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Susceptibility testing breakpoints for Mycobacterium tuberculosis categorize isolates with resistance mutations in gyrA as susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB
Linkoping Univ Hosp, Dept Infect Dis, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.;Univ W Indies, Dept Microbiol, Kingston 7, Jamaica..
Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden..
Linkoping Univ Hosp, Dept Infect Dis, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
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2016 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 2, 333-338 p.Article in journal (Refereed) PublishedText
Abstract [en]

Fluoroquinolones (FQs) are important in the treatment of MDR-TB and in the definition of XDR-TB. Our objective was to investigate how discrepancies in the phenotypic and genotypic methods for antimicrobial susceptibility testing could affect the interpretation of antimicrobial susceptibility test results. We analysed MICs of ofloxacin and levofloxacin in Middlebrook 7H10 broth (7H10) as well as sequencing of the quinolone resistance-determining region of the gyrA gene and the MTBDRsl assay in 75 resistant isolates, including MDR and XDR strains of Mycobacterium tuberculosis. Among 75 resistant isolates, 27 had mutations associated with FQ resistance. Among isolates with resistance mutations in gyrA, 26% (seven of 27) were susceptible to levofloxacin and ofloxacin by phenotypic testing at 1 mg/L and 2 mg/L. The most common mutation was in codon 94 and these isolates had significantly increased MICs of levofloxacin (2-8 mg/L) compared with isolates with mutations in codon 90 (0.25-2 mg/L, PaEuroS < aEuroS0.05). The sensitivity and specificity for the MTBDRsl assay compared with gyrA sequencing were 96% and 98%, respectively. Current critical concentrations may classify up to 26% of isolates with gyrA mutations as susceptible to FQs due to a close relationship between susceptible and resistant populations. These results should be considered while improving clinical breakpoints for M. tuberculosis and may have an impact on the definition of XDR-TB.

Place, publisher, year, edition, pages
2016. Vol. 71, no 2, 333-338 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-288631DOI: 10.1093/jac/dkv353ISI: 000372427600008PubMedID: 26538509OAI: oai:DiVA.org:uu-288631DiVA: diva2:926233
Funder
Swedish Heart Lung FoundationSwedish Society of MedicineMarianne and Marcus Wallenberg Foundation
Available from: 2016-05-04 Created: 2016-04-28 Last updated: 2016-05-04Bibliographically approved

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