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INTRODUCTION Screening and treatment of latent tuberculosis infections (LTBI) are required before starting biologics in patients with immune-mediated inflammatory diseases (IMIDs). This study aimed to assess the safety of LTBI treatment in older patients with IMIDs. METHODS The medical records of 916 patients treated for LTBI before the start of biologics for IMIDs between January 2004 and December 2018 were reviewed. The safety profiles of LTBI treatment were retrospectively compared according to age. RESULTS Among the 916 patients, 201 were aged > 60 years (older age group). The older age group showed female predominance, more frequent history of previous tuberculosis, and more comorbidities, and received biologics mainly for rheumatoid arthritis. Most patients (74.0%) took isoniazid and rifampicin daily for 3 months. The treatment completion rate was 90.4% in the overall population and was lower in the older age group (91.9% vs. 85.1%, P = 0.005). Adverse drug events were more frequent in the older age group (22.9% vs. 9.8%, P

The most important thing for the management of drug susceptible pulmonary tuberculosis is to diagnose active pulmonary tuberculosis as soon as possible and prevent the occurrence of new patients through appropriate treatment. Therefore, it should be a priority to quickly detect tuberculosis mycobacterium and quickly exclude drug-resistant tuberculosis before treatment begins. To this end, recent guidelines recommend the general use of Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) tests, Xpert MTB/RIF tests, and rapid sensitivity tests through line probe assay (LPA). In addition, if the results of the test are positive, it is important to establish an in-hospital reporting system so that rapid reporting can be made. The treatment principle for drug susceptible pulmonary tuberculosis is 2 months of initial intensive phase (isoniazid, rifampin, ethambutol, pyrazinamide) followed by 4 months of maintenance phase (isoniazid, rifampin). Despite global efforts to shorten the duration of the treatment, the treatment of drug susceptible pulmonary tuberculosis has not changed for more than 35 years, and problems such as increased side effects and reduced drug adherence are serious obstacles to tuberculosis management. Therefore, efforts have been steadily made to shorten the treatment period through the combination of new drugs worldwide, and after many failures, they are finally paying off. A recently published Study 31/A5349 study found that 4 months short-term regimen using rifapentine (RPT) and moxifloxacin (MFX) demonstrated non-inferiority in existing standard regimen, as the result, a revision of World Health Organization guidelines is scheduled that 4 months short-term regimen using RPT and MFX may be an alternative. However, it is unlikely that RPT/MFX 4 months short-term regimen will be applied immediately in Korea because the use of RPT is currently limited in Korea due to the high frequency of side effects.

Background Although spontaneous sputum conversion can occur in noncavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex lung disease (MAC-LD), little is known about redevelopment after spontaneous conversion. We investigated the redevelopment phenomenon after spontaneous sputum conversion in patients with NC-NB MAC-LD. Material and methods Among patients diagnosed with NC-NB MAC-LD between 2000 and 2013, 140 patients who experienced spontaneous sputum conversion, and whose follow-up duration after conversion was ≥6 months, were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. Results Of the 140 patients, 34 (24.3%) underwent redevelopment during the median follow-up period of 71.0 months (interquartile range [IQR], 58.8–87.5). Redevelopment occurred at a median interval of 25.0 months (IQR, 11.5–41.8) after spontaneous sputum conversion. The mean age of the 34 patients with redevelopment was 63.6 years, and 73.5% were women. No statistically significant differences in clinical characteristics were noted between the 34 patients with redevelopment and those with persistent conversion. Among the 34 patients with redevelopment, 6 received treatment at a median interval of 8 months (IQR, 1.5–16.8) after redevelopment. No significant differences in clinical characteristics were noted between the six treated and 28 untreated patients. Conclusion At least approximately 24% of patients with spontaneous sputum conversion in NC-NB MAC-LD had redevelopment, and a portion of them required treatment. These findings suggest that long-term follow-up is necessary for patients with NC-NB MAC-LD, even those who experience spontaneous sputum conversion.

High-risk healthcare workers (HCWs) are often screened for latent tuberculosis infection (LTBI) using QuantiFERON tests (QFTs), with annual serial tests often showing reversion from positive to negative results. We assessed the frequency of and risk factors for reversion of QFTs in HCWs in an intermediate-tuberculosis burden country.We enrolled high-risk HCWs at a tertiary-care hospital in South Korea, who were assessed by QFTs at least twice between 2017 and 2019.Of the 1870 HCWs screened, 1542 (82%) had persistent negative results, 229 (12%) had persistent positive results, 53 (3%) showed reversion, and 46 (2%) showed conversion from negative to positive. Multivariate analysis comparing the characteristics of the 229 HCWs with persistent positive results and the 53 who experienced reversion showed that older age (adjusted odds ratio (aOR): 0.96; 95% confidence interval (CI): 0.92-0.99), male sex (aOR: 0.29; 95% CI: 0.11-0.78) and high (≥0.70 IU/mL) baseline QFT results (aOR: 0.15; 95% CI: 0.07-0.31) were inversely associated with reversion. Using an ROC curve-derived cut-off of0.738 IU/mL, the area under the curve was 0.79. Of 53 HCWs with reversion, 36 (78%) had below 0.738 IU/mL of baseline QFT, while 181 (79%) of 229 HCWs without reversion had above 0.738 IU/mL of baseline QFT.Reversion during serial testing is unlikely in HCWs who are male, older in age, and have higher baseline QFT results. Serial testing without LTBI treatment may be indicated in HCWs who are female, younger and, especially, have lower QFT results.

