[The reliability of using impenem, meropenem, cefoperazone-sulbactam and piperacillin-tazobactam to treat nosocomial Gram-negative bacterial infections with Monte Carlo simulation].

Objective: To evaluate the reliability of using imipenem, meropenem, cefoperazone-sulbactam, piperacillin-tazobactam in the treatment of hospital-acquired Gram-negative bacterial infections with Monte Carlo simulation(MCS). Methods: The MIC of the four agents collected from hospital-acquired infections were detected in accordance with broth dilution method of Clinical and Laboratory Standard Institute (CLSI). MCS were conducted with MICs and the pharmacokinetics parameters of the four agents based on conventional dose regimens.The cumulative fraction of response (CFR) of time over MIC target attainment in different dosing regimen were generated. Results: A total of 2 541 strains, including 2 093 strains of Enterobacteriaceae and 448 strains of glucose non - fermentative bacilli were collected.The MIC(90) of imipenem and meropenem against Enterobacteriaceae were less than 1 mg/L in general, whereas MIC(90) of two agents with β-lactamase inhibitors was around 64 mg/L.As to glucose non - fermenting bacteria, MICs of all the four agents were very high, especially to Acinetobacter baumannii, which indicated MIC(50) more than 32 mg/L.MCS revealed that carbapenems had significantly higher CFR than those with β-lactamase inhibitors.Imipenem and meropenem (1 g, q8 h) obtained CFRs of 74.69% and 81.42%, respectively.The CFR of cefoperazone-sulbactam (2 g, q8 h) and piperacillin-tazobactam (4 g, q6 h) (both excluding β-lactamase inhibitors) were just 49.59% and 27.66% respectively, which increased after excluding A . baumannii in piperacillin-tazobactam. Conclusions: The conventional dose regimens of imipenem and meropenem are reliable for the empiric therapy of Gram-negative hospital-acquired bacterial infections.Piperacillin-tazobactam is suggested to use with higher doses or prolonged infusion time to satisfy the time of drug concentration exceeded the MIC(T>MIC)requirement.More clinical studies of cefoperazone-sulbactam should be conducted to optimize its regimen and guarantee its efficacy.