Current Status of Fluoroquinolone Use for Treatment of Tuberculosis in a Tertiary Care Hospital in Korea

Kang, Bo Hyoung,Jo, Kyung-Wook,Shim, Tae Sun The Korean Academy of Tuberculosis and Respiratory 2017 Tuberculosis and Respiratory Diseases Vol.80 No.2

Background: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. Methods: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. Results: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study. The most common reasons for fluoroquinolone use were adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance (23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the most commonly administered fluoroquinolone, followed by levofloxacin (36.3%, 82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The most common fluoroquinolone-related adverse events were gastrointestinal problems (3.5%, 8/226). There were no significant differences in the treatment success rate between the fluoroquinolone and fluoroquinolone-$na{\ddot{i}}ve$ groups (78.3% vs. 78.4%, respectively). Conclusion: At our institution, fluoroquinolones are commonly used for the treatment of both multidrug-resistant tuberculosis and susceptible tuberculosis, especially as a substitute for adverse event-related drugs. Considering the low adverse event rates and the comparable treatment success rates, fluoroquinolones seem to be an invaluable drug for the treatment of tuberculosis.

Utility of Routine Culture for Tuberculosis from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in a Tuberculosis Endemic Country

Hong, Ji-Young,Jung, Ji-Ye,Kang, Young-Ae,Park, Byung-Hoon,Jung, Won-Jai,Lee, Su-Hwan,Kim, Song-Yee,Lee, Sang-Kook,Chung, Kyung-Soo,Park, Seon-Cheol,Kim, Eun-Young,Lim, Ju-Eun,Kim, Se-Kyu,Chang, Joon The Korean Academy of Tuberculosis and Respiratory 2011 Tuberculosis and Respiratory Diseases Vol.71 No.6

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique developed to allow mediastinal staging of lung cancer and also to evaluate intrathoracic lymphadenopathy. In a tuberculosis-endemic area, tuberculosis should be considered as an etiology of mediastinal lymphadenopathy. The aim of this study was to investigate the utility of the routine culture for tuberculosis from specimens of EBUS-TBNA. Methods: We prospectively performed routine culture for tuberculosis from aspiration or core biopsy specimens got from 86 patients who had undergone EBUS-TBNA due to mediastinal lymphadenopathy between March 2010 and March 2011. Results: A total of 135 lymph node aspiration and 118 core biopsy specimens were included in this analysis. We confirmed the malignancy in 62 (72.9%), tuberculosis in 7 (8.1%), sarcoidosis in 7 (8.1%), asperogillosis in 2 (2.3%) and pneumoconiosis in 2 (2.3%) patients. One lung cancer patient had pulmonary tuberculosis coincidentally and 5 patients had unknown lymphadenopathy. The number of positive culture for Mycobacterium tuberculsosis by EBUS-TBNA is 2 (1.5%) from 135 lymph node aspiration specimens and 2 (1.7%) from 118 core biopsy specimens. Out of eight patients confirmed with tuberculosis, only one patient had positive mycobacterial culture of aspiration specimen from EBUS-TBNA without histopathologic diagnosis. Conclusion: These results propose that routine culture for tuberculosis from EBUS-TBNA may not provide additional information for the diagnosis of coincident tuberculous lymphadenitis. However, if there is any possibility of tuberculous lymphadenopathy or pulmonary tuberculosis, it should be considered to perform EBUS-TBNA in patients who have negative sputum AFB smears or no sputum production.

Issues Related to the Updated 2014 Korean Guidelines for Tuberculosis

Park, Jae Seuk The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.1

Tuberculosis (TB) remains a major public health problem in South Korea. The Joint Committee for the Development of Korean Guidelines for Tuberculosis published the Korean Guidelines for Tuberculosis in 2011 to provide evidence-based practical recommendations to health care workers caring for patients with TB in South Korea. After reviewing recent national and international scientific data on TB, the committee updated the Korean guidelines for TB in 2014. This article presents some practical issues related to the 2014 updated guidelines: namely use of the Mycobacterium tuberculosis-polymerase chain reaction assay and the Xpert MTB/RIF assay in the diagnosis of TB, as well as medical treatment for patients with multidrug-resistant TB.

Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates

Hlaing, Yin Moe,Tongtawe, Pongsri,Tapchaisri, Pramuan,Thanongsaksrikul, Jeeraphong,Thawornwan, Unchana,Archanachan, Buppa,Srimanote, Potjanee The Korean Academy of Tuberculosis and Respiratory 2017 Tuberculosis and Respiratory Diseases Vol.80 No.2

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

Comparing Two Mycobacterium tuberculosis Genomes from Chinese Immigrants with Native Genomes Using Mauve Alignments

Ryoo, Sungweon,Lee, Jeongsoo,Oh, Jee Youn,Kim, Byeong Ki,Kim, Young,Kim, Je Hyeong,Shin, Chol,Lee, Seung Heon The Korean Academy of Tuberculosis and Respiratory 2018 Tuberculosis and Respiratory Diseases Vol.81 No.3

