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

doi:10.1128/AAC.05894-11

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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Table 1

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 group	MGIT PZA MIC (mg/liter)	No. of strains	pncA amino acid change	Previous BACTEC 460 result^c
Strain group	MGIT PZA MIC (mg/liter)	No. of strains	pncA amino acid change	PZA	INH	RIF	EMB	SM
Consecutive fully susceptible strains	≤8	1	None	S	S	S	S	S
	16	4	None	S	S	S	S	S
	32	8	None	S	S	S	S	S
	64	2	None	S	S	S	S	S
Nonconsecutive strains with MICs less than or equal to ECOFF (≤64 mg/liter)	16	1	None	S	S	S	S	S
	32	2	None	S	S	S	S	S
	32	1	None	S	S	R	S	S
	32	1^a	Ser65Ser	S	R	R	S	S
	64	3	None	S	S	S	S	S
	64	1	None	R	R	S	S	R
	64	1	None	S	R	S	S	S
	64	1^a	Thr47Ala	R	R	R	R	R
Nonconsecutive strains with MICs greater than ECOFF (>64 mg/liter)	128	1^a	None	S	S	S	S	S
	128	1^b	Phe58Leu	R	R	R	S	S
	256	1^a	None	R	R	R	R	R
	256	1	Ser65Ser/frameshift	R	R	R	S	S
	256	1	Ile6Thr	R	R	R	R	S
	256	1	Val125Phe	R	R	R	S	S
	512	1	Pro54Leu	R	R	R	S	S
	512	1	Phe58Leu	R	R	R	S	R
	1,024	1	Gly132Ala	R	R	R	R	R
	1,024	1	Leu172Pro	R	R	R	R	S
	1,024	1	Val155Gly	R	R	R	S	R
	>1,024	1	Val155Gly	R	R	R	S	S
	>1,024	1	Met175Thr	R	R	R	R	R
	>1,024	1	Pro54Ser	R	R	R	R	S
	>1,024	1	Gly132Ser	R	R	R	R	S
	>1,024	1	Frameshift	R	R	R	S	R
	>1,024	1^b	His51Gln	R	S	S	S	S
	>1,024	1	Arg123Pro	R	S	S	S	S
	>1,024	1	4-amino-acid in-frame insertion	R	R	R	S	S
	>1,024	1	Thr142Lys	R	R	R	R	S

↵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.