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J Antimicrob Chemother. 2016 Feb;71(2):333-8. doi: 10.1093/jac/dkv353. Epub 2015 Nov 3.

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.

Author information

1
Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
2
Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden Department of Microbiology, The University of the West Indies, Kingston, Jamaica.
3
Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
4
Unit of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Medicine, Karolinska Institute, Solna, Sweden.
5
The Public Health Agency of Sweden, Stockholm, Sweden.
6
Department of Medical Sciences, Uppsala University, Uppsala, Sweden Department of Clinical Microbiology, Växjö Hospital, Växjö, Sweden.
7
Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden Department of Medical microbiology, Linköping University, Linköping, Sweden tschon@hotmail.com.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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, P < 0.05). The sensitivity and specificity for the MTBDRsl assay compared with gyrA sequencing were 96% and 98%, respectively.

CONCLUSION:

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.

PMID:
26538509
DOI:
10.1093/jac/dkv353
[Indexed for MEDLINE]

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