Background We encountered some cases of early-onset tuberculosis (TB) after liver transplant (LT), leading to further transmission to other immunocompromised patients. Therefore, we investigated the clinical characteristics and risk factors of early-onset TB after LT. Methods All adult patients with TB after LT from 1996 to 2019 were retrospectively enrolled. Our hospital did not screen for latent TB infection (LTBI) in LT recipients because of concerns regarding the potential hepatotoxicity of anti-TB medication. Patients were categorized into 2 groups based on the TB onset time after LT: early-onset TB (≤2 months) and late-onset TB (>2 months). Results Of 4301 LT recipients, 91 patients developed TB after LT (2.1%). The median time from LT to TB development was 9.4 months. Of these 91 patients, 11 were classified as having early-onset TB (12.1%). Patients with early-onset TB had a greater pretransplant TB history than patients with late-onset TB (36.4% vs 11.3%, P = .048). Conclusion This unusual early-onset TB was more common in patients with a pretransplant TB history, suggesting the possibility of missed TB or full manifestation of the indolent course of TB after LT. Therefore, LT recipients with a pretransplant TB history should undergo thorough screening for active TB and consider prophylaxis.

Background A few studies have mentioned that post-bronchoscopy sputum (PBS) could improve the diagnostic yield in pauci-bacillary pulmonary tuberculosis (PTB). Therefore, we evaluated the diagnostic yield of PBS for diagnosing pauci-bacillaryPTB. Methods Clinical data of immunocompromised adult patients with pauci-bacillary PTB were retrospectively retrieved at a tertiary hospital in Seoul, South Korea over a 5-year period. We analyzed patients who underwent bronchoscopy examinations for diagnosing pauci-bacillary PTB. Results Ninety patients were finally analyzed. Of these patients, 76 patients were tested with PBS. Six (8%) of these patients had positive results on AFB smear of PBS alone. Additionally, 52 patients (68%) had positive results on mycobacterial culture and 12 (16%) had positive results on mycobacterial culture of PBS exclusively. Therefore, in this study population, a total of 18 patients (20%) were finally diagnosed as having PTB with PBS results only, even though AFB smear microscopy and culture of other specimens had negative results. Conclusions PBS could improve the diagnostic yield by 20% when diagnosing pauci-bacillary PTB. In addition, about 8% of the patients could be diagnosed rapidly because of AFB smear microscopy positivity for PBS. Therefore, PBS use should be considered as a complementary diagnostic approach in patients with suspected pauci-bacillary PTB.

Background The timeline of infections after lung transplantation has been changed with the introduction of new immunosuppressants and prophylaxis strategies. The study aimed to investigate the epidemiological characteristics of infectious diseases after lung transplantation in the current era. Materials and methods All patients who underwent lung or heart-lung transplantation at our institution between October 29, 2008 and April 3, 2019 were enrolled. We retrospectively reviewed the patients' medical records till April 2, 2020. Results In total, 100 consecutive lung transplant recipients were enrolled. The median follow-up period was 28 months after lung transplantation. A total of 127 post-lung transplantation bacterial infections occurred. Catheter-related bloodstream infection (25/84, 29.8%) was the most common within 6 months and pneumonia (23/43, 53.5%) was the most common after 6 months. Most episodes (35/40, 87.5%) of respiratory viral infections occurred after 6 months, mainly as upper respiratory infections. The remaining episodes (5/40, 12.5%) mostly manifested as lower respiratory tract infections. Seventy cytomegalovirus infections observed in 43 patients were divided into 23 episodes occurring before and 47 episodes occurring after discontinuing prophylaxis. Of 10 episodes of cytomegalovirus disease, four occurred during prophylaxis and six occurred after prophylaxis. Of 23 episodes of post-lung transplantation fungal infection, 7 were aspergillosis and all occurred after the discontinuation of prophylaxis. Conclusion Lung transplant recipients experienced a high burden of infection even after 6 months, especially after the end of the prophylaxis period. Therefore, these patients should be continued to be monitored long-term for infectious disease.

Objective Rifampin is known to influence the pharmacokinetics of tofacitinib owing to drug interactions. The aim of this study was to determine the efficacy of tofacitinib on co-administration with rifampin in rheumatoid arthritis (RA) patients. Methods Biologic-naive RA patients treated with tofacitinib were selected, and electronic medical reports were reviewed retrospectively. All patients underwent screening for latent tuberculosis infection (LTBI) before starting tofacitinib, and patients with positive results were treated to prevent progression to active tuberculosis. To evaluate the efficacy of tofacitinib with or without rifampin, the discontinuation rates of tofacitinib were examined during the first 6 months. Kaplan–Meier analysis was used to construct cumulative discontinuation curves, and comparisons were performed using the log-rank test. Results Among 81 patients who starting tofacitinib, 21 were LTBI-positive and 18 were administered rifampin concomitantly with tofacitinib. Additionally, 14 of the 81 patients (17.3%) discontinued tofacitinib during the follow-up, and 7 patients discontinued tofacitinib because of uncontrolled RA activity. The discontinuation rates of tofacitinib within the first 6 months were significantly higher in patients treated with rifampin for LTBI than in those not treated with rifampin (lack of efficacy: 24.7% vs. 5.1%, P Conclusions Discontinuation rates were higher in RA patients who started tofacitinib during chemoprophylaxis involving rifampin than in those who did not receive rifampin. Physicians should be aware that the efficacy of tofacitinib could be decreased by chemoprophylactic regimens for tuberculosis.

