Abstract
BackgroundFluoroquinolones are broad-spectrum antibiotics that are recommended, and increasingly important, for the treatment of multidrug-resistant tuberculosis (MDR-TB). Resistance to fluoroquinolones is caused by mutations in the Quinolone Resistance Determining Region (QRDR) of gyrA and gyrB genes of Mycobacterium tuberculosis. In this study, we characterized the phenotypic and genotypic resistance to fluoroquinolones for the first time in northeast Iran.MethodsA total of 123 Mycobacterium tuberculosis isolates, including 111 clinical and 12 collected multidrug-resistant isolates were studied. Also, 19 WHO quality control strains were included in the study. The phenotypic susceptibility was determined by the proportion method on Löwenstein-Jensen medium. The molecular cause of resistance to the fluoroquinolone drugs ofloxacin and levofloxacin was investigated by sequencing of the QRDR region of the gyrA and gyrB genes.ResultsAmong 123 isolates, six (4.8%) were fluoroquinolone-resistant according to phenotypic methods, and genotypically three of them had a mutation at codon 94 of the gyrA gene (Asp→ Gly) which was earlier reported to cause resistance. All three remaining phenotypically resistant isolates had a nucleotide change in codon 95. No mutations were found in the gyrB gene. Five of the 19 WHO quality control strains, were phenotypically fluoroquinolone-resistant, four of them were genotypically resistant with mutations at codon 90, 91 of the gyrA gene and one resistant strain had no detected mutation.ConclusionsMutation at codon 94 of the gyrA gene, was the main cause of fluoroquinolone resistance among M. tuberculosis isolates in our region. In 3/6 fluoroquinolone-resistant isolates, no mutations were found in either gyrA or gyrB. Therefore, it can be concluded that various other factors may lead to fluoroquinolone resistance, such as active efflux pumps, decreased cell wall permeability, and drug inactivation.
Highlights
Fluoroquinolones are broad-spectrum antibiotics that are recommended, and increasingly important, for the treatment of multidrug-resistant tuberculosis (MDR-TB)
Note: Pansusceptible: susceptible to all first-line anti-TB drugs, FQ mono resistance: being resistant only to FQ, but sensitive to all first-line TB drugs, MDR-TB: resistance to at least both isoniazid and rifampin, Polydrug resistance: resistance to more than one first-line anti-TB drug, other than both isoniazid and rifampin aThese three isolates were all related to Iranian patients
A second-line anti-TB drug and a third-line drug were evaluated for the analysis of phenotypic Drug susceptibility test (DST) and genotypic resistance to FQs. They were examined on 111 clinical isolates of M. tuberculosis, 12 MDR-TB isolates, and 19 WHO quality control strains sent to the laboratory
Summary
Fluoroquinolones are broad-spectrum antibiotics that are recommended, and increasingly important, for the treatment of multidrug-resistant tuberculosis (MDR-TB). MDR-TB is defined as Mycobacterium tuberculosis strains that are resistant to the main first-line drugs (isoniazid and rifampin) [7]. XDR-TB strains are characterized by resistance to at least one of the three injectable aminoglycosides (kanamycin, amikacin, capreomycin) and fluoroquinolones (FQs), as well as isoniazid and rifampin [8]. The development of such resistant strains is a serious threat to the global control of tuberculosis [9,10,11]
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