PHARMACOKINETICS OF AZTREONAM AND IMIPENEM IN CRITICALLY ILL PATIENTSWITH PNEUMONIA

Study Objective. To evaluate the pharmacokinetic profiles of aztreonam and imipenem in critically ill trauma patients with pneumonia. Method s. Trauma patients in intensive care units who were intubated within 3 days of hospital admission were eligible for the study. Patients with the clinical diagnosis of pneumonia were consecutively randomized to receive either aztreonam plus vancomycin or imipenem-cilastatin. Seria l blood samples were taken and sputum was collected to determine aztre onam and imipenem concentrations after 2-3 daps and 7-8 days of therap y. Pharmacokinetics of both agents were estimated and compared with es timates from healthy volunteers. Results. Twenty patients were enrolle d in the study, 10 patients received imipenem-cilastatin, and 10 recei ved aztreonam plus vancomycin. Steady-state volume of distribution (V- ss) for aztreonam at 2-3 days and 7-8 days was significantly greater i n patients than in historical controls, whereas the V-ss for imipenem was greater at 2-3 days. The beta-half-life for aztreonam at both samp ling periods was significantly greater in patients than in controls. N o significant changes in pharmacokinetics occurred over time for eithe r antibiotic. Sputum concentrations of aztreonam and imipenem were hig hly variable when sampled 2 hours after the infusion. Conclusion. Larg er volumes of distribution were observed for both aztreonam and imipen em in trauma patients than in volunteers, suggesting that standard ini tial dosages of the antibiotics may result in lower concentrations in these critically ill patients. Both antibiotics penetrated into the sp utum of most. patients; however, the degree of penetration was highly variable in relation to serum concentrations.