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Defining Extended Spectrum β-Lactamases: Implications of Minimum Inhibitory Concentration-Based Screening Versus Clavulanate Confirmation Testing

机译:定义扩展频谱的β-内酰胺酶:最小抑制浓度为基础的筛查与克拉维酸确认试验的意义

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Introduction While the Clinical and Laboratory Standards Institute (CLSI) recommends against routine screening for extended spectrum β-lactamases (ESBLs), knowledge of these data can provide valuable insights regarding epidemiology and drug therapy decisions. The purpose of this study was to compare the impact of minimum inhibitory concentration (MIC)-based screening versus phenotypic confirmatory testing of ESBLs on the susceptibility profile of selected antimicrobials. Methods Broth microdilution MICs were determined for various antimicrobial agents against a collection contemporary clinical Escherichia coli and Klebsiella pneumoniae isolates. Isolates identified as ESBL-positive by MIC screening were then subjected to confirmatory phenotypic testing. Percent susceptibility was based on CLSI or United States Food and Drug Administration breakpoints. Results Four-hundred and forty-two (18%) isolates screened positive for ESBL production. Of these, 274 (62%) were confirmed positive for ESBL production; 28 (10%) were also carbapenem non-susceptible. We found an under-prediction of activity for ceftolozane/tazobactam (C/T), ertapenem (ETP), meropenem (MEM), and piperacillin/tazobactam (TZP) when considering only the screen-positive testing. Conclusion For agents with potential activity against ESBLs such as C/T, TZP, ETP, and MEM, reduced susceptibility was noted when only considering the MIC screen-positive test. Although phenotypic screening selects for resistant organisms, inclusion of other genotypes besides ESBL (i.e., AmpC, carbapenemase) may falsely under-predict the potency against some ESBL producers and may limit applicability of surveillance data to geographic areas not plagued with carbapenemase producers. Funding Cubist Pharmaceuticals.
机译:简介尽管临床和实验室标准协会(CLSI)建议不要对超广谱β-内酰胺酶(ESBLs)进行常规筛查,但对这些数据的了解可以提供有关流行病学和药物治疗决策的宝贵见解。这项研究的目的是比较基于最小抑菌浓度(MIC)的筛查与ESBLs表型确证试验对所选抗菌药物敏感性的影响。方法测定肉汤微量稀释MICs,以测定针对一系列现代临床大肠杆菌和肺炎克雷伯菌分离株的抗菌剂。然后将通过MIC筛选鉴定为ESBL阳性的分离株进行验证性表型测试。敏感性百分比基于CLSI或美国食品和药物管理局的断点。结果420株(18%)分离株筛选出ESBL阳性。其中,274(62%)个被确认对ESBL产生阳性; 28例(10%)也是不敏感的碳青霉烯。当仅考虑筛查阳性试验时,我们发现对头孢洛赞/他唑巴坦(C / T),厄他培南(ETP),美罗培南(MEM)和哌拉西林/他唑巴坦(TZP)的活性预测不足。结论对于具有抗ESBLs潜在活性的药物,例如C / T,TZP,ETP和MEM,仅考虑MIC筛查阳性试验时,药敏性降低。尽管表型筛选选择了抗药性生物,但除ESBL之外还包括其他基因型(即AmpC,碳青霉烯酶)可能会错误地低估了某些ESBL生产者的效力,并且可能会将监测数据的适用范围限制在不受碳青霉烯酶生产者困扰的地理区域。资助立体主义制药。

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