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Susceptibility

Reevaluation of the Critical Concentration for Drug Susceptibility Testing of Mycobacterium tuberculosis against Pyrazinamide Using Wild-Type MIC Distributions and pncA Gene Sequencing

J. Werngren, E. Sturegård, P. Juréen, K. Ängeby, S. Hoffner, T. Schön
J. Werngren
aDepartment of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden
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E. Sturegård
bMedical Microbiology, Department of Laboratory Medicine, Lund University, Malmö, Sweden
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P. Juréen
aDepartment of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden
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K. Ängeby
cClinical Microbiology, MTC-Karolinska Institutet, Karolinska University Hospital, Stockholm Sweden
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S. Hoffner
aDepartment of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden
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T. Schön
dDepartment of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden
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DOI: 10.1128/AAC.05894-11
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    Fig 1

    MIC distribution of PZA determined by Bactec MGIT 960 for 46 M. tuberculosis strains compared to the presence or absence of pncA mutations (mut) and to previously obtained Bactec 460 (B460) susceptibility results. IRES stands for isoniazid, rifampin, ethambutol, streptomycin. One isolate with an MIC of 32 mg/liter had a silent pncA mutation.

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    Pyrazinamide MICs in Bactec MGIT 960 system correlated to pncA gene sequencing data and previously obtained Bactec 460 results for 46 M. tuberculosis strains

    Strain groupMGIT PZA MIC (mg/liter)No. of strainspncA amino acid changePrevious BACTEC 460 resultc
    PZAINHRIFEMBSM
    Consecutive fully susceptible strains≤81NoneSSSSS
    164NoneSSSSS
    328NoneSSSSS
    642NoneSSSSS
    Nonconsecutive strains with MICs less than or equal to ECOFF (≤64 mg/liter)161NoneSSSSS
    322NoneSSSSS
    321NoneSSRSS
    321aSer65SerSRRSS
    643NoneSSSSS
    641NoneRRSSR
    641NoneSRSSS
    641aThr47AlaRRRRR
    Nonconsecutive strains with MICs greater than ECOFF (>64 mg/liter)1281aNoneSSSSS
    1281bPhe58LeuRRRSS
    2561aNoneRRRRR
    2561Ser65Ser/frameshiftRRRSS
    2561Ile6ThrRRRRS
    2561Val125PheRRRSS
    5121Pro54LeuRRRSS
    5121Phe58LeuRRRSR
    1,0241Gly132AlaRRRRR
    1,0241Leu172ProRRRRS
    1,0241Val155GlyRRRSR
    >1,0241Val155GlyRRRSS
    >1,0241Met175ThrRRRRR
    >1,0241Pro54SerRRRRS
    >1,0241Gly132SerRRRRS
    >1,0241FrameshiftRRRSR
    >1,0241bHis51GlnRSSSS
    >1,0241Arg123ProRSSSS
    >1,02414-amino-acid in-frame insertionRRRSS
    >1,0241Thr142LysRRRRS
    • ↵a PZase positive.

    • ↵b PZase negative.

    • ↵c INH, isoniazid (0.1 mg/liter); RIF, rifampin (1 mg/liter); EMB, ethambutol (2.5 mg/liter); SM, streptomycin (1 mg/liter); PZA, pyrazinamide (100 mg/liter); R, resistant; S, susceptible.

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Reevaluation of the Critical Concentration for Drug Susceptibility Testing of Mycobacterium tuberculosis against Pyrazinamide Using Wild-Type MIC Distributions and pncA Gene Sequencing
J. Werngren, E. Sturegård, P. Juréen, K. Ängeby, S. Hoffner, T. Schön
Antimicrobial Agents and Chemotherapy Feb 2012, 56 (3) 1253-1257; DOI: 10.1128/AAC.05894-11

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Reevaluation of the Critical Concentration for Drug Susceptibility Testing of Mycobacterium tuberculosis against Pyrazinamide Using Wild-Type MIC Distributions and pncA Gene Sequencing
J. Werngren, E. Sturegård, P. Juréen, K. Ängeby, S. Hoffner, T. Schön
Antimicrobial Agents and Chemotherapy Feb 2012, 56 (3) 1253-1257; DOI: 10.1128/AAC.05894-11
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