Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Letter to the Editor

Emergence of Klebsiella pneumoniae Harboring the aac(6ʹ)-Ian Amikacin Resistance Gene

Paloma Troyano-Hernáez, Almudena Gutiérrez-Arroyo, Rosa Gómez-Gil, Jesús Mingorance, Fernando Lázaro-Perona
Paloma Troyano-Hernáez
aServicio de Microbiología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Almudena Gutiérrez-Arroyo
aServicio de Microbiología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rosa Gómez-Gil
aServicio de Microbiología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jesús Mingorance
aServicio de Microbiología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jesús Mingorance
Fernando Lázaro-Perona
aServicio de Microbiología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.01952-18
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

LETTER

Carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health concern worldwide (1). Isolates producing NDM and KPC carbapenemases often carry 16S rRNA methyltransferases (16S-RMTases) that confer resistance to several aminoglycosides (2), while OXA-48- and VIM-producing Enterobacteriaceae most often produce aminoglycoside-modifying enzymes that confer resistance to gentamicin and tobramycin but spare amikacin. In the Mediterranean region, OXA-48 and VIM are predominant, and susceptibility to amikacin remains high (>90%) (3–5).

We have recently reported pandrug resistance in a VIM-1-producing Klebsiella pneumoniae sequence type 54 (ST54) isolate obtained from a pediatric patient (6). The isolate harbored a plasmid-carried aac(6ʹ)-Ian gene coding for an aminoglycoside 6ʹ-N-acetyltransferase that conferred resistance to amikacin. The aim of this study was to investigate the presence of this gene in clinical enterobacterial isolates obtained from pediatric patients in our hospital. The study was approved by the local review board. A retrospective search for amikacin-resistant Enterobacteriaceae was done using the microbiology department database. We recovered 26 amikacin-resistant (MIC, >16 µg/ml) isolates that had been obtained between January 2010 and August 2017. The aac(6ʹ)-Ian gene was searched by PCR using primers aac(6ʹ)-Ian-F (5ʹ-GGTGCTTTATACTTCCTATA-3ʹ) and aac(6ʹ)-Ian-R (5ʹ-ATACTGATCTTCTGGAGAT-3ʹ). Thirteen isolates were positive for the gene (Table 1), and all of them were Klebsiella pneumoniae. Two ST54-specific regions were selected, and two pairs of specific primers were designed (7), as follows: St-54-c100-F (5ʹ-AACTGTTCTGTGGCTGGTCC-3ʹ) and St-54-C100-R (5ʹ-TGCCAATCCTGACGAGTCTC-3ʹ), and St-54-C40-F (5ʹ-CCGACAATGGCTGCAATCC-3ʹ) and St-54-C40-R (5ʹ-GCCTTACCGTTACGCTTCAC-3ʹ). Nine of the isolates belonged to ST54. The clonality of the four non-ST54 isolates was determined by randomly amplified polymorphic DNA (RAPD) analysis, and they were found to be different sequence types. The aac(6ʹ)-Ian gene harboring plasmid pKP1050-4 (6) was searched by PCR among these four isolates using primers targeting the IncN repE gene, Inc-N-F (5ʹ-AGCGCGTTCTCTGGTTATGT-3ʹ) and Inc-N-R (5ʹ-GGAGCGAGTAGGTGGTGAAC-3ʹ). One of the non-ST54 isolates had the same plasmid, while the other three did not.

View this table:
  • View inline
  • View popup
TABLE 1

Amikacin-resistant clinical isolates recovered from pediatric patients from 2010 to 2017

All 13 patients were in severe condition and had long hospital stays. Eight of the patients had been admitted to transplant units and had stays longer than 3 months. Ten patients had been in the pediatric intensive care unit for at least 4 weeks, and two patients had been in the neonatal intensive care unit.

The aminoglycoside acetyltransferase aac(6ʹ)-Ian gene was described in 2015 in Serratia marcescens isolates from Japan (8). We did a database search and identified 13 additional matches, with all but one being clinical isolates of human origin (Table 2). Amikacin is the aminoglycoside in clinical use that is most resistant to aminoglycoside-modifying enzymes (9), and it is used as a last-resort drug in our environment to treat severe infections and late-onset neonatal sepsis. The spread of VIM-producing strains harboring the aac(6ʹ)-Ian gene adds to that of the NDM- and KPC-producing strains harboring 16S-RMTases and might become a serious challenge for the treatment of CPE.

View this table:
  • View inline
  • View popup
TABLE 2

Results of a GenBank search using the aminoglycoside 6ʹ-N-acetyltransferase aac(6ʹ)-Ian gene sequencea

ACKNOWLEDGMENTS

This work was supported by grants PI13/01218 and PI16/01209 from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III to J.M. and cofinanced by the European Development Regional Fund, “A way to achieve Europe.”

