Pragasam Agila Kumari, Jennifer S Lydia, Solaimalai Dhanalakshmi, Muthuirulandi Sethuvel Dhiviya Prabaa, Rachel Tanya, Elangovan Divyaa, Vasudevan Karthick, Gunasekaran Karthick, Veeraraghavan Balaji
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.
Department of General Medicine (Unit.V), Christian Medical College, Vellore, Tamil Nadu, India.
Indian J Med Microbiol. 2020 Jul-Dec;38(3 & 4):313-318. doi: 10.4103/ijmm.IJMM_20_384.
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).
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.
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.
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.
氨基糖苷类耐药性是一个日益严峻的挑战，其通常由氨基糖苷类修饰酶（AMEs）介导，其次是16S rRNA甲基转移酶。普拉佐米星是一种经美国食品药品监督管理局批准用于治疗复杂性尿路感染的新型氨基糖苷类药物，已被证明可克服由AMEs介导的耐药性，但对由16S rRNA甲基转移酶（16SRMTases）介导的耐药性无效。我们开展这项研究，旨在根据全基因组测序（WGS）得出的抗菌药物耐药谱预测普拉佐米星在印度的疗效。
对386株经WGS检测的大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌临床分离株进行筛选，以确定其氨基糖苷类耐药机制，如AMEs和16SRMTases及其与碳青霉烯酶的关联。
AMEs存在于所有大肠埃希菌、鲍曼不动杆菌以及90%的肺炎克雷伯菌中。此外，高达47%的大肠埃希菌和38%的肺炎克雷伯菌同时携带16SRMTases和AMEs基因。然而，鲍曼不动杆菌中87%的分离株同时携带16SRMTase。bla NDM、bla Oxa - 48样和bla Oxa - 23样分别是大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌中最主要的碳青霉烯酶。值得注意的是，48%产NDM的大肠埃希菌和35%产Oxa - 48样的肺炎克雷伯菌被鉴定为同时携带AMEs + RMTAses，在这些情况下普拉佐米星可能无效。
总体而言，产碳青霉烯酶的大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌中分别有53%、62%和14%仅携带AMEs，这表明了普拉佐米星的应用价值。普拉佐米星既可以作为“碳青霉烯类药物节省剂”用于产ESBLs菌株，也可以作为“黏菌素节省剂”用于产碳青霉烯酶菌株。为了实现最佳应用，了解在考虑使用普拉佐米星经验性治疗的特定地理区域内的耐药分子流行病学情况至关重要。
