Pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis isolates in Japan

Ando, Hiromitsu; Mitarai, Satoshi; Kondo, Yuji; Suetake, Toshinori; Sekiguchi, Jun‐ichiro; Kato, Seiya; Mori, Toru; Kirikae, Teruo

doi:10.1111/j.1469-0691.2009.03078.x

Cited by 44 publications

(34 citation statements)

References 11 publications

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“…It is also important to detect resistance to PZA and LVX in MDR tuberculosis, as the majority of MDR M. tuberculosis isolates have been reported to be resistant to either PZA or LVX in Japan (4,5).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Multicenter Evaluation of a New Line Probe Assay Kit for Identification of Mycobacterium Species and Detection of Drug-Resistant Mycobacterium tuberculosis

et al. 2012

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We evaluated a new line probe assay (LiPA) kit to identify Mycobacterium species and to detect mutations related to drug resistance in Mycobacterium tuberculosis. A total of 554 clinical isolates of Mycobacterium tuberculosis (n ‫؍‬ 316), Mycobacterium avium (n ‫؍‬ 71), Mycobacterium intracellulare (n ‫؍‬ 51), Mycobacterium kansasii (n ‫؍‬ 54), and other Mycobacterium species (n ‫؍‬ 62) were tested with the LiPA kit in six hospitals. The LiPA kit was also used to directly test 163 sputum specimens. The results of LiPA identification of Mycobacterium species in clinical isolates were almost identical to those of conventional methods. Compared with standard drug susceptibility testing results for the clinical isolates, LiPA showed a sensitivity and specificity of 98.9% and 97.3%, respectively, for detecting rifampin (RIF)-resistant clinical isolates; 90.6% and 100%, respectively, for isoniazid (INH) resistance; 89.7% and 96.0%, respectively, for pyrazinamide (PZA) resistance; and 93.0% and 100%, respectively, for levofloxacin (LVX) resistance. The LiPA kit could detect target species directly in sputum specimens, with a sensitivity of 85.6%. Its sensitivity and specificity for detecting RIF-, PZA-, and LVX-resistant isolates in the sputum specimens were both 100%, and those for detecting INH-resistant isolates were 75.0% and 92.9%, respectively. The kit was able to identify mycobacterial bacilli at the species level, as well as drug-resistant phenotypes, with a high sensitivity and specificity.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Multicenter Evaluation of a New Line Probe Assay Kit for Identification of Mycobacterium Species and Detection of Drug-Resistant Mycobacterium tuberculosis

et al. 2012

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“…Other studies also report synonymous or neutral mutations in PZA s isolates (2,9,14,17,23,55,58). We identified 5 possible pncA alterations not associated with a drug resistance phenotype among 138 sequenced clinical isolates, even though the considered mutation or codon has been described in the literature as being associated with PZA r : 14 Cys ¡ Gly (56), 64 Tyr ¡ Ser (29,42), 135 Thr ¡ Pro (17,40,56), 143 Ala ¡ Thr (17), and 175 Met ¡ Ile (29,31,53).…”

Section: Pyrazinamide-resistant Mycobacterium Tuberculosismentioning

confidence: 99%

Systematic Analysis of Pyrazinamide-Resistant Spontaneous Mutants and Clinical Isolates of Mycobacterium tuberculosis

Stoffels

Mathys

Fauville-Dufaux

et al. 2012

Antimicrob Agents Chemother

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b Pyrazinamide (PZA) is a first-line antitubercular drug known for its activity against persistent Mycobacterium tuberculosis bacilli. We set out to systematically determine the PZA susceptibility profiles and mutations in the pyrazinamidase (pncA) gene of a collection of multidrug-resistant tuberculosis (MDR-TB) clinical isolates and PZA-resistant (PZA r ) spontaneous mutants. The frequency of acquired resistance to PZA was determined to be 10 ؊5 bacilli in vitro. Selection at a lower concentration of PZA yielded a significantly larger number of spontaneous mutants. The methodical approach employed allowed for determination of the frequency of the PZA r phenotype correlated with mutations in the pncA gene, which was 87.5% for the laboratory-selected spontaneous mutants examined in this study. As elucidated by structural analysis, most of the identified mutations were foreseen to affect protein activity through either alteration of an active site residue or destabilization of protein structure, indicating some preferential mutation site rather than random scattering. Twelve percent of the PZA r mutants did not have a pncA mutation, strongly indicating the presence of at least one other mechanism(s) of PZA r .

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“…2 Since testing is not routinely performed, the prevalence of PZA resistance is not well known; however, surveillance studies have reported prevalence of 52%-78% in treatment failure or MDR-TB cases, and 2%-10% in non-MDR-TB cases. 1,7,9,10 PZA is a pro-drug that enters bacteria by passive diffusion and is converted to its active form, pyrazinoic acid (POA), by bacterial pyrazinamidase (PZAse). 6,12,19 POA is expelled from the mycobacterium by an efflux pump, it is protonated in the acidic extracellular space, and the protonated form is then reabsorbed into the bacilli, where the proton is released.…”

Section: Introductionmentioning

confidence: 99%

A New Approach for Pyrazinamide Susceptibility Testing inMycobacterium tuberculosis

Zimic

Loli

Gilman

et al. 2012

Microbial Drug Resistance

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Pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis isolates in Japan

Cited by 44 publications

References 11 publications

Comprehensive Multicenter Evaluation of a New Line Probe Assay Kit for Identification of Mycobacterium Species and Detection of Drug-Resistant Mycobacterium tuberculosis

Comprehensive Multicenter Evaluation of a New Line Probe Assay Kit for Identification of Mycobacterium Species and Detection of Drug-Resistant Mycobacterium tuberculosis

Systematic Analysis of Pyrazinamide-Resistant Spontaneous Mutants and Clinical Isolates of Mycobacterium tuberculosis

A New Approach for Pyrazinamide Susceptibility Testing inMycobacterium tuberculosis

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