Objectives This study aimed to compare the discontinuation rates attributed to adverse events and treatment outcomes between clarithromycin (CLR) and azithromycin (AZM) in patients with Mycobacterium avium complex lung disease (MAC-LD). Methods Among patients diagnosed with MAC-LD during 2001–2013, 560 for whom treatment was initiated as a guideline-based therapy until May 2018 were selected for adverse event analysis. Of them, 316 who underwent treatment for ≥12 months were selected for outcome analysis. Their medical records were retrospectively reviewed. The discontinuation and treatment success rates were analysed after adjustments using the inverse probability of treatment weighted (IPTW) method. Results Among the 560 patients, 466 (83.2%) and 94 (16.8%) started CLR-containing and AZM-containing regimens, respectively. The IPTW method using propensity scoring revealed that the discontinuation rate attributed to adverse events was significantly higher with CLR than AZM use (24.6% vs. 9.6%; P = 0.001). The overall treatment success rate of the 316 patients who received guideline-based therapy for ≥12 months was 83.2%. Analysis adjusted by the IPTW method showed no significant difference in the treatment success rate between the use of CLR and AZM. Furthermore, 1-year and 3-year recurrence rates were similar with the two drugs (6.8% vs. 6.0%; P > 0.999 and 31.0% vs. 37.5%; P = 0.482, respectively). Conclusions These findings suggest that an AZM-containing regimen may be the better initial treatment choice for MAC-LD as it resulted in lesser discontinuation rates attributed to adverse events while offering similar patient outcomes when compared with CLR.

Background/aims Although re-evaluation of radiographic follow-up after 2 to 3 months of therapy is recommended for patients administered anti-tuberculosis medication owing to suspected pulmonary tuberculosis, reported findings are limited. Therefore, this study aimed to investigate changes in 1- and 2-month chest X-ray (CXR) findings after the treatment initiation and compared them according to the final diagnosis of tuberculosis or non-tuberculosis. Methods Patients who started anti-tuberculosis medication for suspected pulmonary tuberculosis were selected at a tertiary referral hospital in South Korea between January 2012 and December 2015. Changes in the 1- and 2-month CXR findings were classified as improved, unchanged, and aggravated. Results Among the 120 patients enrolled in the 1-month CXR group, 76 (63.3%) had the final diagnosis of tuberculosis. Comparison between the 1-month CXR changes and diagnosis showed that the final diagnosis was tuberculosis in 81.8% (45/55), 50.0% (26/52), and 38.5% (5/13) of patients whose 1-month CXR was improved, unchanged, and aggravated, respectively. In the 2-month CXR group, 167 patients were enrolled, and 139 (83.2%) of them were diagnosed with tuberculosis. Tuberculosis was the final diagnosis in 92.6% (100/108), 70.0% (35/50), and 44.4% (4/9) patients with improved, unchanged, and aggravated 2-month CXR findings, respectively. In patients with the final diagnosis of non-tuberculosis, nontuberculous mycobacteria and malignancy were the most common causes of improved and aggravated 1- and 2-month CXR findings, respectively. Conclusion Two-month CXR findings were of limited value for deciding on whether to continue anti-tuberculosis treatment. One-month CXR findings could help determine the need for further work-up.

Right heart decompensation is a fatal complication in patients with respiratory failure, particularly in those transitioned to lung transplantation using veno-venous extracorporeal membrane oxygenation (V-V ECMO). In these patients, veno-arterial (V-A ECMO) or veno-arterialvenous extracorporeal membrane oxygenation (V-AV ECMO) is used to support both cardiac and respiratory function. However, these processes may increase the risk of device-related complications such as bleeding, thromboembolism, and limb ischemia. In the present case, a 64-year-old male patient with idiopathic pulmonary fibrosis developed respiratory failure and commenced treatment with V-V ECMO as a bridge to lung transplantation. Unfortunately, the patient developed right heart decompensation and required both cardiac and respiratory support during treatment with V-V ECMO. Instead of adding arterial cannulation, he was switched to a novel configuration, a right ventricular assist device with an oxygenator (Oxy- RVAD) using ECMO, with drainage cannulation from the femoral vein and return cannulation to the main pulmonary artery. The patient was successfully bridged to lung transplantation without serious complications after 10 days of Oxy-RVAD support. To the best of our knowledge, this is an extreme rare and challenging case of Oxy-RVAD using ECMO in a patient successfully bridged to lung transplantation.

BACKGROUND: The recommended treatment duration for non-cavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex (MAC) lung disease (LD) is at least 12 months after culture conversion, but evidence supporting this is limited. This study investigated whether treatment for less than 12 months after culture conversion is acceptable in terms of recurrence rate. METHODS: The study enrolled the patients diagnosed with NC-NB MAC LD between 2001 and 2014 at a tertiary referral center in South Korea who received the standard treatment for at least 9 months after culture conversion up to October 2018. The patients were divided into a shorter treatment group (9–11 months after culture conversion) and a standard treatment group (≥12 months). RESULTS: Of the 228 patients enrolled, 59 (25.9%) were treated for 9–11 months after culture conversion and 169 (74.1%) for ≥12 months. The mean treatment durations after culture conversion in the shorter and standard treatment groups were 11.1 and 13.8 months, respectively (P

Background: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii ; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants’ clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

Purpose We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. Materials and methods LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. Results Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. Conclusion The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.

Bedaquiline and delamanid were recently approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Korea. A treatment duration of 24 weeks was established based on phase 2 clinical trial data, although the combined use of these two drugs is typically not recommended because it may exaggerate QT prolongation. Here, we present a case of prolonged treatment (48 weeks) with a combination of bedaquiline and delamanid for pulmonary MDR-TB. The patient had previously been diagnosed with extensively drug-resistant TB but had been left untreated for the past 9 years due to a shortage of effective drugs. A combination of bedaquiline and delamanid successfully treated MDR-TB, highlighting the potential efficacy of these drugs for patients with drug-resistant TB infections. (Korean J Med 2019;94:294-298)

