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.

Risk Factors Related with Mortality in Patient with Pulmonary Tuberculosis

Kim, Chong Whan,Kim, Sang-Ha,Lee, Shun Nyung,Lee, Seok Jeong,Lee, Myoung Kyu,Lee, Ji-Ho,Shin, Kye Chul,Yong, Suk Joong,Lee, Won Yeon The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.73 No.1

Background: The prevalence rate of pulmonary tuberculosis (PTB) is steadily decreasing in South Korea. However, PTB is a disease with relatively high mortality and morbidity rates throughout Korea. Although there are many studies and statistics about the risk factors of PTB mortality in many countries, there are only a limited number of domestic papers on this topic. The aim of this study is to determine predictive factors for mortality among in-hospital patients associated with PTB. Methods: From December 2006 to January 2011, we reviewed medical records of 2,122 adult patients diagnosed with tuberculosis at a single tertiary hospital in a suburban area. In this study period, 960 patients were diagnosed with PTB by positive Acid fast bacilli smear and/or mycobacterial culture of the respiratory specimen. We compared the groups of patients deceased and patients discharged alive with PTB. The number of dead patients was 82 (47 males, 35 females). Results: Mortality was significantly associated with increased values of white blood cells (WBC), blood urine nitrogen (BUN), creatinine, C-reactive protein (CRP), numbers of involved lung field, and length of hospitalization. Also, it was associated with the decreased values of hemoglobin, lymphocyte, sodium, albumin, and cholesterol. Furthermore, admission through the emergency department, initial intensive care unit admission, and drug resistant PTB affected mortality in PTB patients. Independent predictors associated with PTB mortality are BUN, initial intensive care unit care, and admission during treatment of tuberculosis. Conclusion: In our study, mortality of pulmonary tuberculosis was related with parameters associated with nutritional status, disease severity at the time of admission, and drug resistance.

Dilemma of Asthma Treatment in Mild Patients

Cho, You Sook,Oh, Yeon-Mok The Korean Academy of Tuberculosis and Respiratory 2019 Tuberculosis and Respiratory Diseases Vol.82 No.3

Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting ${\beta}$-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as "persistent controller users," should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid-onset long-acting ${\beta}$-agonists instead of using a SABA alone or with low-dose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.

Development of Prediction Equation of Diffusing Capacity of Lung for Koreans

Hwang, Yong Il,Park, Yong Bum,Yoon, Hyoung Kyu,Lim, Seong Yong,Kim, Tae-Hyung,Park, Joo Hun,Lee, Won-Yeon,Park, Seong Ju,Lee, Sei Won,Kim, Woo Jin,Kim, Ki Uk,Shin, Kyeong Cheol,Kim, Do Jin,Kim, Hui Ju The Korean Academy of Tuberculosis and Respiratory 2018 Tuberculosis and Respiratory Diseases Vol.81 No.1

Background: The diffusing capacity of the lung is influenced by multiple factors such as age, sex, height, weight, ethnicity and smoking status. Although a prediction equation for the diffusing capacity of Korea was proposed in the mid-1980s, this equation is not used currently. The aim of this study was to develop a new prediction equation for the diffusing capacity for Koreans. Methods: Using the data of the Korean National Health and Nutrition Examination Survey, a total of 140 nonsmokers with normal chest X-rays were enrolled in this study. Results: Using linear regression analysis, a new predicting equation for diffusing capacity was developed. For men, the following new equations were developed: carbon monoxide diffusing capacity (DLco)=-10.4433-0.1434${\times}$age (year)+0.2482${\times}$heights (cm); DLco/alveolar volume (VA)=6.01507-0.02374${\times}$age (year)-0.00233${\times}$heights (cm). For women the prediction equations were described as followed: DLco=-12.8895-0.0532${\times}$age (year)+0.2145${\times}$heights (cm) and DLco/VA=7.69516-0.02219${\times}$age (year)-0.01377${\times}$heights (cm). All equations were internally validated by k-fold cross validation method. Conclusion: In this study, we developed new prediction equations for the diffusing capacity of the lungs of Koreans. A further study is needed to validate the new predicting equation for diffusing capacity.

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.

Association of Serum Vitamin D Levels with Bacterial Load in Pulmonary Tuberculosis Patients

Yuvaraj, B.,Sridhar, M.G.,Kumar, S. Vinod,Kadhiravan, T. The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3

Background: Vitamin D is known to have diverse effects on various systems in the body. There is evidence to suggest that a link exists between the serum vitamin D status and tuberculosis. The present study was designed to assess the alterations in serum 25-hydroxyvitamin D levels in newly diagnosed sputum acid fast bacilli (AFB) positive pulmonary tuberculosis patients and to study the association, if any, between serum vitamin D levels and different levels of sputum smear positivity. Methods: Serum 25-hydroxyvitamin D levels were estimated in 65 sputum AFB positive pulmonary tuberculosis patients and 65 age and gender-matched healthy controls. Results: The levels of serum 25 hydroxy-vitamin D in tuberculosis patients were not statistically different from the levels of serum 25 hydroxy-vitamin D in healthy controls. However, among patients with pulmonary tuberculosis, there was a significant negative correlation between the levels of serum 25 hydroxy-vitamin D and levels of sputum positivity. Conclusion: Serum vitamin D levels negatively correlates with bacterial load in patients with active pulmonary tuberculosis.

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.

Factors Associated with Indeterminate and False Negative Results of QuantiFERON-TB Gold In-Tube Test in Active Tuberculosis

Cho, Ki-Won,Cho, Eun-Ha,Kwon, Soo-Hoon,Im, Sang-Hyuk,Sohn, In,Song, Sook-Hee,Kim, Hye-Ok,Kim, Su-Hyun The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.72 No.5

Background: The sensitivities and specificities of interferon-gamma release assays (IGRAs) vary among different population studies, and the data on the routine use of IGRAs are limited. The aim of this study was to evaluate the role of QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of active tuberculosis. Methods: We conducted a prospective study, enrolling 77 patients with suspected pulmonary tuberculosis (TB), at a secondary care teaching hospital in Seoul. Results: In total, 12 (15.6%) patients showed indeterminate results due to positive control failure on the QFT-GIT test. Indeterminate results were significantly associated with the elderly, history of the intensive care unit stay, lymphocytopenia, especially low CD4 count, increased C-reactive protein and decreased protein levels. Of the 77 patients, 44 (57.1%) were diagnosed with active pulmonary tuberculosis, and the percentage of false negative results of the QFT-GIT was 36.4% (vs. 31.8% with TST). In the TB group with >65 years old (n=12), the proportions of the indeterminate (33.3% vs. 3.1%) and the false negative results (58.3% vs. 25.0%) of the QFT-GIT were significantly higher than in the younger TB group (n=32). Conclusion: Indeterminate and false negative results of QFT-GIT test were not infrequent in tuberculosis, especially in the elderly. Care should be considered for the interpretation with the elderly, immunocompromised, chronic and severely diseased patients.