In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates

ABSTRACT: Objectives: Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of...

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Main Authors: François Caméléna, Mathilde Liberge, Inès Rezzoug, Manel Merimèche, Thierry Naas, Béatrice Berçot
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Journal of Global Antimicrobial Resistance
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213716523000188
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author François Caméléna
Mathilde Liberge
Inès Rezzoug
Manel Merimèche
Thierry Naas
Béatrice Berçot
author_facet François Caméléna
Mathilde Liberge
Inès Rezzoug
Manel Merimèche
Thierry Naas
Béatrice Berçot
author_sort François Caméléna
collection DOAJ
description ABSTRACT: Objectives: Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of 16S-RMTase-producing isolates, including Enterobacterales, non-fermenting bacteria, and carbapenemase producers. Methods: In total, 164 non-duplicate 16S-RMTase-producing isolates, including 84 Enterobacterales, 53 Acinetobacter baumannii and 27 Pseudomonas aeruginosa isolates, were included in the study. Whole-genome sequencing (WGS) was performed on all isolates with Illumina technology. The minimum inhibitory concentration (MIC) of apramycin was determined by broth microdilution with customized Sensititre plates (Thermo Fisher Scientific, Dardilly, France). Results: We found that 95% (156/164) of the 16S-RMTase-producing isolates were susceptible to apramycin, with a MIC50 of 4 mg/L and a MIC90 of 16 mg/L, respectively. Resistance rates were higher in P. aeruginosa (11%) than in A. baumannii (4%) or Enterobacterales (4%) (P < 0.0001 for each comparison). Eight isolates were resistant to apramycin, including one isolate with an MIC >64 mg/L due to the acquisition of the aac(3)-IV gene. The genetic environment of the aac(3)-IV gene was similar to that in the pAH01–4 plasmid of an Escherichia coli isolate from chicken in China. Conclusion: Resistance to apramycin remains rare in 16S-RMTase-producing isolates. Apramycin may, therefore, be an interesting alternative treatment for infections caused by 16S-RMTase and carbapenemase producers.
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spelling doaj.art-dbecf7408002454596a446604af453bd2023-06-17T05:18:23ZengElsevierJournal of Global Antimicrobial Resistance2213-71652023-06-01332125In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolatesFrançois Caméléna0Mathilde Liberge1Inès Rezzoug2Manel Merimèche3Thierry Naas4Béatrice Berçot5Department of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, FranceDepartment of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, FranceDepartment of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, FranceDepartment of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, FranceDepartment of Bacteriology-Hygiene, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Université de Paris-Saclay, INSERM 1184, RESIST Unit, Le Kremlin-Bicêtre, France; French National Reference Centre for Antimicrobial Resistance, Le Kremlin-Bicêtre, FranceDepartment of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, France; Corresponding author. Department of Bacteriology, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, 1 av. Claude Vellefaux 75010 Paris, FranceABSTRACT: Objectives: Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of 16S-RMTase-producing isolates, including Enterobacterales, non-fermenting bacteria, and carbapenemase producers. Methods: In total, 164 non-duplicate 16S-RMTase-producing isolates, including 84 Enterobacterales, 53 Acinetobacter baumannii and 27 Pseudomonas aeruginosa isolates, were included in the study. Whole-genome sequencing (WGS) was performed on all isolates with Illumina technology. The minimum inhibitory concentration (MIC) of apramycin was determined by broth microdilution with customized Sensititre plates (Thermo Fisher Scientific, Dardilly, France). Results: We found that 95% (156/164) of the 16S-RMTase-producing isolates were susceptible to apramycin, with a MIC50 of 4 mg/L and a MIC90 of 16 mg/L, respectively. Resistance rates were higher in P. aeruginosa (11%) than in A. baumannii (4%) or Enterobacterales (4%) (P < 0.0001 for each comparison). Eight isolates were resistant to apramycin, including one isolate with an MIC >64 mg/L due to the acquisition of the aac(3)-IV gene. The genetic environment of the aac(3)-IV gene was similar to that in the pAH01–4 plasmid of an Escherichia coli isolate from chicken in China. Conclusion: Resistance to apramycin remains rare in 16S-RMTase-producing isolates. Apramycin may, therefore, be an interesting alternative treatment for infections caused by 16S-RMTase and carbapenemase producers.http://www.sciencedirect.com/science/article/pii/S2213716523000188Aminoglycosides16S rRNA methyltransferasesArmARmtBAAC(3)-IVGram-negative bacilli
spellingShingle François Caméléna
Mathilde Liberge
Inès Rezzoug
Manel Merimèche
Thierry Naas
Béatrice Berçot
In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
Journal of Global Antimicrobial Resistance
Aminoglycosides
16S rRNA methyltransferases
ArmA
RmtB
AAC(3)-IV
Gram-negative bacilli
title In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
title_full In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
title_fullStr In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
title_full_unstemmed In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
title_short In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
title_sort in vitro activity of apramycin against 16s rmtase producing gram negative isolates
topic Aminoglycosides
16S rRNA methyltransferases
ArmA
RmtB
AAC(3)-IV
Gram-negative bacilli
url http://www.sciencedirect.com/science/article/pii/S2213716523000188
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