Purpose We aimed to investigate the natural history of non-cavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex (MAC) lung disease (LD). Methods Among all patients diagnosed with NC-NB MAC LD between March 2000 and December 2013, 551 patients who were followed until December 2017 were enrolled at a tertiary referral center in South Korea. Patients were subdivided into progressive and stationary groups, depending on whether treatment was initiated within 3 years after diagnosis. We investigated the proportion of patients not receiving anti-MAC treatment within 3 years after the diagnosis. The rate for spontaneous sputum conversion in the untreated group was also calculated. Results The mean age of 551 patients was 61.1 years. During the median 5.8 years of follow-up, 323 (58.6%) patients received treatment within 3 years (progressive group), whereas the remaining 228 (41.4%) patients did not (stationary group). Multivariate analysis revealed that age ≤ 60 years, a positive sputum smear, the presence of systemic symptoms, body mass index >18.5 kg/m2, and the involvement of ≥ 4 lobes were predictors of receiving treatment. Additionally, during the median of 5.0 years follow-up, spontaneous sputum conversion occurred in 52.2% of patients who did not receive treatment. Conclusions Among patients diagnosed with NC-NB MAC LD, approximately 40% did not receive antibiotic treatment within 3 years of diagnosis. Moreover, about 50% of untreated patients experienced spontaneous sputum conversion.

Background Current guidelines recommend a susceptibility-based regimen for Mycobacterium abscessus subspecies abscessus pulmonary disease (MAB-PD), but the evidence is weak. We aimed to investigate the association between treatment outcomes and in vitro drug susceptibility to injectable antibiotics in MAB-PD patients. Methods We enrolled MAB-PD patients treated with intravenous amikacin and beta-lactams for ≥4 weeks at 4 referral hospitals in Seoul, South Korea. Culture conversion and microbiological cure at 1 year were evaluated based on susceptibility to injectable antibiotics among patients treated with those antibiotics for ≥2 weeks. Results A total of 82 patients were analyzed. The mean age was 58.7 years, and 65.9% were women. Sputum culture conversion and microbiological cure were achieved in 52.4% and 41.5% of patients, respectively. Amikacin was the most common agent to which the M. abscessus subspecies abscessus isolates were susceptible (81.7%); 9.8% and 24.0% of the isolates were resistant to cefoxitin and imipenem, respectively. The clarithromycin-inducible resistance (IR) group (n = 65) had a lower microbiological cure rate than the clarithromycin-susceptible group (35.4% vs 64.7%). The treatment outcomes appeared to be similar regardless of in vitro susceptibility results with regard to intravenous amikacin, cefoxitin, imipenem, and moxifloxacin. In the subgroup analysis of the clarithromycin-IR group, the treatment outcomes did not differ according to antibiotic susceptibility. Conclusions We did not find evidence supporting the use of susceptibility-based treatment with intravenous amikacin and beta-lactams in patients with MAB-PD. Further research is required., Current guidelines recommend a susceptibility-based regimen for Mycobacterium abscessus subspecies abscessus pulmonary disease. In this retrospective cohort study, the treatment outcomes appeared to be similar regardless of in vitro susceptibility results with regard to amikacin, cefoxitin and imipenem.

Considering the risk of reactivation of latent tuberculosis infection (LTBI), not only before starting tumor necrosis factor inhibitors but also before non-TNF inhibitor therapy, LTBI screening is routinely recommended for patients with inflammatory bowel disease (IBD). However, data on the positive conversion of LTBI test results during non-TNF inhibitor therapy are scarce. Among IBD patients treated with vedolizumab and/or ustekinumab, a total of 91 patients who had negative baseline interferon-gamma release assay (IGRA) results, assessed by QuantiFERON®-TB Gold In-tube or QuantiFERON®-TB Gold Plus, were enrolled. Serial LTBI test results after starting non-TNF inhibitor therapy were collected, and patients' clinical characteristics were analyzed. Positive IGRA conversion was observed in six of 91 patients (6.6%). The cumulative IGRA conversion–free survival rates after starting therapy were 97.7% after 1 year and 86.7% after 2 years. Ulcerative colitis was more common among converters compared with non-converters (66.7 vs. 23.5%, P = 0.040). Among six converters, four had been treated with vedolizumab, one with ustekinumab, and the other with vedolizumab followed by ustekinumab. All six patients had been previously exposed to TNF inhibitors before non-TNF inhibitor therapy: five to infliximab and one to both infliximab and adalimumab. After positive IGRA conversion, none of the six converters developed active tuberculosis while maintaining non-TNF inhibitor therapy (median 6.8 months, range 0.4–32.1 months). Positive IGRA conversion among IBD patients treated with vedolizumab and/or ustekinumab appears to occur somewhat frequently, but its clinical implications remain to be elucidated.

In this study, we aimed to assess the performance of the Xpert MTB/RIF assay for the detection of pulmonary tuberculosis compared to the acid-fast bacilli (AFB) smear and culture analysis, and the incidence of rifampin resistance using the drug susceptibility test. The specimens referred for AFB smear and culture analysis and Xpert MTB/RIF assay from April 2015 to March 2018 were retrospectively reviewed. The sensitivity, specificity, and mean cycle threshold (Ct) values obtained in Xpert MTB/RIF assay and for rifampin resistance were analyzed. The results of Xpert MTB/RIF assay for pulmonary tuberculosis were evaluated based on the AFB smear grade. Among 3,840 specimens, 491 were positive in Xpert MTB/RIF assay and 626 in culture analysis. The sensitivity and specificity of Xpert MTB/RIF assay were 75.6% and 99.4%, respectively. The sensitivity of Xpert MTB/RIF assay for smear-positive/culture-positive specimens was 98.6% and that of smear-negative and -trace/culture-positive specimens was 63.1%. The positivity of Xpert MTB/RIF assay for culture-positive specimens was 89.9%, 98.6%, 95.7%, 100.0%, and 100.0% for the smear grades trace, 1+, 2+, 3+, 4+, respectively. The Ct values of 491 specimens significantly decreased as the AFB smear grade increased (P < 0.0001). The Ct values of smear-positive, -trace, and -negative specimens were 21.7 ± 4.2, 26.5 ± 3.9, and 27.4 ± 3.6, respectively. Rifampin resistance evaluated using Xpert MTB/RIF assay and culture analysis exhibited a correlation of 98.3%. The region covered by probe E was the most frequently mutated region (50.0%). Xpert MTB/RIF assay demonstrated reliable performance in detecting pulmonary tuberculosis from smear-positive and culture-positive specimens; however, further improvements are still required to detect smear-negative and culture-positive specimens.

