Cartagena Alexis Jaramillo, Taylor Kyra L, Smith Joshua T, Manson Abigail L, Pierce Virginia M, Earl Ashlee M, Bhattacharyya Roby P
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Microbiology Laboratory, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
bioRxiv. 2023 Oct 4:2023.05.23.541813. doi: 10.1101/2023.05.23.541813.
Carbapenem-resistant (CRE) are important pathogens that can develop resistance via multiple molecular mechanisms, including hydrolysis or reduced antibiotic influx. Identifying these mechanisms can improve pathogen surveillance, infection control, and patient care. We investigated how resistance mechanisms influence the carbapenem inoculum effect (IE), a phenomenon where inoculum size affects antimicrobial susceptibility testing (AST). We demonstrated that seven different carbapenemases impart a meropenem IE in . Across 110 clinical CRE isolates, the carbapenem IE strictly depended on resistance mechanism: all carbapenemase-producing CRE (CP-CRE) exhibited a strong IE, whereas porin-deficient CRE displayed none. Concerningly, 50% and 24% of CP-CRE isolates changed susceptibility classification to meropenem and ertapenem, respectively, across the allowable inoculum range in clinical guidelines. The meropenem IE, and the ratio of ertapenem to meropenem minimal inhibitory concentration (MIC) at standard inoculum, reliably identified CP-CRE. Understanding how resistance mechanisms affect AST could improve diagnosis and guide therapies for CRE infections.
耐碳青霉烯类肠杆菌科细菌（CRE）是重要的病原体，可通过多种分子机制产生耐药性，包括水解或抗生素流入减少。识别这些机制可改善病原体监测、感染控制和患者护理。我们研究了耐药机制如何影响碳青霉烯类接种物效应（IE），即接种物大小影响抗菌药物敏感性试验（AST）的现象。我们证明，七种不同的碳青霉烯酶在……中产生美罗培南IE。在110株临床CRE分离株中，碳青霉烯类IE严格取决于耐药机制：所有产碳青霉烯酶的CRE（CP-CRE）均表现出强烈的IE，而孔蛋白缺陷型CRE则未表现出IE。令人担忧的是，在临床指南允许的接种物范围内，分别有50%和24%的CP-CRE分离株对美罗培南和厄他培南的敏感性分类发生了变化。美罗培南IE以及标准接种物时厄他培南与美罗培南最低抑菌浓度（MIC）的比值能够可靠地识别CP-CRE。了解耐药机制如何影响AST可改善CRE感染的诊断并指导治疗。
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