Kon Hadas, Lurie-Weinberger Mor N, Bechor Moshe, Temkin Elizabeth, Kastel Ophir, Schwartz David, Keren-Paz Alona, Carmeli Yehuda
National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Antimicrob Agents Chemother. 2024 Dec 5;68(12):e0096524. doi: 10.1128/aac.00965-24. Epub 2024 Oct 31.
Carbapenem-resistant (CRPA) are of major clinical concern. We analyzed 85 . blood isolates non-susceptible to carbapenems collected during 2021-2023 from 15 medical centers in Israel. We aimed to determine the prevalence of high-risk clones, examine clonality, test antibiotic susceptibility, and assess the presence of acquired resistance genes, including carbapenemases. Whole-genome sequencing was performed using Illumina sequencing technology. Susceptibly was determined using the broth microdilution method. In the entire sample, 43.5% were high-risk clones. A main clade (27.1% of isolates) found in multiple hospitals comprised 19 isolates belonging to the high-risk ST654 clone and four closely related isolates. The isolates in this main clade harbored a broad set of resistance genes, including GES-type genes, and 91% had a mutated outer membrane protein (OprD). Isolates in the main clade were uniformly tobramycin (TOB) resistant and 83% were ceftolozane/tazobactam resistant. In the entire sample, we found high resistance to most antipseudomonal agents, including new beta-lactam/beta-lactamase inhibitor combinations. No uniform susceptibility to an antipseudomonal agent was found. Carbapenemases were carried by 9.4% of isolates (5.9% and 3.5% ) and was mutated in 67% of isolates. Thus, the epidemiology of CRPA is explained by a combination of clonal expansion of a dominant high-risk clade and sporadic occurrence of mutated strains. Our findings highlight the importance of susceptibility testing using a wide panel of antibiotics when CRPA is detected. Prevention measures tracking and controlling emerging high-risk clades and clones are crucial to limit the spread of CRPA.
耐碳青霉烯类（CRPA）是主要的临床关注对象。我们分析了2021年至2023年期间从以色列15个医疗中心收集的85株对碳青霉烯类不敏感的血液分离株。我们旨在确定高危克隆的流行情况，检查克隆性，测试抗生素敏感性，并评估获得性耐药基因（包括碳青霉烯酶）的存在情况。使用Illumina测序技术进行全基因组测序。使用肉汤微量稀释法确定敏感性。在整个样本中，43.5%为高危克隆。在多家医院发现的一个主要分支（占分离株的27.1%）包括19株属于高危ST654克隆的分离株和4株密切相关的分离株。这个主要分支中的分离株携带了广泛的耐药基因，包括GES型基因，91%的分离株外膜蛋白（OprD）发生了突变。主要分支中的分离株对妥布霉素（TOB）均耐药，83%对头孢洛扎/他唑巴坦耐药。在整个样本中，我们发现对大多数抗假单胞菌药物具有高度耐药性，包括新型β-内酰胺/β-内酰胺酶抑制剂组合。未发现对某一种抗假单胞菌药物有一致的敏感性。9.4%的分离株携带碳青霉烯酶（5.9%和3.5%），67%的分离株发生了突变。因此，CRPA的流行病学可以通过一个占主导地位的高危分支的克隆性扩张和突变菌株的散发性出现来解释。我们的研究结果强调了在检测到CRPA时使用多种抗生素进行敏感性测试的重要性。追踪和控制新兴高危分支和克隆的预防措施对于限制CRPA的传播至关重要。