We compared the performance of a fluorescence lateral flow assay (ichroma™ IGRA-TB) with the QuantiFERON-TB Gold PLUS (QFT-PLUS) for the diagnosis of latent tuberculosis infection (LTBI) in patients with immune-mediated inflammatory diseases (IMID) prior to receiving biologics therapy.The comparability of the ichroma™ IGRA-TB assay with the QFT-PLUS assay for the diagnosis of LTBI was determined in prospectively enrolled patients with IMID prior to receiving biologics between August 2018 and October 2019. To determine the best cut-off value of the ichroma™ IGRA-TB, an ROC curve analysis was performed.Patients with IMID (n = 145) had inflammatory bowel disease (n = 83; 57.2%), rheumatoid arthritis (n = 44; 30.3%), or spondyloarthropathy (n = 18; 12.4%). The median age was 40.5 (interquartile range: 27.0-56.0), 72 (49.7%) were men, and 140 (96.6%) received BCG vaccination. With the manufacturer-recommended cut-off values, 11 (7.6%) and 20 (13.8%) patients showed positive results with the ichroma™ IGRA-TB and QFT-PLUS tests, respectively. The overall agreement between the two tests was 91.0% with a Cohen's kappa value of 0.535 (95% confidence interval: 0.317-0.754). ROC curve analysis of the QFT-PLUS results showed that a cut-off value of0.21 IU/mL would improve the performance of the ichroma™ IGRA-TB. Using the new cut-off value, the concordance rate was improved to 93.1% with a Cohen's kappa value of 0.668 (95% confidence interval: 0.478-0.858).The ichroma™ IGRA-TB could be used as a point-of-care test for LTBI screening in IMID patients before starting biologics, especially in resource-limited settings. Key Points • The ichroma™ IGRA-TB is an automated fluorescence lateral flow assay-based IGRA. • The test has advantages like short turn-around time, low-cost, and ease of use. • The ichroma™ IGRA-TB showed high agreement with the QuantiFERON-TB Gold In-Tube in patients with chronic immune-mediated inflammatory diseases before starting biologics.

Introduction The temporal dynamics of cavity formation in patients with the noncavitary nodular bronchiectatic (NC-NB) form of Mycobacterium avium complex pulmonary disease (MAC-PD) have not yet been well described. We aimed to investigate the development of new cavities in the NC-NB form of MAC-PD. Methods Of the patients diagnosed with NC-NB-type MAC-PD between 2002 and 2013 and followed-up until July 2018 at a tertiary referral center in South Korea, we identified 589 patients who underwent follow-up chest computed tomography at least once after the diagnosis and retrospectively analysed their medical records. Results The patients’ mean age was 62.0 years, 64.7% were women. During the median follow-up of 3.8 years (interquartile range [IQR] 1.7–5.9), new cavity formation was noted in 51 (8.7%) patients. The median interval between the diagnosis of NC-NB MAC-PD and cavity formation was 3.7 years (IQR 1.8–5.4), with a constant occurrence over time. The Cox regression analysis showed that a history of pulmonary tuberculosis (adjusted hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.06–3.23; P = 0.030) and M. intracellulare as the causative organism (adjusted HR 2.03; 95% CI 1.15–3.59; P = 0.014) were independently associated with new cavity formation. Conclusions New cavity formation was noted in 8.7% of the patients with NC-NB MAC-PD in approximately 4 years after diagnosis, particular in those infected with M. intracellulare and those with a previous history of tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB), a major global health concern, requires long-term treatment with multiple drugs, which can cause many side effects [1]. Therefore, an effective regimen with a minimum number of drugs is essential to control this disease. Bedaquiline (Bdq) and delamanid (Dlm) are new drugs that exhibit good efficacy and safety for MDR-TB treatment [1]. However, adding only one of the new drugs to a regimen may be insufficient to cure this disease when the infecting strain has a high level of drug resistance, such as fluoroquinolone-resistant MDR-TB or extensively drug-resistant TB (XDR-TB) [1–3]. Therefore, the concurrent use of Bdq and Dlm can effectively strengthen the treatment regimen if the best practices in “off-label” use are followed [4–10]. This study analysed the efficacy and safety of concurrent use of Bdq and Dlm in patients with MDR-TB and XDR-TB treated under a programmatic condition. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;. Conflict of interest: Dr. Kwon has nothing to disclose. Conflict of interest: Dr. Jeon has nothing to disclose. Conflict of interest: Dr. Kang has nothing to disclose. Conflict of interest: Dr. Yim reports and I received donations of linezolid (Zyvox) from Pfizer Inc. and Delamanid (Deltyba) from Otsuka Pharmaceutical Co. for the clinical trials which I serve(d) as a principal investigator.. Conflict of interest: Dr. SHIM has nothing to disclose.

