Isoniazid Resistance in Mycobacterium tuberculosis Is a Heterogeneous Phenotype Composed of Overlapping MIC Distributions with Different Underlying Resistance Mechanisms

Author:

Ghodousi Arash1ORCID,Tagliani Elisa1,Karunaratne Eranga2,Niemann Stefan34,Perera Jennifer2,Köser Claudio U.5ORCID,Cirillo Daniela Maria1ORCID

Affiliation:

1. Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

2. Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

3. Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany

4. German Center for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Germany

5. Department of Genetics, University of Cambridge, Cambridge, United Kingdom

Abstract

MIC testing using the Bactec mycobacteria growth indicator tube system 960 of 70 phylogenetically diverse, isoniazid-resistant clinical strains of Mycobacterium tuberculosis revealed a complex pattern of overlapping MIC distributions. Whole-genome sequencing explained most of the levels of resistance observed.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference23 articles.

1. Clinical and Laboratory Standards Institute. 2018. Susceptibility testing of susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes—3rd ed. CLSI standard M24. Clinical and Laboratory Standards Institute, Wayne, PA.

2. Clinical and Laboratory Standards Institute. 2018. Performance standards for susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes—1st ed. CLSI supplement M62. Clinical and Laboratory Standards Institute, Wayne, PA.

3. ‘Those who cannot remember the past are condemned to repeat it’: Drug-susceptibility testing for bedaquiline and delamanid

4. NCCLS. 2003. Susceptibility testing of mycobacteria, Nocardiae, and other aerobic actinomycetes; approved standard. NCCLS document M24-A. NCCLS, Wayne, PA.

5. World Health Organization. 2018. Technical manual for drug susceptibility testing of medicines used in the treatment of tuberculosis [WHO/CDS/TB/2018.24]. World Health Organization, Geneva, Switzerland. http://www.who.int/tb/publications/2018/WHO_technical_drug_susceptibility_testing/en/. Accessed 17 November 2018.

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