美罗培南fT>MIC计算公式的比较及对常见细菌感染的给药方案选择

Comparison of fT>MIC Formulas for Meropenem and Its Dosage Regimen Selection for Common Bacterial Infections

目的:讨论用于计算美罗培南PK/PD效应的fT>MIC静推公式和静滴公式能否相互替代使用,并基于%fT>MIC探讨如何选择美罗培南对常见细菌感染的给药方案(包括给药方式)。方法:以美罗培南0.5gq8h、1gq8h和2gq8h为考察方案,以0.5h输注、3h输注及静注给药为考察的给药方式,以MIC敏感性折点为0.002~8mg·L-1的细菌为目标菌群,计算上述方案在各给药方式下对各目标菌群的fT>MIC和%fT>MIC值。同一方案对同一MIC敏感性折点的fT>MIC值可根据给药方式的不同按静滴公式和静注公式计算,结果组成一个对子。所有方案对所有MIC敏感性折点的fT>MIC值将组成多个对子。对所有对子进行配对t检验,考察fT>MIC静注公式和静滴公式能否相互替代使用。最后根据%fT>MIC值探讨如何选择美罗培南对常见细菌感染的给药方案(包括给药方式)。结果与结论:计算美罗培南fT>MIC的静注公式和静滴公式不能相互替代使用。fT>MIC的计算应与其给药方式相符,即静滴给药时应依据其静滴公式,静注给药时应依据其静注公式。依据%fT>MIC值来选择美罗培南的给药方案,即使对同一目标菌群,美罗培南要想获得良好的抗菌效果,除给药剂量和给药间隔合理外,还应选择正确的给药方式。

Objective: To discuss whether the formulas of fT>MIC used to calculate the PK/PD effect of meropenem respectively for iv-bolus and iv-infusion are mutual substitution,and how to select its dosage regimens including the administration mode for infections caused by common bacteria according to %fT>MIC. Methods: The dosage regimens of 0.5 g/q 8 h,1 g/q 8 h and 2 g/q 8 h for meropenem were applied as the studied ones,0.5 h-infusion,3 h-infusion and iv-bolus were used as the studied mode of administration,and the bacteria with sensitivity breakpoints of 0.002-8 mg·L-1 were applied as the targeted bacteria,and the values of fT>MIC and % fT>MIC of each dosage regimen of meropenem against each targeted bacterium were calculated under each mode of administration. Each value of fT>MIC could be calculated by both the iv-bolus and iv-infusion model of fT>MIC according to the mode of administration,as a result,formulated a pair of fT>MIC of each regimen for each MIC. By analogy,the values of fT>MIC of all the regimens against all the MIC sensitivity breakpoints formed multiple pairs. Paired sample t-test was used to checkout the differences of all pairs of fT>MIC calculated by the two models so as to discuss whether the two models were mutual subsitution. Finally,how to select the dosage regimen including the mode of administration for meropenem in the treatment of infections caused by different bacteria according to the values of %fT>MIC was discussed. Results and Conclusion: The formulas of fT>MIC based on iv-bolus and iv-infusion are not mutual subsitution. The calculation of fT>MIC should be consistent with the mode of administration,namely,the values of fT>MIC should be calculated by the formula of fT>MIC based on iv-bolus when the antibiotic agent is administrated by iv-bolus,and by the formula of fT>MIC based on iv-infusion when the antibiotic agent is administrated by iv-infusion. According to the values of %fT>MIC,in order to obtain good antimicrobial effect,meropenem should not only be administrated with reasonable dosage and frequency,but also with correct mode of administration,even for the same targeted bacteria.