Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA; Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA.
Int J Antimicrob Agents. 2018 Nov;52(5):688-691. doi: 10.1016/j.ijantimicag.2018.07.011. Epub 2018 Jul 22.
Ceftazidime/avibactam plus aztreonam (CZA+ATM) is an emerging option to combat carbapenemase-producing Enterobacteriaceae (CPE) expressing resistance via multiple β-lactamases within Ambler classes A, B, C, and D. The benefit of this combination is apparent when the pathogen-specific resistance genotype is characterized. However, rapid molecular diagnostic systems may be unavailable to allow this precision medicine-based approach. Using synergy tests with antibiotic gradient diffusion strips (GDSs), we aimed to prove that the defined phenotypic profile of CPE is reliably predicted by the genotype to confirm the utility of this method as a phenotypic profiling tool for use in the clinical setting. Synergy assessments for CPE (n=10) that co-produce serine- and metallo-β-lactamases were performed by crossing CZA and ATM antibiotic GDSs (Liofilchem and Etest). The minimum inhibitory concentration (MIC):MIC ratio method was also conducted for five CPE. All CPE were resistant to CZA and ATM when tested alone. Using classical fractional inhibitory concentration definitions, synergy (9/10) and additivity (1/10) was detected by at least one method for all isolates. As predicted by cross-coverage of genotypically defined serine- and metallo-β-lactamases, for all isolates CZA+ATM produced a phenotypic profile distinguished by sizeable zones of inhibited growth which we term the 'zone of hope'. In conclusion, simple procedures utilizing antibiotic GDSs were concordant with the known genotypic profile of the CPE selected for study. This approach appears to be a valuable tool for guiding therapy in the absence of molecular diagnostic systems. Furthermore, this study confirms potent in vitro activity of CZA+ATM against CPE expressing multiple β-lactamases.
头孢他啶/阿维巴坦联合氨曲南（CZA+ATM）是一种针对产碳青霉烯酶肠杆菌科细菌（CPE）的新兴治疗选择，这些细菌通过 Ambler 分类 A、B、C 和 D 中的多种β-内酰胺酶表达耐药性。当明确病原体的耐药基因型时，这种联合用药的优势就显而易见了。然而，可能无法获得快速的分子诊断系统来支持这种精准医学方法。本研究通过抗生素梯度扩散条（GDS）协同试验，旨在证明 CPE 的明确表型特征可通过基因型可靠预测，从而证实该方法可作为一种表型分析工具，用于临床环境。通过交叉 CZA 和 ATM 抗生素 GDS（Liofilchem 和 Etest）对同时产生丝氨酸酶和金属酶的 CPE（n=10）进行协同评估。还对 5 株 CPE 进行了最低抑菌浓度（MIC）：MIC 比值法检测。单独测试时，所有 CPE 对 CZA 和 ATM 均耐药。所有分离株均通过至少一种方法检测到协同作用（9/10）和相加作用（1/10），根据经典的部分抑菌浓度定义。根据基因型定义的丝氨酸酶和金属酶的交叉覆盖预测，所有分离株的 CZA+ATM 均产生了表型特征，表现为明显的抑菌生长区，我们将其称为“希望区”。总之，利用抗生素 GDS 的简单程序与所选 CPE 的已知基因型谱一致。在缺乏分子诊断系统的情况下，这种方法似乎是指导治疗的有价值工具。此外，本研究证实了 CZA+ATM 对表达多种β-内酰胺酶的 CPE 具有强大的体外活性。
