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Clinical Therapeutics

A Multimethod, Multicountry Evaluation of Breakpoints for Bedaquiline Resistance Determination

Nazir Ahmed Ismail, Akio Aono, Emanuele Borroni, Daniela Maria Cirillo, Christel Desmaretz, Rumina Hasan, Satoshi Mitarai, Sadia Shakoor, Gabriela Torrea, Koné Kaniga, Shaheed V. Omar
Nazir Ahmed Ismail
aCenter for Tuberculosis and WHO Supranational TB Reference Laboratory, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa
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Akio Aono
bDepartment of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-tuberculosis Association, Kiyose, Japan
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Emanuele Borroni
cEmerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy
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Daniela Maria Cirillo
cEmerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy
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Christel Desmaretz
dDepartment of Biomedical Sciences, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
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Rumina Hasan
eDepartment of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan
fFaculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, United Kingdom
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Satoshi Mitarai
bDepartment of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan Anti-tuberculosis Association, Kiyose, Japan
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Sadia Shakoor
eDepartment of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan
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Gabriela Torrea
dDepartment of Biomedical Sciences, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
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Koné Kaniga
gJohnson & Johnson Global Public Health, Titusville, New Jersey, USA
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Shaheed V. Omar
aCenter for Tuberculosis and WHO Supranational TB Reference Laboratory, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa
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DOI: 10.1128/AAC.00479-20
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    FIG 1

    BDQ MIC distribution for BMD frozen plates by particular laboratory (a) and by all laboratories (n = 494) (b). The total number of isolates was 494 (Lab 1, 104; Lab 2, 100; Lab 3, 100; Lab 4, 91; and Lab 5, 99). The arrow indicates the ECOFF determined by visual inspection.

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    FIG 2

    BDQ MIC distribution for BMD dry plates by particular laboratory (a) and by all laboratories (n = 494) (b). The total number of isolates was 494 (Lab 1, 104; Lab 2, 100; Lab 3, 100; Lab 4, 91; and Lab 5, 99). The arrow indicates the ECOFF determined by visual inspection.

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    FIG 3

    ECOFF plots and values for BMD frozen (a) and dry (b) plates.

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    FIG 4

    Diagrammatic representation of BDQ DST results for discordance isolates by method stratified by CRS susceptible (n = 14) (a) and resistant (n = 10) (b). AP, agar proportion; BMD, broth microdilution.

Tables

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  • TABLE 1

    Rv0678 variants and number of DST methods classifying resistance (n = 28)a

    TABLE 1
    • ↵a RAV, resistance-associated variant; WT, wild-type (includes the –11C>A mutation in one isolate).

  • TABLE 2

    Prevalence of BDQ resistance by method and composite reference standarda

    TABLE 2
    • ↵a CC, critical concentration; BP, MIC breakpoint; NA, not applicable; CRS, composite reference standard. The CC is indicated for the agar proportion (AP) and MGIT960 methods; the BP is indicated for BMD frozen and BMD dry methods.

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A Multimethod, Multicountry Evaluation of Breakpoints for Bedaquiline Resistance Determination
Nazir Ahmed Ismail, Akio Aono, Emanuele Borroni, Daniela Maria Cirillo, Christel Desmaretz, Rumina Hasan, Satoshi Mitarai, Sadia Shakoor, Gabriela Torrea, Koné Kaniga, Shaheed V. Omar
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00479-20; DOI: 10.1128/AAC.00479-20

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A Multimethod, Multicountry Evaluation of Breakpoints for Bedaquiline Resistance Determination
Nazir Ahmed Ismail, Akio Aono, Emanuele Borroni, Daniela Maria Cirillo, Christel Desmaretz, Rumina Hasan, Satoshi Mitarai, Sadia Shakoor, Gabriela Torrea, Koné Kaniga, Shaheed V. Omar
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00479-20; DOI: 10.1128/AAC.00479-20
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KEYWORDS

Mycobacterium tuberculosis
bedaquiline
drug resistance
drug susceptibility testing
tuberculosis

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