Molecular characterization of macrolide resistance in Haemophilus influenzae and Haemophilus parainfluenzae strains (2018–21) (2024)

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Irene Cadenas-Jiménez

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

,

Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

,

Madrid

,

Spain

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,

Lucía Saiz-Escobedo

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

,

Spain

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,

Anna Carrera-Salinas

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

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Xenia Camprubí-Márquez

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

,

Spain

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Sara Calvo-Silveria

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

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Madrid

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Spain

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Paula Camps-Massa

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

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Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Respiratory Medicine Department, Hospital Universitari Bellvitge, IDIBELL-UB

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Barcelona

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Spain

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Dàmaris Berbel

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

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Madrid

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Spain

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Fe Tubau

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

,

Madrid

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Spain

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Salud Santos

Research Network for Respiratory Diseases (CIBERES), ISCIII

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Madrid

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Spain

Respiratory Medicine Department, Hospital Universitari Bellvitge, IDIBELL-UB

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Barcelona

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Spain

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M Angeles Domínguez

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

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Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Research Network for Infectious Diseases, CIBERINFEC, ISCIII

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Madrid

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Spain

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Aida González-Díaz

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

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Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

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Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

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Madrid

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Spain

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Carmen Ardanuy

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

,

Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

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Madrid

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Spain

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Sara Martí

Microbiology Department, Hospital Universitari Bellvitge, IDIBELL-UB

,

Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona

,

Spain

Research Network for Respiratory Diseases (CIBERES), ISCIII

,

Madrid

,

Spain

Corresponding author. E-mail: smartinm@bellvitgehospital.cat

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Journal of Antimicrobial Chemotherapy, dkae214, https://doi.org/10.1093/jac/dkae214

Published:

01 July 2024

Article history

Received:

15 March 2024

Accepted:

07 June 2024

Published:

01 July 2024

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    Irene Cadenas-Jiménez, Lucía Saiz-Escobedo, Anna Carrera-Salinas, Xenia Camprubí-Márquez, Sara Calvo-Silveria, Paula Camps-Massa, Dàmaris Berbel, Fe Tubau, Salud Santos, M Angeles Domínguez, Aida González-Díaz, Carmen Ardanuy, Sara Martí, Molecular characterization of macrolide resistance in Haemophilus influenzae and Haemophilus parainfluenzae strains (2018–21), Journal of Antimicrobial Chemotherapy, 2024;, dkae214, https://doi.org/10.1093/jac/dkae214

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Abstract

Objectives

This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (n = 2556) and Haemophilus parainfluenzae (n = 510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain.

Methods

Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures.

Results

Macrolide resistance was detected in 67 H. influenzae (2.6%) and 52 (10.2%) H. parainfluenzae strains and associated with resistance to other antimicrobials (co-trimoxazole, chloramphenicol, tetracycline). Differences in macrolide resistance existed between the two species. Acquired resistance genes were more prevalent in H. parainfluenzae (35/52; 67.3%) than in H. influenzae (12/67; 17.9%). Gene mutations and amino acid substitutions were more common in H. influenzae (57/67; 85%) than in H. parainfluenzae (16/52; 30.8%). Substitutions in L22 and in 23S rRNA were only detected in H. influenzae (34.3% and 29.0%, respectively), while substitutions in L4 and AcrAB/AcrR were observed in both species. The MEGA element was identified in 35 (67.3%) H. parainfluenzae strains, five located in an integrative and conjugative element (ICE); by contrast, 11 (16.4%) H. influenzae strains contained the MEGA element (all in an ICE). A new ICEHpaHUB8 was described in H. parainfluenzae.

Conclusions

Macrolide resistance was higher in H. parainfluenzae than in H. influenzae, with differences in the underlying mechanisms. H. parainfluenzae exhibits co-resistance to other antimicrobials, often leading to an extensively drug-resistant phenotype. This highlights the importance of conducting antimicrobial resistance surveillance.

© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

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