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Mycobacteriology and Aerobic Actinomycetes

Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus

Nils Wetzstein, Thomas A. Kohl, Tilman G. Schultze, Sönke Andres, Carla Bellinghausen, Christian Hügel, Volkhard A. J. Kempf, Annette Lehn, Michael Hogardt, Hubert Serve, Maria J. G. T. Vehreschild, Timo Wolf, Stefan Niemann, Florian P. Maurer, Thomas A. Wichelhaus
Christine Y. Turenne, Editor
Nils Wetzstein
aDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Thomas A. Kohl
cGerman Center for Infection Research, Research Center Borstel, Borstel, Germany
dMolecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany
eNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany
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Tilman G. Schultze
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
fInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
gUniversity Center of Competence of Infection Control of the State of Hesse, Frankfurt am Main, Germany
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Sönke Andres
eNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany
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Carla Bellinghausen
hDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Christian Hügel
hDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Volkhard A. J. Kempf
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
fInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
gUniversity Center of Competence of Infection Control of the State of Hesse, Frankfurt am Main, Germany
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Annette Lehn
iInstitute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Germany
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Michael Hogardt
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
fInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
gUniversity Center of Competence of Infection Control of the State of Hesse, Frankfurt am Main, Germany
jNational Consiliary Laboratory on Cystic Fibrosis Bacteriology, Frankfurt am Main, Germany
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Hubert Serve
kDepartment of Internal Medicine, Hematology and Oncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Maria J. G. T. Vehreschild
aDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Timo Wolf
aDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
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Stefan Niemann
cGerman Center for Infection Research, Research Center Borstel, Borstel, Germany
dMolecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany
eNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany
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Florian P. Maurer
eNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany
lInstitute of Medical Microbiology, Virology and Hospital Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Thomas A. Wichelhaus
bUniversity Center of Infectious Diseases, UCI, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
fInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
gUniversity Center of Competence of Infection Control of the State of Hesse, Frankfurt am Main, Germany
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Christine Y. Turenne
St. Boniface Hospital
Roles: Editor
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DOI: 10.1128/JCM.01813-20
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ABSTRACT

Mycobacterium abscessus is a highly antibiotic-resistant opportunistic pathogen causing clinically challenging infections in patients with preexisting lung diseases or under immunosuppression. Hence, reliable antibiotic susceptibility data are required for effective treatment. Aims of this study were to investigate (i) the congruence of genotypic and phenotypic antimicrobial susceptibility testing, (ii) the relationship between resistance profile and clinical course, and (iii) the phylogenetic relations of M. abscessus in a German patient cohort. A total of 39 isolates from 29 patients infected or colonized with M. abscessus underwent genotypic and phenotypic drug susceptibility testing. Clinical data were correlated with susceptibility data. Phylogenetic analysis was performed by means of whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analysis. Macrolide resistance was mainly mediated by functional Erm(41) methyltransferases (T28 sequevars) in M. abscessus subsp. abscessus (n = 25) and M. abscessus subsp. bolletii (n = 2). It was significantly associated with impaired culture conversion (P = 0.02). According to the core SNP phylogeny, we identified three clusters of closely related isolates with SNP distances below 25. Representatives of all circulating global clones (Absc. 1, Absc. 2, and Mass. 1) were identified in our cohort. However, we could not determine evidence for in-hospital interhuman transmission from clinical data. In our patient cohort, we identified three M. abscessus clusters with closely related isolates and representatives of the previously described international clusters but no human-to-human in-hospital transmission. Macrolide and aminoglycoside susceptibility data are critical for therapeutic decision-making in M. abscessus infections.

FOOTNOTES

    • Received 13 July 2020.
    • Returned for modification 14 August 2020.
    • Accepted 8 September 2020.
    • Accepted manuscript posted online 16 September 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus
Nils Wetzstein, Thomas A. Kohl, Tilman G. Schultze, Sönke Andres, Carla Bellinghausen, Christian Hügel, Volkhard A. J. Kempf, Annette Lehn, Michael Hogardt, Hubert Serve, Maria J. G. T. Vehreschild, Timo Wolf, Stefan Niemann, Florian P. Maurer, Thomas A. Wichelhaus
Journal of Clinical Microbiology Nov 2020, 58 (12) e01813-20; DOI: 10.1128/JCM.01813-20

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Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus
Nils Wetzstein, Thomas A. Kohl, Tilman G. Schultze, Sönke Andres, Carla Bellinghausen, Christian Hügel, Volkhard A. J. Kempf, Annette Lehn, Michael Hogardt, Hubert Serve, Maria J. G. T. Vehreschild, Timo Wolf, Stefan Niemann, Florian P. Maurer, Thomas A. Wichelhaus
Journal of Clinical Microbiology Nov 2020, 58 (12) e01813-20; DOI: 10.1128/JCM.01813-20
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KEYWORDS

Mycobacterium abscessus
NTM
antibiotic susceptibility
nontuberculous mycobacteria
transmission

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