Objectives The objective of this study was to evaluate the efficacy and safety of the sequential use of bedaquiline (Bdq) and delamanid (Dlm) in patients with multidrug-resistant tuberculosis (MDR-TB) and limited treatment options. Methods This study evaluated 74 MDR-TB patients treated between March 2016 and December 2018 with Bdq followed by Dlm (n = 22), or vice versa (n= 52), combined with optimized background regimens. Results The mean age of the participants was 49.0 ± 15.8 years. Fifty-one (68.9%) of the participants were male. Fluoroquinolone resistance was identified in 54 (72.9%) patients, including 20 (27.0%) with extensively drug-resistant TB. Of the 47 (63.5%) patients with positive cultures at the commencement of the first new drug, culture conversion occurred in 44 (93.6%). The interim treatment outcome after 12 months was favourable in 68/74 patients (91.9%). Twenty-four weeks of treatment were completed in 137 of 148 episodes of new drug use (92.3%). Regarding the 11 early discontinuation events, six patients stopped using a new drug due to adverse drug reactions that were not life-threatening, including one (1.4%) who stopped Bdq due to QT-prolongation. Conclusions Sequential use of the two new drugs appears to be an effective and safe option for MDR-TB patients with few treatment options.

Background The purpose of this study was to evaluate the current status and trends in the coverage of molecular drug susceptibility testing (mDST), and the impact of mDST on the time to multidrug-resistant tuberculosis (MDR-TB) treatment initiation in Korea. Methods We included confirmed rifampin-resistant (RR)/MDR-TB patients who submitted application forms for novel drug uses to the National TB Expert Review Committee from September 1, 2016 to November 30, 2019. We retrospectively reviewed their medical records. Results Of the 621 MDR/RR-TB patients, mDST was performed in 442 (71.2%); Xpert MTB/RIF (Xpert) alone in 109 (17.6%), MTBDRplus line probe assay (LPA) alone in 199 (32.0%), and both Xpert and LPA in 134 (21.6%) patients. The coverage rate of mDST has gradually increased to 70% in 2015, 50.7% in 2016, 67.9% in 2017, 75.2% in 2018, and 79.4% in 2019 (P for trend < 0.001). Median time to MDR-TB treatment initiation was 35 days (interquartile range25–75 0–72), which has gradually decreased during the study period (P < 0.001). Independent predictors of shorter time to MDR-TB treatment initiation were retreatment case (adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 1.10–1.54), Xpert testing (aHR, 2.42; 95% CI, 2.03–2.88), and LPA testing (aHR, 1.83; 95% CI, 1.55–2.16). Transfer to another healthcare facility was inversely related to shorter time to treatment initiation (aHR, 0.74; 95% CI, 0.63–0.88). Conclusion mDST coverage is gradually increasing and contributes to reducing the time to MDR-TB treatment initiation. Further efforts are needed to achieve universal access to mDST and to properly integrate mDST into routine clinical practice., Graphical Abstract

Purpose Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. Materials and methods This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. Results Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). Conclusion Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12–99) with positive IGRA results.

Mutations in the rpoB gene of Mycobacterium tuberculosis can result in resistance to rifampin. Among various mutations in the rpoB gene, some known as disputed rpoB mutations can cause low-level rifampin resistance. It has been suggested that a high-dose rifampin (20 mg/kg)-based regimen might be effective in treating tuberculosis (TB) caused by M. tuberculosis with disputed rpoB mutations exhibiting low-level resistance. We herein report the first two cases of pulmonary TB caused by M. tuberculosis with a disputed rpoB mutation (CTG511CCG) that showed successful treatment outcomes with a high-dose rifampin-based regimen.

Background Lung transplantation (LTPL) is considered as a salvage therapeutic option in patients with end-stage lung disease. However, there is a lack of sufficient data on the use of LTPL in patients with acute respiratory distress syndrome (ARDS). Although there are few case reports on lung transplant for ARDS, no case series exists up to date. The aim of this study was to evaluate the clinical outcomes of patients with ARDS in accordance with the LTPL status. Methods Patients who had severe ARDS (PaO2/FiO2 ratio ≤ 100 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O) and were listed for LTPL with no underlying end-stage lung disease were included in this single-center retrospective study. Demographic and clinical data of the patients were collected and analyzed. Results Fourteen patients were listed for LTPL due to severe ARDS. All patients received mechanical ventilation, and 12 (86%) patients underwent extracorporeal membrane oxygenation. Of the 9 patients who underwent LTPL, 8 (89%) survived, whereas only 1 (20%) patient out of those who did not receive LTPL survived. The median survival time of the patients who underwent LTPL was 1996 days (interquartile range [IQR], 872-2239), compared with 49 days (IQR, 872-2239) in patients who did not undergo LTPL. The median survival time after LTPL was 64 months (IQR, 28-72). The 3-year survival rate of the recipients was 78%. Conclusions LTPL may be considered as a therapeutic option in a select group of patients with severe ARDS. However, the irreversibility of the patient's lung status should be considered.

Background The incidence of nontuberculous mycobacterial (NTM) infection has increased over the last 10 years. However, the clinical characteristics and treatment outcomes of patients with NTM pleuritis have not been well defined. Methods Patients with pleural effusion and NTM lung disease diagnosed between 1997 and 2013 were enrolled and their medical records were reviewed retrospectively. The subjects were divided into definite (n = 9, NTM isolated from the pleura or pleural effusion) and possible (n = 5, NTM lung disease with pleural effusion and improvement of effusion after anti-NTM treatment) groups. Clinical characteristics and treatment outcomes were analyzed. Patients with Mycobacterium avium complex (MAC) lung disease but without pleuritis were selected (the MAC-LD group) and compared with the MAC pleuritis (MAC-PD) group. Results The median age of the 14 NTM pleuritis patients was 68 years, and the majority were men (9/14, 64.3%). Mycobacterium intracellulare was the most common species detected (50.0%), followed by M. avium (35.7%), M. abscessus (7.1%) and M. kansasii (7.1%). The median lymphocyte frequency and adenosine deaminase level in the effusion were 83% and 97 IU/L, respectively. Eight patients successfully completed treatment, although 2 patients died as a consequence of uncontrolled NTM disease. The MAC-PD group had less nodular bronchiectatic lung features and a lower treatment success rate than the MAC-LD group. Conclusion The laboratory characteristics of pleural effusions from patients with NTM disease were similar to those of patients with tuberculous pleuritis. The treatment outcome of MAC-PD appears to be worse than that of MAC-LD. Therefore, clinicians need to be alert to successfully manage patients with MAC-PD.

Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases.In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed.Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (Funded by Insmed; WILLOW ClinicalTrials.gov number, NCT03218917.).

Background Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB. Methods Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation. Results The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045). Conclusion These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.

Sir,In the present journal, an evaluation of Cobas TaqMan MTB test for the detection of Mycobacterium tuberculosis complex on various clinical specimens was presented [1]. Based on culture as refer...

Purpose The Korea Centers for Disease Control & Prevention has implemented a review process for the approval of new drugs used to treat patients with multidrug-resistant tuberculosis (MDR-TB) since September 2016. Therefore, this study aimed to evaluate the efficacy and safety of these new drugs bedaquiline (Bdq) and delamanid (Dlm). Methods A total of 318 patients with MDR-TB were reviewed by the committee from September 2016 to February 2018; 282 (88.7%) of them were treated with the new drugs (Bdq, 107 patients; Dlm, 108 patients; and both concurrently or sequentially, 67 patients) and retrospectively evaluated. Culture conversion rates, interim treatment outcomes at 12 months, and predictors of unfavorable outcomes were analyzed. Treatment efficacy was also compared between Bdq and Dlm. Results The mean age of the patients was 49.3 years, and 197 (69.9%) were male. Three patients were HIV seropositive and 151 (53.5%) were quinolone resistant. The culture conversion rates at 2 and 6 months were 57.4% (81/141) and 89.4% (126/141), respectively. A favorable outcome at 12 months was achieved in 84.8% of patients (239/282). Differences in the culture conversion rate or interim treatment outcomes were not statistically significant among the drug susceptibility test patterns or new drugs used. Multivariable analysis showed that age >60 years and body mass index of Conclusions The use of new drugs resulted in satisfactory interim treatment results, without significant differences between them.

No studies have investigated whether the discontinuation of ethambutol (EMB) based on susceptibility to isoniazid and rifampin, as determined by the GenoType MTBDRplus assay, would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of the intensive phase of treatment based on the results of the MTBDRplus assay in patients with pulmonary tuberculosis (PTB). This prospective, multicenter noninferiority randomized trial was conducted at 12 referral centers in South Korea in drug-susceptible PTB patients who initiated the standard four-drug regimen for PTB. Based on the results of the assay, EMB was discontinued in the MTBDRplus group after confirmation that the M. tuberculosis isolate was susceptible to isoniazid and rifampin. The time point for EMB discontinuation in the guideline group was determined using the results of the phenotypic drug susceptibility test based on the South Korean national tuberculosis guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Of 600 randomized patients, the treatment outcome analysis was performed for 493 patients (MTBDRplus group, 244 patients; guideline group, 249 patients). Treatment success rates were 93.9% (229/244) in the MTBDRplus group and 93.6% (233/249) in the guideline group and did not differ between groups (relative risk, 1.00; 95% confidence interval, 0.95 to 1.06). The 1-year recurrence rates in the two groups (0.9% and 0.5%, respectively) and adverse drug reactions did not differ between the groups. In conclusion, the early discontinuation of EMB based on the results of the MTBDRplus assay did not affect the treatment outcomes in patients with PTB. (This clinical trial has been registered with the Clinical Research Information Service of the Republic of Korea [https://cris.nih.go.kr/cris/] under registration no. KCT0000610.)

Background: Hemoptysis is one of the most important complications associated with fungus ball. However, the association of the primary size of the fungus ball and its change with the incidence of hemoptysis was not fully established. This study aims to determine the clinical risk factors of severe hemoptysis and natural course of fungus ball. Methods: A retrospective study on patients with fungus ball was performed. Patients with severe hemoptysis-related events were compared to those without events, and the predictors for severe hemoptysis were investigated by Cox regression analysis. Three subgroups (decreased, stable, and increased) were classified according to the long-term size change, and the severe hemoptysis-free survival duration was analyzed by the Kaplan-Meier survival curve. Results: Among 173 patients, 50 (28.9%) experienced severe hemoptysis-related events. Risk-adjusted analysis revealed that age [hazard ratio (HR), 0.964; 95% confidence interval (CI), 0.939–0.989], blood-tinged sputum [HR, 2.717; 95% CI, 1.513–4.879], and thick wall cavitary fungus balls [HR, 2.332; 95% CI, 1.290–4.215] were significant predictors of severe hemoptysis-related events in patients with fungus ball. However, the baseline size of the fungus ball and its change rate were not independent risk factors for severe hemoptysis-related events. Besides, the decreased group did not have a favorable outcome in severe hemoptysis related to fungus ball. Conclusions: In a tertiary hospital, the incidence of severe hemoptysis-related events in patients with fungus ball was not low and reached 28.9%. Young patients, those with thick wall cavitary fungus ball, and those with complaints of blood-tinged sputum should be considered for early surgical treatment to prevent severe hemoptysis.