Background: The number of immigrants with tuberculosis (TB) increases each year in South Korea. Determining the transmission dynamics based on whole genome sequencing (WGS) to cluster the strains has been challenging. Methods: WGS, annotation refinement, and orthology assignment for the GenBank accession number acquisition were performed on two clinical isolates from Chinese immigrants. In addition, the genomes of the two isolates were compared with the genomes of Mycobacterium tuberculosis isolates, from two native Korean and five native Chinese individuals using a phylogenetic topology tree based on the Multiple Alignment of Conserved Genomic Sequence with Rearrangements (Mauve) package. Results: The newly assigned accession numbers for two clinical isolates were CP020381.2 (a Korean-Chinese from Yanbian Province) and CP022014.1 (a Chinese from Shandong Province), respectively. Mauve alignment classified all nine TB isolates into a discriminative collinear set with matched regions. The phylogenetic analysis revealed a rooted phylogenetic tree grouping the nine strains into two lineages: strains from Chinese individuals and strains from Korean individuals. Conclusion: Phylogenetic trees based on the Mauve alignments were supposed to be useful in revealing the dynamics of TB transmission from immigrants in South Korea, which can provide valuable information for scaling up the TB screening policy for immigrants.

Agranulocytosis Induced by Ethambutol in a Patient with Pulmonary Tuberculosis

Moon, Kyoung Min,Han, Min Soo,Chung, So Hee,Kim, Ju Ri,Kim, Jin Young,Jung, Sun Young,Cho, Yongseon The Korean Academy of Tuberculosis and Respiratory 2015 Tuberculosis and Respiratory Diseases Vol.78 No.2

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of $70/{\mu}L$. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea

Yun, Yeo Jun,Lee, Jong Seok,Yoo, Je Chul,Cho, Eunjin,Park, Dahee,Kook, Yoon-Hoh,Lee, Keun Hwa The Korean Academy of Tuberculosis and Respiratory 2018 Tuberculosis and Respiratory Diseases Vol.81 No.3

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

Pandemic Influenza (H1N1) and Mycobacterium tuberculosis Co-infection

Park, Yehyun,Chin, Bum Sik,Han, Sang Hoon,Yun, Yujung,Kim, Young Ju,Choi, Jun Yong,Kim, Chang Oh,Song, Young Goo,Kim, June Myung The Korean Academy of Tuberculosis and Respiratory 2014 Tuberculosis and Respiratory Diseases Vol.76 No.2

We hereby observe four co-infection cases of pandemic influenza H1N1 and Mycobacterium tuberculosis with various clinical presentations. It may be prudent to consider M. tuberculosis co-infections when patients with pandemic influenza reveal unusual clinical features that do not improve despite appropriate treatments against the influenza, especially in Korea, in the endemic areas of M. tuberculosis.

Urine Cotinine for Assessing Tobacco Smoke Exposure in Korean: Analysis of the Korea National Health and Nutrition Examination Survey (KNHANES)

Jung, Sungmo,Lee, In Seon,Kim, Sae Byol,Moon, Chan Soo,Jung, Ji Ye,Kang, Young Ae,Park, Moo Suk,Kim, Young Sam,Kim, Se Kyu,Chang, Joon,Kim, Eun Young The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.73 No.4

Background: The level of urine cotinine is an indicator of tobacco smoke exposure. The purpose of this study is to investigate urine cotinine for the purpose of assessing the smoking status of Korean smokers and non-smokers exposed to tobacco smoke. Methods: The subjects were identified from the 2007-2009 and the 2010 data sets of the Korea National Health and Nutrition Examination Survey (KNHANES). They were assigned as non-smokers, current smokers and ex-smokers. Non-smokers were also divided into three subset groups according to the duration of smoke exposure. Each group was stratified by gender prior to analysis. Results: The median value of urine cotinine in the male current smokers was 1,221.93 ng/mL which was the highest among all groups. The difference between levels of urine cotinine for male and the female groups was statistically significant (p<0.01). In the female group, passive smoke exposure groups reported higher urine cotinine levels than non-exposure groups (p=0.01). The cutoff point for the discrimination of current smokers from non-smokers was 95.6 ng/mL in males and 96.8 ng/mL in females. The sensitivity and specificity were 95.2% and 97.1%, respectively, in males, 96.1% and 96.5% in females. However, the determination of urine cotinine level was not useful in distinguishing between passive smoke exposure groups and non-exposure groups. Conclusion: Urine cotinine concentration is a useful biomarker for discriminating non-smokers from current smokers. However, careful interpretation is necessary for assessing passive smoke exposure by urine cotinine concentration.

Diagnosis of Pulmonary Tuberculosis: Recent Advances and Diagnostic Algorithms

Ryu, Yon Ju The Korean Academy of Tuberculosis and Respiratory 2015 Tuberculosis and Respiratory Diseases Vol.78 No.2

Pulmonary tuberculosis (TB) persists as a great public health problem in Korea. Increases in the overall age of the population and the rise of drug-resistant TB have reinforced the need for rapid diagnostic improvements and new modalities to detect TB and drug-resistant TB, as well as to improve TB control. Standard guidelines and recent advances for diagnosing pulmonary TB are summarized in this article. An early and accurate diagnosis of pulmonary TB should be established using chest X-ray, sputum microscopy, culture in both liquid and solid media, and nucleic acid amplification. Chest computed tomography, histopathological examination of biopsy samples, and new molecular diagnostic tests can be used for earlier and improved diagnoses, especially in patients with smear-negative pulmonary TB or clinically-diagnosed TB and drug-resistant TB.