomes were examined. A total of 28 patients with 111 serum aztreonam 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 mean volume of distribution (V) of 0.35 L/ kg was nearly twice the previously reported steady-state value for healthy volunteers (0.18 L/kg) and 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 earlier in their intensive care and who had lower APACHE II scores. While with some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at or above the in vitro susceptibility breakpoint of 8 micrograms/mL. Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.
Insights
Critically ill surgical patients receiving aztreonam showed a larger volume of distribution (V) than healthy individuals. However, standard aztreonam dosing effectively maintained therapeutic drug levels, indicating its suitability for severe gram-negative infections.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Critically ill surgical patients often present with altered pharmacokinetics.
- Serious gram-negative infections necessitate effective antibiotic therapy.
- Understanding aztreonam's behavior in this population is crucial for optimizing treatment.
Purpose of the Study:
- To investigate the pharmacokinetics of aztreonam in critically ill surgical patients.
- To correlate aztreonam concentrations with illness severity and patient outcomes.
- To assess the adequacy of standard aztreonam dosing in this patient group.
Main Methods:
- Studied 28 critically ill surgical patients with gram-negative infections.
- Measured serum aztreonam concentrations using high-performance liquid chromatography.
- Analyzed pharmacokinetic parameters, including volume of distribution (V), alongside clinical data (APACHE II scores, outcomes).
Main Results:
- Mean volume of distribution (V) was 0.35 L/kg, nearly double that of healthy volunteers (0.18 L/kg) and highly variable.
- Despite increased V, 89% of serum aztreonam concentrations met or exceeded the susceptibility breakpoint (8 µg/mL).
- A subset of patients with less severe illness had a V closer to normal values.
Conclusions:
- Aztreonam exhibits increased and variable volume of distribution in critically ill surgical patients.
- Standard aztreonam dosing (2 g IV q6h) is generally sufficient to achieve therapeutic levels in this population.
- Aztreonam remains a viable option for treating serious gram-negative infections in critically ill surgical patients.
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