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目的:监测几种临床常用抗菌药物对肺炎克雷伯杆菌最低抑菌浓度(MIC)变化情况,在临床工作中帮助选择合理的初始化抗菌治疗方案。方法:本研究选择哌拉西林他唑巴坦、头孢哌酮舒巴坦、拉氧头孢钠、左氧氟沙星及头孢他啶5种常用的抗革兰氏阴性杆菌感染的治疗药物作为初始经验性治疗方案,使用随机法将5种抗菌方案分配到5个观察组,5个观察组于2011.07-2012.07间各自采集HAP患者痰标本,筛选出其中ESBLs(-)肺炎克雷伯杆菌资料,并于2012.08-2013.08间分别使用1种拟定的抗菌治疗方案进行HAP的初始化治疗。使用Crystal Ball软件进行蒙特卡罗模拟计算上述5种药物常用方案的两个阶段的累计反应分数(CFR),比较其效果。结果:(1)在按规定方案治疗1年后,头孢哌酮钠舒巴坦、哌拉西林他唑巴坦、拉氧头孢钠、左氧氟沙星组有效率改变均无统计学意义,头孢他啶组固定初始化治疗1年后有效率下降,有统计学意义(P=0.037);(2)对各科室初始化方案再次进行了蒙特卡罗模拟,对比后发现头孢他啶方案CFR较前下降明显,其余方案CFR差异小。结论:蒙特卡罗模拟法可计算出用药方案达到药效学指标的概率,以CFR为标准可以更为直观的选择经验性治疗方案,并有效的监测细菌耐药性的变化。
Objective: To monitor the change of minimum inhibitory concentration (MIC) of several commonly used antibacterials against Klebsiella pneumoniae in clinical practice and to help select a reasonable initial antibacterial treatment regimen. Methods: In this study, five commonly used anti-Gram-negative bacilli drugs, piperacillin-tazobactam, cefoperazone-sulbactam, cefoxitin sodium, levofloxacin and ceftazidime, were selected as the initial empirical treatment. Five kinds of antibacterial regimens were assigned to five observation groups randomly. Five observation groups were collected sputum specimens of patients with HAP from 2011.07 to 2012.07. ESBLs - (-) Klebsiella pneumoniae was screened out in the data of 2012.08-2013.08 An initial antimicrobial regimen was used to initiate HAP treatment. Monte Carlo simulations using Crystal Ball software were used to calculate the cumulative response fraction (CFR) over the two phases of the five commonly used regimens described above, and their effects were compared. Results: (1) There was no significant change in the effective rate of cefoperazone sodium and sulbactam, piperacillin-tazobactam, dexamethasone sodium and levofloxacin after 1 year of treatment according to the prescribed protocol. The ceftazidime group was initially treated for 1 year (P = 0.037). (2) Monte Carlo simulation was performed again on the initial programs in different departments. The comparison showed that the CFR of ceftazidime was significantly lower than before, and the differences of other programs were small. CONCLUSIONS: The Monte Carlo simulation method can calculate the probability that the drug regimen will achieve the pharmacodynamic index. CFR can be used as the standard to select the empirical treatment plan more intuitively and effectively monitor the change of bacterial drug resistance.