Susceptibility testing breakpoints forMycobacterium tuberculosiscategorize isolates with resistance mutations ingyrAas susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB
| Autor: | Jakob Paues, Christian G. Giske, Thomas B. Schön, Katarina Niward, Gunnar Kahlmeter, Kristian Ängeby, Erja Chryssanthou, Judith Bruchfeld, P. Jureen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty Susceptibility testing Tuberculosis 030106 microbiology Antitubercular Agents Mutation Missense Microbial Sensitivity Tests Mycobacterium tuberculosis 03 medical and health sciences Levofloxacin Terminology as Topic Tuberculosis Multidrug-Resistant Genotype medicine Humans Pharmacology (medical) Pharmacology biology business.industry Breakpoint Sequence Analysis DNA biology.organism_classification medicine.disease Virology Surgery Infectious Diseases DNA Gyrase Ofloxacin business Tb treatment Fluoroquinolones medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 71:333-338 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | 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, P 0.05). 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|