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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Veröffentlicht in:Indian journal of medical microbiology 2020-07, Vol.38 (3-4), p.313-318
Hauptverfasser: Pragasam, Agila Kumari, Jennifer, S.Lydia, Solaimalai, Dhanalakshmi, Muthuirulandi Sethuvel, Dhiviya Prabaa, Rachel, Tanya, Elangovan, Divyaa, Vasudevan, Karthick, Gunasekaran, Karthick, Veeraraghavan, Balaji
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container_end_page 318
container_issue 3-4
container_start_page 313
container_title Indian journal of medical microbiology
container_volume 38
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.
doi_str_mv 10.4103/ijmm.IJMM_20_384
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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. 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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. 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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.</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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ispartof Indian journal of medical microbiology, 2020-07, Vol.38 (3-4), p.313-318
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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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