摘要

本研究的目的是对来自沙特阿拉伯西部地区的产超广谱β-内酰胺酶的大肠杆菌分离株进行基因型鉴定，并利用表型和分子模型鉴定针对这些分离株的活性抗生素。总共从MALDI-TOF鉴定了从异质临床标本中回收的211株产ESBL的大肠杆菌分离物。从产ESBL的大肠杆菌的多位点序列分型（MLST）分析中鉴定出32种序列类型（ST），包括新的ST（ST8162）。沙特和外籍人口中最常见的ST是ST131，其次是ST38。所有分离株均为多药耐药（MDR），> 95％的分离株对第三代（头孢曲松和头孢他啶）和第四代（头孢吡肟）头孢菌素具有耐药性。 ESBL阳性大肠杆菌分离株主要包含blaCTX-M和blaTEM基因。对碳青霉烯类抗生素组没有观察到耐药性。观察到所有产ESBL的大肠杆菌分离株对头孢他啶/ avibactam组合敏感。对接复合物的分子相互作用分析揭示了对于抗生素和抑制剂与模拟的CTX-M-15酶结合至关重要的氨基酸残基。重要的是，avibactam在对接状态下测试的抑制剂中显示出与CTX-M-15最强的相互作用（ΔG= -6.6kcal / mol）。克拉维酸盐，他唑巴坦和舒巴坦的结合自由能值分别测定为-5.7，-5.9和-5.2kcal / mol。总体而言，该研究的结论是，“头孢他啶和avibactam”应该谨慎使用，作为一种治疗选择，仅针对该地区仅产生碳青霉烯类耐药MDR产ESBL的大肠杆菌。

The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producing Escherichia coli isolates from the western region of Saudi Arabia and to identify active antibiotics against these isolates using phenotypic and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two sequence types (STs) were identified from a multilocus sequence typing (MLST) analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most common ST in the Saudi and expatriate population was ST131, followed by ST38. All the isolates were multidrug resistant (MDR), and >95% of the isolates were resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored the blaCTX-M and blaTEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producing E. coli isolates were observed to be susceptible to a ceftazidime/avibactam combination. Molecular interaction analyses of the docked complexes revealed the amino acid residues crucial for the binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme. Importantly, avibactam displayed the most robust interaction with CTX-M-15 among the tested inhibitors in the docked state (∆G = -6.6 kcal/mol). The binding free energy values for clavulanate, tazobactam and sulbactam were determined to be -5.7, -5.9 and -5.2 kcal/mol, respectively. Overall, the study concludes that 'ceftazidime along with avibactam' should be carefully used as a treatment option against only carbapenem-resistant MDR ESBL-producing E. coli in this region.

https://www.ncbi.nlm.nih.gov/pubmed/30287889