Abstract: AIM: To evaluate pharmacodynamic profiling of dosage regimens of four β-lactam antibiotics against severe infection. METHODS: Minimum inhibitory concentrations for 120 Gram-negative bacteria from patients managed in intensive care unit were determined. A 10 000-subject Monte Carlo simulation was performed to calculate pharmacodynamic target attainment for traditional infusion and prolonged dosing regimens of 1,2,3,4 h and 5 h infusion of ceftazidime,piperacillin-tazobactam,imipenem and meropenem. RESULTS: No regimen of traditional infusion achieved cumulative fraction of response (CFR) of greater than 90%.Increasing doses,increasing frequencies and prolonging infusion time regimens achieved higher CFR.The results of prolonged infusion of 1,2,3,4 h and 5 h were as follows. When the infusion time of piperacillin-tazobactam 4.5 g q8 h was gradually prolonged,the highest CFR was achieved by a 5 h prolonged infusion. However, the highest CFR was achieved by 3 h prolonged infusion for dosage regimens of ceftazidime 2 g q6 h,imipenem 0.5 g q6 h,1 g q6 h and meropenem 0.5 g q6 h, 84.38%,78.50%,87.03%,81.53%,respectively.The highest CFR was achieved by 4 h prolonged infusion for dosage regimens of ceftazidime 2 g q8 h,piperacillin-tazobactam 4.5 g q6 h,imipenem 1 g q8 h and meropenem 1 g q8 h、2 g q8 h, 83.12%,89.94%,83.87%,82.29%,86.98%,respectively. CONCLUSION: As a result of high resistance rate in intensive care unit, no regimen attains optimal bactericidal exposure against severe infection. Prolonged infusion regimens improve pharmacodynamic target attainment.3 h or 4 h is probably optimal infusion time.

Key words: monte carlo simulation, pharmacodynamics, severe infection, prolonged infusion