Infectious Diseases Department, National Institute of Health Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal.
Microbiol Spectr. 2023 Aug 17;11(4):e0107023. doi: 10.1128/spectrum.01070-23. Epub 2023 Jun 26.
We present two independent cases of recurrent multidrug-resistant Campylobacter jejuni infection in immunocompromised hosts and the clinical challenges encountered due to the development of high-level carbapenem resistance. The mechanisms associated with this unusual resistance for were characterized. Initial macrolide and carbapenem-susceptible strains acquired resistance to erythromycin (MIC > 256mg/L), ertapenem (MIC > 32mg/L), and meropenem (MIC > 32mg/L) during treatment. Carbapenem-resistant isolates developed an in-frame insertion resulting in an extra Asp residue in the major outer membrane protein PorA, within the extracellular loop L3 that connects β-strands 5 and 6 and forms a constriction zone involved in Ca binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167A|Gly56Asp) at PorA's extracellular loop L1. Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within A. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.
我们报告了两例免疫功能低下宿主中复发性多药耐药空肠弯曲菌感染的独立病例，以及由于高水平碳青霉烯耐药性的发展而出现的临床挑战。对这种不寻常耐药性的相关机制进行了表征。初始对大环内酯类和碳青霉烯类敏感的菌株在治疗过程中对红霉素（MIC > 256mg/L）、厄他培南（MIC > 32mg/L）和美罗培南（MIC > 32mg/L）产生耐药性。耐碳青霉烯类的分离株在主要外膜蛋白 PorA 的细胞外环 L3 中发生了无义突变，导致额外的 Asp 残基插入，该区域连接β-5 和β-6 链并形成一个参与 Ca 结合的紧缩区。对厄他培南表现出最高 MIC 的分离株在 PorA 的细胞外环 L1 中存在额外的非同义突变（G167A|Gly56Asp）。碳青霉烯类药物的药敏模式提示药物渗透性差，与插入和/或 A 内的单核苷酸多态性（SNP）有关。在两个独立病例中发生的类似分子事件支持这些机制与弯曲菌属中碳青霉烯类耐药性的相关性。