We declare no conflicts of interest.

  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Logan LK,
    2. Weinstein RA
    . 2017. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 215:S28–S36. doi:10.1093/infdis/jiw282.
    OpenUrlCrossRef
  2. 2.↵
    1. Doi Y,
    2. Wachino J-I,
    3. Arakawa Y
    . 2016. Aminoglycoside resistance: the emergence of acquired 16S ribosomal RNA methyltransferases. Infect Dis Clin North Am 30:523–537. doi:10.1016/j.idc.2016.02.011.
    OpenUrlCrossRef
  3. 3.↵
    1. Pérez-Blanco V,
    2. Redondo-Bravo L,
    3. Ruíz-Carrascoso G,
    4. Paño-Pardo JR,
    5. Gómez-Gil R,
    6. Robustillo-Rodela A,
    7. García- Rodríguez J,
    8. Mingorance J,
    9. Herruzo R
    . 2018. Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital-wide oligoclonal outbreak. Epidemiol Infect 146:656–662. doi:10.1017/S0950268818000249.
    OpenUrlCrossRef
  4. 4.↵
    1. Hernández-García M,
    2. Pérez-Viso B,
    3. Carmen Turrientes M,
    4. Díaz-Agero C,
    5. López-Fresneña N,
    6. Bonten M,
    7. Malhotra-Kumar S,
    8. Ruiz-Garbajosa P,
    9. Cantón R
    . 2018. Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones. J Antimicrob Chemother, in press.
  5. 5.↵
    1. Potron A,
    2. Poirel L,
    3. Rondinaud E,
    4. Nordmann P
    . 2013. Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. Euro Surveill 18:pii=20549. doi:10.2807/1560-7917.ES2013.18.31.20549.
    OpenUrlCrossRef
  6. 6.↵
    1. Lázaro-Perona F,
    2. Sotillo A,
    3. Troyano-Hernáez P,
    4. Gómez-Gil R,
    5. de la Vega-Bueno Á,
    6. Mingorance J
    . 2018. Genomic path to panresistance in a clinical isolate of Klebsiella pneumoniae. Int J Antimicrob Agents, in press.
  7. 7.↵
    1. López-Camacho E,
    2. Rentero Z,
    3. Ruiz-Carrascoso G,
    4. Wesselink J-JJ-J,
    5. Pérez-Vázquez M,
    6. Lusa-Bernal S,
    7. Gómez-Puertas P,
    8. Kingsley RAA,
    9. Gómez-Sánchez P,
    10. Campos J,
    11. Oteo J,
    12. Mingorance J
    . 2014. Design of clone-specific probes from genome sequences for rapid PCR-typing of outbreak pathogens. Clin Microbiol Infect 20:O891–O893. doi:10.1111/1469-0691.12616.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Jin W,
    2. Wachino J,
    3. Kimura K,
    4. Yamada K,
    5. Arakawa Y
    . 2015. New plasmid-mediated aminoglycoside 6′-N-acetyltransferase, aac(6′)-Ian, and ESBL, TLA-3, from a Serratia marcescens clinical isolate. J Antimicrob Chemother 70:1331–1337. doi:10.1093/jac/dku537.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Ramirez M,
    2. Tolmasky M
    . 2017. Amikacin: uses, resistance, and prospects for inhibition. Molecules 22:2267. doi:10.3390/molecules22122267.
    OpenUrlCrossRef
PreviousNext
Back to top
Download PDF
Citation Tools
Emergence of Klebsiella pneumoniae Harboring the aac(6ʹ)-Ian Amikacin Resistance Gene
Paloma Troyano-Hernáez, Almudena Gutiérrez-Arroyo, Rosa Gómez-Gil, Jesús Mingorance, Fernando Lázaro-Perona
Antimicrobial Agents and Chemotherapy Nov 2018, 62 (12) e01952-18; DOI: 10.1128/AAC.01952-18

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Emergence of Klebsiella pneumoniae Harboring the aac(6ʹ)-Ian Amikacin Resistance Gene
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Emergence of Klebsiella pneumoniae Harboring the aac(6ʹ)-Ian Amikacin Resistance Gene
Paloma Troyano-Hernáez, Almudena Gutiérrez-Arroyo, Rosa Gómez-Gil, Jesús Mingorance, Fernando Lázaro-Perona
Antimicrobial Agents and Chemotherapy Nov 2018, 62 (12) e01952-18; DOI: 10.1128/AAC.01952-18
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • LETTER
    • ACKNOWLEDGMENTS
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Klebsiella pneumoniae
amikacin
aminoglycoside
antibiotic resistance
carbapenemases

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596