Genotypic and phenotypic characterization of Mycobacterium tuberculosis resistance against fluoroquinolones in the northeast of Iran.

BACKGROUND: Fluoroquinolones 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: Mutation 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.

The association of Epstein-Barr virus infection with multiple myeloma.

BACKGROUND: Multiple myeloma is a conventional term for clonal proliferation of plasma cells. It is suggested that viruses may have a significant role in the pathogenesis of multiple myeloma. AIMS: The aim of this study was to evaluate whether there is an association between multiple myeloma and Epstein-Barr Virus (EBV) by the polymerase chain reaction (PCR) method. MATERIALS AND METHODS: This case-control study was performed on 60 paraffin-embedded bone marrow biopsies (30 multiple myeloma and 30 normal bone marrow specimens) in the molecular pathology section of our hospital. The patients and control groups were matched according to gender and age. Several sections were cut from each paraffin blocks, and then the deoxyribonucleic acid (DNA) was extracted by the non-heating extraction method. In the next step, PCR was carried out for detection of EBV genome and finally its products were analyzed by electrophoresis. RESULTS: DNA of EBV was detected in 10 patients of the case group (5 males and 5 females) and 3 subjects (2 males and 1 female) of the control group. The Pearson chi-square test showed significant difference between case and control group (P=0.03) for detection of the EBV genome. In myeloma patients, the mean white blood cell count was 9.05 + 4.02 and 5.20 + 2.02 Χ 10(9) /L in EBV positive and negative groups, respectively and a significant difference count was seen for the WBC count. RECOMMENDATIONS: Our results show an association between multiple myeloma and EBV infection.