Background: Aminoglycoside resistance is a growing challenge, and it is commonly mediated by the aminoglycoside-modifying enzymes (AMEs), followed by 16S rRNA methyl transferase. Plazomicin, a novel aminoglycoside agent approved by the Food and Drug Administration for complicated urinary tract infections is proven to overcome resistance mediated by AMEs but not due to 16S rRNA methyl transferase (16SRMTases). We undertook this study to predict the efficacy of plazomicin in India based on the antimicrobial resistance profile derived from whole-genome sequencing (WGS). Methodology: A total of 386 clinical isolates of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii subjected to WGS were screened for aminoglycoside-resistance mechanisms such as AMEs and 16SRMTases and its association with carbapenemases. Results: AMEs was present in all E. coli, A. baumannii and in 90% of K. pneumoniae. In addition, up to 47% of E. coli and 38% of K. pneumoniae co-carried 16SRMTases with AMEs genes. However, A. baumannii showed 87% of isolates co-harbouring 16SRMTase. bla NDM, bla Oxa-48-like and bla Oxa-23-like were the most predominant carbapenemases in E. coli, K. pneumoniae and A. baumannii, respectively. Notably, 48% of NDM-producing E. coli and 35% of Oxa-48-like producing K. pneumoniae were identified to co-harbour AMEs + RMTAses, where plazomicin may not be useful. Conclusion: Overall, 53%, 62% and 14% of carbapenemase-producing E. coli, K. pneumoniae and A. baumannii harbours only AMEs, indicating the role of plazomicin use. Plazomicin can be used both for ESBLs as “carbapenem-sparing agent” and carbapenemase producers as “colistin-sparing agent.” For optimal use, it is essential to know the molecular epidemiology of resistance in a given geographical region where plazomicin empirical therapy is considered.


中文翻译：

---

根据全基因组测序得出的革兰氏阴性生物体中普遍存在的氨基糖苷类耐药机制，预计印度对普拉佐米星的敏感性



背景：氨基糖苷类耐药性是一个日益严峻的挑战，它通常由氨基糖苷类修饰酶 (AME) 介导，其次是 16S rRNA 甲基转移酶。 Plazomicin 是美国食品和药物管理局批准用于治疗复杂尿路感染的新型氨基糖苷类药物，已被证明可以克服 AME 介导的耐药性，但不能克服 16S rRNA 甲基转移酶 (16SRMTases) 介导的耐药性。我们开展这项研究的目的是根据全基因组测序 (WGS) 得出的抗菌药物耐药性概况来预测普拉佐米星在印度的疗效。方法：对总共 386 株大肠杆菌、肺炎克雷伯菌和鲍曼不动杆菌临床分离株进行全基因组测序，筛选其氨基糖苷类耐药机制，如 AME 和 16SRMTase 及其与碳青霉烯酶的关联。结果： AME 存在于所有大肠杆菌、鲍曼不动杆菌和 90% 的肺炎克雷伯菌中。此外，高达 47% 的大肠杆菌和 38% 的肺炎克雷伯菌同时携带 16 个 SRMTase 和 AME 基因。然而，鲍曼不动杆菌显示 87% 的分离株共同携带 16SRMTase。 bla NDM、 bla Oxa-48 样和bla Oxa-23 样是大肠杆菌、K中最主要的碳青霉烯酶。肺炎杆菌和A .分别是鲍曼不动杆菌。值得注意的是，48% 的产生 NDM 的大肠杆菌和 35% 的产生 Oxa-48 样的肺炎克雷伯菌被鉴定为共同携带 AME + RMTAses，而普拉佐米星在这些情况下可能不起作用。结论：总体而言，产碳青霉烯酶的大肠杆菌、肺炎克雷伯菌和曲霉分别为 53%、62% 和 14%。 鲍曼不动杆菌仅含有 AME，表明使用 plazomicin 的作用。 Plazomicin 既可用作 ESBL 的“碳青霉烯类节约剂”，也可用作碳青霉烯酶生产者的“粘菌素节约剂”。为了获得最佳使用效果，有必要了解考虑使用普拉佐米星经验治疗的特定地理区域的耐药性分子流行病学。