pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea

BACKGROUND: Pyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide. RESULTS: Of the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns. CONCLUSION: These data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes

Acute Cerebral Phaeohyphomycosis due to Wangiella dermatitidis Accompanied by Cerebrospinal Fluid Eosinophilia

We report a case of cerebral phaeohyphomycosis due to Wangiella dermaitidis in an immunocompetent adult man. His cerebrospinal fluid (CSF) showed pleocytosis with a high eosinophil count but without peripheral blood eosinophilia. The present case suggested that this black yeast-like fungus should be included when the causes of CSF eosinophilia are considered, even though it is an extremely rare pathogen

Evaluation of a Colorimetric Antifungal Susceptibility Test by Using 2,3-Diphenyl-5-Thienyl-(2)-Tetrazolium Chloride

A colorimetric antifungal susceptibility test was performed using 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride. Among 24 strains of Candida species, no trailing growth was found. In 22 and 20 strains, the MICs obtained in the colorimetric assay were within two dilutions of those obtained by the National Committee for Clinical Laboratory Standards method for ketoconazole and itraconazole, respectively

Reduction of Contamination of Mycobacterial Growth Indicator Tubes with a Modified Antimicrobial Combination

Culture in the fluorimetric Mycobacteria Growth Indicator Tube (MGIT) treated with a combination of vancomycin, amphotericin B, and nalidixic acid (VAN) showed growth of most strains of 31 mycobacterial species with a less-than-1-day delay. The results were similar to those in the MGIT with polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin, but with respiratory specimens, the MGIT with VAN showed a lower contamination rate with no change in the detection rate or time

Incidence and Prognostic Impact of DNMT3A Mutations in Korean Normal Karyotype Acute Myeloid Leukemia Patients

Background. DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients. Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status. Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P = 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly. Conclusions. Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients