Simulating moxalactam dosage for extended-spectrum β-lactamase-producing Enterobacteriaceae using blood antimicrobial surveillance network data
Simulating moxalactam dosage for extended-spectrum β-lactamase-producing Enterobacteriaceae using blood antimicrobial surveillance network data
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DOI：
10.2147/idr.s193712
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Xiao, Yonghong
中科院分区：
文献类型：
--
作者：
Huang, Chen;Shi, Qingyi;Xiao, Yonghong
目的：用蒙特卡罗模拟(MCS)法评价头孢吡肟(FEP)、莫沙拉坦(MOX)、头孢哌酮/舒巴坦(CFZ/SBT)对血液细菌耐药调查协作系统分离的超广谱β-内酰胺酶(ESBL)产生菌的最佳剂量。药代动力学参数由健康人的数据获得，目标达标率(PTA)和累积有效率(CFR)%FT>；MIC值由MCS估计。结果：从血液感染患者中共分离到2032株产ESBL的大肠埃希菌(875株)和肺炎克雷伯菌(157株产ESBL)，以及371株其他肠杆菌科细菌。对产超广谱β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌的MIC90值分别为/mg/L、2/32 mg/L和/128 mg/L。常规剂量的MOX和CFZ/SBT对MICs>；=8 mg/L和>；=4 mg/L的菌株达不到90%的PTA。对于产ESBL菌，FEP和CFZ/SBT均未达到90%CFR，而MOX(1g iv q6h、2g iv q12h和2g iv q8h)对产ESBL的大肠埃希菌的CFR均超过90%。对不产ESBL的肠杆菌科细菌，FEP和MOX的模拟CFR相似(>；90%)，高于CFZ/SBT。结论：BSI产ESBL菌对MOX高度敏感，在常规给药方案下，MOX的PTA值普遍高于FEP或CFZ/SBT。这一大型MCS分析表明，MOX而不是FEP或CFZ/SBT可以经验性地用于治疗由产ESBL的大肠杆菌菌株引起的BSI。
Objectives: Monte Carlo simulation (MCS) was used to evaluate optimal dosage for cefepime (FEP), moxalactam (MOX), and cefperazone/sulbactam (CFZ/SBT) against extended-spectrum beta-lactamase (ESBL) producers isolated from the Blood Bacterial Resistant Investigation Collaborative System.Methods: Minimum inhibitory concentration (MIC) was tested by agar dilution, and ESBL producers were identified by modified Clinical and Laboratory Standards Institute tests. Pharmacokinetic parameters were derived from data on healthy individuals, and probability of target attainment (PTA) and cumulative fraction of response (CFR) %fT >MIC values were estimated by MCS.Results: A total of 2032 Escherichia coli (875 ESBL-producing) and Klebsiella pneumoniae (157 ESBL-producing) strains, and 371 other Enterobacteriaceae strains, were isolated from patients with bloodstream infections (BSIs). MIC90 values for FEP, MOX, and CFZ/SBT against ESBL-producing E. coli and K. pneumoniae were 64/64 mg/L, 2/32 mg/L, and 64/128 mg/L, respectively. Conventional MOX and CFZ/SBT doses failed to reach 90% PTA against isolates with MICs >= 8 mg/L and >= 4 mg/L, respectively. Against ESBL producers, neither FEP nor CFZ/SBT achieved >= 90% CFR, while CFRs for MOX (1 g iv q6h, 2 g iv q12h, and 2 g iv q8h) exceeded 90% against ESBL-producing E. coli. Simulated CFRs for FEP and MOX were similar (> 90%) against non-ESBL-producing Enterobacteriaceae, and higher than CFRs for CFZ/SBT.Conclusion: ESBL producers from BSIs were highly susceptible to MOX, and PTA values were generally higher for MOX than FEP or CFZ/SBT for conventional dosing regimens. This large MCS analysis shows that MOX but not FEP or CFZ/SBT can be used empirically to treat BSIs caused by ESBL-producing E. coli strains.