Ransom Eric, Bhatnagar Amelia, Patel Jean B, Machado Maria-Jose, Boyd Sandra, Reese Natashia, Lutgring Joseph D, Lonsway David, Anderson Karen, Brown Allison C, Elkins Christopher A, Rasheed J Kamile, Karlsson Maria
Association of Public Health Laboratories, Silver Spring, Maryland, USA.
Eagle Medical Services, LLC, Atlanta, Georgia, USA.
J Clin Microbiol. 2020 Mar 25;58(4). doi: 10.1128/JCM.01944-19.
Aztreonam-avibactam is a combination antimicrobial agent with activity against carbapenemase-producing (CPE) with metallo-β-lactamases (MβLs). Although aztreonam-avibactam is not yet approved by the U.S. Food and Drug Administration (FDA), clinicians can administer this combination by using two FDA-approved drugs: aztreonam and ceftazidime-avibactam. This combination of drugs is recommended by multiple experts for treatment of serious infections caused by MβL-producing CPE. At present, antimicrobial susceptibility testing (AST) of aztreonam-avibactam is not commercially available; thus, most clinicians receive no laboratory-based guidance that can support consideration of aztreonam-avibactam for serious CPE infections. Here, we report our internal validation for aztreonam-avibactam AST by reference broth microdilution (BMD) according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The validation was performed using custom frozen reference BMD panels prepared in-house at the Centers for Disease Control and Prevention (CDC). In addition, we took this opportunity to evaluate a new panel-making method using a digital dispenser, the Hewlett Packard (HP) D300e. Our studies demonstrate that the performance characteristics of digitally dispensed panels were equivalent to those of conventionally prepared frozen reference BMD panels for a number of drugs, including aztreonam-avibactam. We found the HP D300e digital dispenser to be easy to use and to provide the capacity to prepare complex drug panels. Our findings will help other clinical and public health laboratories implement susceptibility testing for aztreonam-avibactam.
阿曲南-阿维巴坦是一种联合抗菌药物，对产金属β-内酰胺酶（MβL）的碳青霉烯酶产生菌（CPE）具有活性。尽管阿曲南-阿维巴坦尚未获得美国食品药品监督管理局（FDA）的批准，但临床医生可以通过使用两种FDA批准的药物来使用这种联合用药：阿曲南和头孢他啶-阿维巴坦。多位专家推荐这种联合用药用于治疗由产MβL的CPE引起的严重感染。目前，阿曲南-阿维巴坦的抗菌药敏试验（AST）尚无商业可用产品；因此，大多数临床医生得不到基于实验室的指导来支持考虑将阿曲南-阿维巴坦用于治疗严重的CPE感染。在此，我们报告根据临床和实验室标准协会（CLSI）指南通过参考肉汤微量稀释法（BMD）对阿曲南-阿维巴坦进行AST的内部验证。验证使用疾病控制与预防中心（CDC）内部制备的定制冷冻参考BMD板进行。此外，我们借此机会评估了一种使用数字分配器惠普（HP）D300e的新板制备方法。我们的研究表明对于包括阿曲南-阿维巴坦在内的多种药物，数字分配板的性能特征与传统制备的冷冻参考BMD板相当。我们发现惠普D300e数字分配器易于使用，并具备制备复杂药物板的能力。我们的研究结果将有助于其他临床和公共卫生实验室开展阿曲南-阿维巴坦的药敏试验。
