Interim outcomes of delamanid for the treatment of MDR- and XDR-TB in South Korea.

Objectives: Delamanid is a new anti-TB drug, but few data exist on its use outside clinical trials. The purpose of this study was to evaluate the efficacy as well as the safety and tolerability of a delamanid-containing regimen for 24 weeks in the treatment of MDR- and XDR-TB. Methods: We performed a retrospective cohort study among patients with MDR/XDR-TB who were treated with a delamanid-containing regimen in seven hospitals in South Korea. Results: A total of 32 patients with MDR-TB, of which 6 (18.8%) were XDR-TB, were included and all completed 24 weeks of delamanid treatment. Of 19 patients (59.4%) who had positive culture sputum at the initiation of delamanid treatment, the proportion of culture conversion at 8 weeks was 72.2% (13 of 18) in solid medium and 50.0% (7 of 14) in liquid medium. The proportion of culture conversion at 24 weeks was 94.4% (17 of 18) in solid medium and 92.9% (13 of 14) in liquid medium. The median time to culture conversion was 33 days (range = 5-81) using solid medium and 57 days (range = 8-96) using liquid medium. Of the 32 patients, there was no serious adverse event or death. Three patients developed a transient QTcF of > 500 ms. Conclusions: The use of delamanid combined with optimized background regimens has the potential to achieve high culture conversion rates at 24 weeks with an acceptable safety and tolerability profile in patients with MDR/XDR-TB.

Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with non-small cell lung cancer.

BACKGROUND: Somatic mutations of the gene encoding epidermal growth factor receptor (EGFR) are detected in approximately 30%-50% of patients with non-small cell lung cancers (NSCLC), so detection of EGFR mutation is the pivotal step of treatment in patients with advanced NSCLC. However, difficulty in obtaining sufficient tissue and bias from the heterogeneity of the tumor samples are the major obstacles. Although analyzing EGFR with circulating tumor DNA (ctDNA) in plasma is a breakthrough, accuracy is the problem in variable methods. Peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis (PANAMutyper®) is a novel and highly sensitive method of detecting EGFR mutation in tumor tissues. AIMS AND OBJECTIVES: This study was designed to evaluate PANAMutyper® for detecting EGFR mutation with ctDNA of patients with lung cancer. MATERIALS AND METHODS: EGFR mutation status detected by PNA clamp with tissue samples and by PANAMutyper® with ctDNA was compared. Tissue biopsy was done in 158 patients with lung tumor, in which 23 cases were excluded and 135 cases were enrolled. EGFR mutation rate was 23.0% (31/135) in overall patients. All the plasma samples of the cases with mutant EGFR in tissue samples were verified by an already known highly sensitive method of droplet digital polymerase chain reaction (ddPCR). RESULTS: The concordance rate of tissue and plasma samples was 91.9% (124/135). The sensitivity, specificity, negative predictive value, and positive predictive value were 64.5%, 100%, 90.4%, and 100%, respectively, according to the tissue samples as a standard. PANAMutyper® method was not inferior to ddPCR for the detection of EGFR mutation including T790M with ctDNA. These results suggest that the detection of EGFR mutation status using ctDNA in plasma by PANAMutyper® is a feasible test prior to tissue biopsy.

Trend of multidrug and fluoroquinolone resistance in Mycobacterium tuberculosis isolates from 2010 to 2014 in Korea: a multicenter study.

BACKGROUND/AIMS: This study was conducted to evaluate the recent prevalence and trend of anti-tuberculosis (TB) drug resistance with a focus on multidrug-resistance (MDR) and fluoroquinolone resistance in South Korea. METHODS: We retrospectively reviewed the drug susceptibility testing results of culture-confirmed Mycobacterium tuberculosis isolates collected from 2010 to 2014 at seven tertiary hospitals in South Korea. RESULTS: A total of 5,599 cases were included: 4,927 (88.0%) were new cases and 672 (12.0%) were previously treated cases. The MDR rate has significantly decreased from 6.0% in 2010 to 3.0% in 2014 among new cases, and from 28.6% in 2010 to 18.4% in 2014 among previously treated cases (p < 0.001 and p = 0.027, respectively). The resistance rate to any f luoroquinolone was 0.8% (43/5,221) in non-MDR-TB patients, as compared to 26.2% (99/378) in MDR-TB patients (p < 0.001). There was no significant change in the trend of fluoroquinolone resistance among both nonMDR-TB and MDR-TB patients. Among the 43 non-MDR-TB patients with fluoroquinolone resistance, 38 (88.4%) had fluoroquinolone mono-resistant isolates. CONCLUSION: The prevalence of MDR-TB has significantly decreased from 2010 to 2014. The prevalence of fluoroquinolone resistance among non-MDR-TB patients was low, but the existence of fluoroquinolone mono-resistant TB may be a warning on the widespread use of fluoroquinolone in the community.