Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex

Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patt...

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Main Authors: Nils Wetzstein, Thomas A. Kohl, Sönke Andres, Tilman G. Schultze, Ari Geil, Eunhee Kim, Teodora Biciusca, Christian Hügel, Michael Hogardt, Annette Lehn, Maria J.G.T. Vehreschild, Timo Wolf, Stefan Niemann, Florian P. Maurer, Thomas A. Wichelhaus
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:International Journal of Infectious Diseases
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971220301181
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author Nils Wetzstein
Thomas A. Kohl
Sönke Andres
Tilman G. Schultze
Ari Geil
Eunhee Kim
Teodora Biciusca
Christian Hügel
Michael Hogardt
Annette Lehn
Maria J.G.T. Vehreschild
Timo Wolf
Stefan Niemann
Florian P. Maurer
Thomas A. Wichelhaus
spellingShingle Nils Wetzstein
Thomas A. Kohl
Sönke Andres
Tilman G. Schultze
Ari Geil
Eunhee Kim
Teodora Biciusca
Christian Hügel
Michael Hogardt
Annette Lehn
Maria J.G.T. Vehreschild
Timo Wolf
Stefan Niemann
Florian P. Maurer
Thomas A. Wichelhaus
Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
International Journal of Infectious Diseases
author_facet Nils Wetzstein
Thomas A. Kohl
Sönke Andres
Tilman G. Schultze
Ari Geil
Eunhee Kim
Teodora Biciusca
Christian Hügel
Michael Hogardt
Annette Lehn
Maria J.G.T. Vehreschild
Timo Wolf
Stefan Niemann
Florian P. Maurer
Thomas A. Wichelhaus
author_sort Nils Wetzstein
title Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
title_short Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
title_full Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
title_fullStr Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
title_full_unstemmed Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complex
title_sort comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in mycobacterium avium complex
publisher Elsevier
series International Journal of Infectious Diseases
issn 1201-9712
publishDate 2020-04-01
description Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates. Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients. Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin. Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease. Keywords: NTM, Non-tuberculous mycobacteria, M. avium complex, M. avium, M. chimaera, M. Intracellulare, Drug susceptibility testing, DST
url http://www.sciencedirect.com/science/article/pii/S1201971220301181
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spelling doaj-6b5f11a90f954c65a5582ec8235eaf462020-11-25T03:31:15ZengElsevierInternational Journal of Infectious Diseases1201-97122020-04-0193320328Comparative analysis of phenotypic and genotypic antibiotic susceptibility patterns in Mycobacterium avium complexNils Wetzstein0Thomas A. Kohl1Sönke Andres2Tilman G. Schultze3Ari Geil4Eunhee Kim5Teodora Biciusca6Christian Hügel7Michael Hogardt8Annette Lehn9Maria J.G.T. Vehreschild10Timo Wolf11Stefan Niemann12Florian P. Maurer13Thomas A. Wichelhaus14Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; Corresponding author at: Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.German Center for Infection Research, Research Center Borstel, Borstel, Germany; Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, GermanyNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, GermanyInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Radiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Radiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Pneumology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; German National Consiliary Laboratory on Cystic Fibrosis Bacteriology, GermanyInstitute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, GermanyDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyGerman Center for Infection Research, Research Center Borstel, Borstel, Germany; Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, GermanyNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany; Institute of Medical Microbiology, Virology and Hospital Hygiene, University Medical Center Hamburg- Eppendorf, Hamburg, GermanyInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyObjective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates. Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients. Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin. Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease. Keywords: NTM, Non-tuberculous mycobacteria, M. avium complex, M. avium, M. chimaera, M. Intracellulare, Drug susceptibility testing, DSThttp://www.sciencedirect.com/science/article/pii/S1201971220301181