Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing
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 infec...
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creator | Pragasam, Agila Kumari Jennifer, S.Lydia Solaimalai, Dhanalakshmi Muthuirulandi Sethuvel, Dhiviya Prabaa Rachel, Tanya Elangovan, Divyaa Vasudevan, Karthick Gunasekaran, Karthick Veeraraghavan, Balaji |
description | 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. blaNDM, blaOxa-48-like and blaOxa-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. |
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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. blaNDM, blaOxa-48-like and blaOxa-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.</description><identifier>ISSN: 0255-0857</identifier><identifier>EISSN: 1998-3646</identifier><identifier>DOI: 10.4103/ijmm.IJMM_20_384</identifier><identifier>PMID: 33154241</identifier><language>eng</language><publisher>United States: Elsevier B.V</publisher><subject>16S rRNA methyl transferases ; Acinetobacter baumannii - drug effects ; Acinetobacter baumannii - genetics ; Acinetobacter baumannii - isolation & purification ; aminoglycoside-modifying enzymes ; Aminoglycosides ; Aminoglycosides - metabolism ; Aminoglycosides - pharmacology ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Antimicrobial resistance ; Bacteria ; Bacterial Proteins - metabolism ; beta-Lactamases - metabolism ; Carbapenemase ; carbapenemases ; Clinical isolates ; Colistin ; Drug Resistance, Bacterial ; E coli ; Epidemiology ; Escherichia coli - drug effects ; Escherichia coli - genetics ; Escherichia coli - isolation & purification ; Gene sequencing ; Genomes ; Gram-Negative Bacteria - drug effects ; Gram-Negative Bacteria - genetics ; Gram-Negative Bacteria - isolation & purification ; Humans ; India ; Klebsiella ; Klebsiella pneumoniae ; Klebsiella pneumoniae - drug effects ; Klebsiella pneumoniae - genetics ; Klebsiella pneumoniae - isolation & purification ; Methyltransferases - genetics ; Methyltransferases - metabolism ; plazomicin ; RNA, Ribosomal, 16S ; rRNA 16S ; Sisomicin - analogs & derivatives ; Sisomicin - pharmacology ; susceptibility ; Urinary tract ; Whole Genome Sequencing</subject><ispartof>Indian journal of medical microbiology, 2020-07, Vol.38 (3-4), p.313-318</ispartof><rights>2020 Indian Journal of Medical Microbiology</rights><rights>2020. This article is published under (http://creativecommons.org/licenses/by-nc-sa/3.0/) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c394d-60dbb3599d58b9f4fe48227dd54c2f5d7e2893ff516376ee81a4b33d5dc68fc13</citedby><cites>FETCH-LOGICAL-c394d-60dbb3599d58b9f4fe48227dd54c2f5d7e2893ff516376ee81a4b33d5dc68fc13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2532569985?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,27903,27904,64362,64366,72216</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33154241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pragasam, Agila Kumari</creatorcontrib><creatorcontrib>Jennifer, S.Lydia</creatorcontrib><creatorcontrib>Solaimalai, Dhanalakshmi</creatorcontrib><creatorcontrib>Muthuirulandi Sethuvel, Dhiviya Prabaa</creatorcontrib><creatorcontrib>Rachel, Tanya</creatorcontrib><creatorcontrib>Elangovan, Divyaa</creatorcontrib><creatorcontrib>Vasudevan, Karthick</creatorcontrib><creatorcontrib>Gunasekaran, Karthick</creatorcontrib><creatorcontrib>Veeraraghavan, Balaji</creatorcontrib><title>Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing</title><title>Indian journal of medical microbiology</title><addtitle>Indian J Med Microbiol</addtitle><description>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. blaNDM, blaOxa-48-like and blaOxa-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.</description><subject>16S rRNA methyl transferases</subject><subject>Acinetobacter baumannii - drug effects</subject><subject>Acinetobacter baumannii - genetics</subject><subject>Acinetobacter baumannii - isolation & purification</subject><subject>aminoglycoside-modifying enzymes</subject><subject>Aminoglycosides</subject><subject>Aminoglycosides - metabolism</subject><subject>Aminoglycosides - pharmacology</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Antimicrobial resistance</subject><subject>Bacteria</subject><subject>Bacterial Proteins - metabolism</subject><subject>beta-Lactamases - metabolism</subject><subject>Carbapenemase</subject><subject>carbapenemases</subject><subject>Clinical isolates</subject><subject>Colistin</subject><subject>Drug Resistance, Bacterial</subject><subject>E coli</subject><subject>Epidemiology</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - isolation & purification</subject><subject>Gene sequencing</subject><subject>Genomes</subject><subject>Gram-Negative Bacteria - drug effects</subject><subject>Gram-Negative Bacteria - genetics</subject><subject>Gram-Negative Bacteria - isolation & purification</subject><subject>Humans</subject><subject>India</subject><subject>Klebsiella</subject><subject>Klebsiella pneumoniae</subject><subject>Klebsiella pneumoniae - drug effects</subject><subject>Klebsiella pneumoniae - genetics</subject><subject>Klebsiella pneumoniae - isolation & purification</subject><subject>Methyltransferases - genetics</subject><subject>Methyltransferases - metabolism</subject><subject>plazomicin</subject><subject>RNA, Ribosomal, 16S</subject><subject>rRNA 16S</subject><subject>Sisomicin - analogs & derivatives</subject><subject>Sisomicin - pharmacology</subject><subject>susceptibility</subject><subject>Urinary tract</subject><subject>Whole Genome Sequencing</subject><issn>0255-0857</issn><issn>1998-3646</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kUFvEzEQhS0EoqFw54Qscd6yXtubXW5tKSGooRUFcbS89uzG6doO9m5C-EX8TBwlRVx6sjzzzZvRewi9JvkZIzl9Z1bWns0_LxaiyAWt2BM0IXVdZbRk5VM0yQvOs7zi0xP0IsZVnv6sZs_RCaWEs4KRCfpz9WsNagCNb3v521ujjMN3Y1SwHkxjejPscKrMnTYSX8iYQO_wsAR8G2AjE-A6fG6N812_Uz4aDfgrRBMH6RTgBaildCbauFeZBWmzL9DJwWwA34Tu2PoAIRU0boO3-MfS95DNwHkL-A5-juDSTd1L9KyVfYRXx_cUff949e3yU3Z9M5tfnl9nitZMZ2Wum4byuta8auqWtcCqophqzZkqWq6nUFQ1bVtOSjotASoiWUOp5lqVVasIPUVvD7rr4NPuOIiVH4NLK0XBacHL5C9PVH6gVPAxBmjFOhgrw06QXOyjEftoxH_RpJE3R-GxsaD_DTxkkYCLA7D1_QAh3vfjFoJI7L3z20eFBSVUPKSYRN4fRCB5tDFpPiqTHARtQiKE9ubxE_8Cpj26JQ</recordid><startdate>202007</startdate><enddate>202007</enddate><creator>Pragasam, Agila Kumari</creator><creator>Jennifer, S.Lydia</creator><creator>Solaimalai, Dhanalakshmi</creator><creator>Muthuirulandi Sethuvel, Dhiviya Prabaa</creator><creator>Rachel, Tanya</creator><creator>Elangovan, Divyaa</creator><creator>Vasudevan, Karthick</creator><creator>Gunasekaran, Karthick</creator><creator>Veeraraghavan, Balaji</creator><general>Elsevier B.V</general><general>Wolters Kluwer India Pvt. 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genetics</topic><topic>Gram-Negative Bacteria - isolation & purification</topic><topic>Humans</topic><topic>India</topic><topic>Klebsiella</topic><topic>Klebsiella pneumoniae</topic><topic>Klebsiella pneumoniae - drug effects</topic><topic>Klebsiella pneumoniae - genetics</topic><topic>Klebsiella pneumoniae - isolation & purification</topic><topic>Methyltransferases - genetics</topic><topic>Methyltransferases - metabolism</topic><topic>plazomicin</topic><topic>RNA, Ribosomal, 16S</topic><topic>rRNA 16S</topic><topic>Sisomicin - analogs & derivatives</topic><topic>Sisomicin - pharmacology</topic><topic>susceptibility</topic><topic>Urinary tract</topic><topic>Whole Genome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pragasam, Agila Kumari</creatorcontrib><creatorcontrib>Jennifer, S.Lydia</creatorcontrib><creatorcontrib>Solaimalai, Dhanalakshmi</creatorcontrib><creatorcontrib>Muthuirulandi Sethuvel, Dhiviya Prabaa</creatorcontrib><creatorcontrib>Rachel, Tanya</creatorcontrib><creatorcontrib>Elangovan, Divyaa</creatorcontrib><creatorcontrib>Vasudevan, Karthick</creatorcontrib><creatorcontrib>Gunasekaran, Karthick</creatorcontrib><creatorcontrib>Veeraraghavan, Balaji</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Indian journal of medical microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pragasam, Agila Kumari</au><au>Jennifer, S.Lydia</au><au>Solaimalai, Dhanalakshmi</au><au>Muthuirulandi Sethuvel, Dhiviya Prabaa</au><au>Rachel, Tanya</au><au>Elangovan, Divyaa</au><au>Vasudevan, Karthick</au><au>Gunasekaran, Karthick</au><au>Veeraraghavan, Balaji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing</atitle><jtitle>Indian journal of medical microbiology</jtitle><addtitle>Indian J Med Microbiol</addtitle><date>2020-07</date><risdate>2020</risdate><volume>38</volume><issue>3-4</issue><spage>313</spage><epage>318</epage><pages>313-318</pages><issn>0255-0857</issn><eissn>1998-3646</eissn><abstract>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. blaNDM, blaOxa-48-like and blaOxa-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.</abstract><cop>United States</cop><pub>Elsevier B.V</pub><pmid>33154241</pmid><doi>10.4103/ijmm.IJMM_20_384</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 16S rRNA methyl transferases Acinetobacter baumannii - drug effects Acinetobacter baumannii - genetics Acinetobacter baumannii - isolation & purification aminoglycoside-modifying enzymes Aminoglycosides Aminoglycosides - metabolism Aminoglycosides - pharmacology Anti-Bacterial Agents - pharmacology Antibiotics Antimicrobial resistance Bacteria Bacterial Proteins - metabolism beta-Lactamases - metabolism Carbapenemase carbapenemases Clinical isolates Colistin Drug Resistance, Bacterial E coli Epidemiology Escherichia coli - drug effects Escherichia coli - genetics Escherichia coli - isolation & purification Gene sequencing Genomes Gram-Negative Bacteria - drug effects Gram-Negative Bacteria - genetics Gram-Negative Bacteria - isolation & purification Humans India Klebsiella Klebsiella pneumoniae Klebsiella pneumoniae - drug effects Klebsiella pneumoniae - genetics Klebsiella pneumoniae - isolation & purification Methyltransferases - genetics Methyltransferases - metabolism plazomicin RNA, Ribosomal, 16S rRNA 16S Sisomicin - analogs & derivatives Sisomicin - pharmacology susceptibility Urinary tract Whole Genome Sequencing |
title | Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing |
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