Although treatment success for multidrug-resistant tuberculosis (MDR-TB) in Korea has increased owing to a national TB program and insurance coverage, Korea still has the highest TB incidence and associated mortality among the OECD Countries. Further, the final treatment outcome with bedaquiline in Korea has not been evaluated. In the present study, we compared the safety and efficacy of bedaquiline in Korean population, with advanced resistant profile, with those of the total population of the C209 trial to obtain valuable information. In the C209 trial, patients with MDR-TB received bedaquiline for 24 weeks in combination with optimized background regimen and all patients were followed up for 96 weeks after the last administration of bedaquiline. A subgroup analysis was performed in 21 Korean patients enrolled in the C209 trial. The baseline characteristics were similar between the two groups, except the drug-susceptibility pattern. The proportion of patients with pre-extensively drug resistant (XDR)/XDR-TB was 61.9% and 35.2% in the Korean population and total C209 population, respectively. Aminoglycosides, later generation fluoroquinolones, cycloserine, and linezolid were the most frequent drugs concomitantly used during bedaquiline treatment. The culture conversion rate was similar at the end of bedaquiline treatment (80% vs. 79.5%) and at 120 weeks (75% vs. 72.2%). The frequency and type of adverse events were similar between the two groups. In conclusion, bedaquiline showed similar efficacy and safety in Korean patients with MDR-TB despite their advanced drug-resistant profile, likely due to the effective companion drugs such as linezolid and later generation fluoroquinolones.

Background: Clarithromycin (CLR) and azithromycin (AZM) are the cornerstones in the treatment of Mycobacterium avium complex lung disease (MAC-LD). It has been recommended that either drug can be used without preference because no data are available to suggest the superiority of CLR or AZM. Aims: To compare CLR and AZM in terms of severe adverse event (SAE) rate and treatment outcomes in MAC-LD patients Methods: Among the patients diagnosed with MAC-LD in 2001–2013, 560 who received at least one dose of the standard regimen until May 2018 were selected for the adverse events analysis. Of them, 316 patients who underwent standard treatment for ≥12 months were selected for the treatment outcome analysis. The medical records were retrospectively analyzed. Results: Among the 560 patients, 466 (83.2%) and 94 (16.8%) were started on CLR and AZM containing regimen, respectively. The SAE rate, which led to permanent drug discontinuation, was significantly higher in CLR than in AZM (24.2% vs 9.6%, P=0.002). The overall treatment success rate of the 316 patients who received the standard regimen for ≥12 months was 83.2%. No difference of treatment success rate was observed between the CLR and AZM containing regimens (82.9% vs 84.3%, P=0.788). The one- and three-year recurrence rates were similar for the two drugs (6.8% vs 6.0%, P>0.999 and 31.0% vs 37.5%, P=0.482). Conclusions: These findings suggest that AZM containing regimen may be the better initial choice for the treatment of MAC-LD as it results in lesser SAE while offering similar patient outcomes when compared with the CLR containing regimen.

Purpose We investigated the adverse events (AEs) and treatment completion rates of a 3 month course of once-weekly isoniazid and rifapentine (3H1P1) in South Korean health care workers (HCWs) with latent tuberculosis infection (LTBI). Methods HCWs who were candidates for LTBI treatment were enrolled from two tertiary referral centers between December 2016 and October 2017. From December 2016 through March 2017, HCWs who agreed were treated with the 3H1P1 regimen (3H1P1 group). Their compliance and AEs were prospectively collected. From April 2017 onward, HCWs who required LTBI treatment received 3 months of isoniazid plus rifampin (3HR group), and their medical records were retrospectively reviewed. Results During the study period, 406 HCWs were treated, 226 (55.7%) in the 3H1P1 group, and 180 (44.3%) in the 3HR group. The number of subjects with AEs was significantly greater in the 3H1P1 group (75.2% vs 56.7%, P Conclusions The 3H1P1 regimen had a higher treatment completion rate and lower hepatotoxicity compared with the 3HR regimen. However, it resulted in a higher rate of flu-like syndromes. Additionally, a few subjects had anaphylaxis, although there were no fatalities.

Rapid detection of drug-resistant tuberculosis (DR-TB) is crucial for timely treatment and management. The GenoType MTBDRplus and MTBDRsl (MTBDR) assays have been endorsed by the World Health Organization (WHO) for the detection of DR-TB. However, MTBDR assays cannot simultaneously detect multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Furthermore, interpretation of the MTBDR assay requires trained people, and the assay has low sample throughput, processing only up to 12 samples in parallel. We have developed the Quantamatrix Multiplexed Assay Platform (QMAP) to detect MDR-/XDR-TB simultaneously. The interpretation of QMAP results is automated, and the platform can process up to 96 samples in parallel. To compare the performance of QMAP with MTBDR assays, we performed QMAP and the MTBDR assay on 76 smear-positive, Mycobacterium tuberculosis culture-positive sputum specimens. Compared with phenotypic drug susceptibility testing (DST) results, the sensitivity and specificity of QMAP were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 100% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of MTBDR assays were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 98.1% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of QMAP were 85.0 and 100%, respectively, for the detection of MDR-TB and 100 and 100%, respectively, for XDR-TB. The sensitivity and specificity of MTBDR assays was consistent with those of QMAP. Our study showed that the QMAP assay has sensitivity and specificity equivalent to that of MTBDR assays in smear-positive sputum specimens. In combination with phenotypic DST, QMAP might be useful as a supplementary DST assay for rapid detection of MDR-/XDR-TB.

Background The final treatment outcomes of Korean multidrug-resistant tuberculosis (MDR-TB) patients treated with bedaquiline in the C209 trial have not yet been reported. Therefore, a subgroup analysis of the Korean population from the C209 trial was performed, and the results were compared with those of the overall C209 study population. Methods In the C209 trial, MDR-TB patients were treated with bedaquiline for 24 weeks in combination with background anti-TB drugs, and were followed-up until week 120 after bedaquiline treatment initiation. Results With the exception of drug susceptibility patterns, the baseline clinical characteristics of both groups were similar. The proportions of pre-extensively drug-resistant TB to extensively drug-resistant TB (pre-XDR-TB/XDR-TB) were 61.9 and 35.2% in the Korean and the overall C209 populations, respectively. Aminoglycosides, later-generation fluoroquinolones, cycloserine, and linezolid were the most common concomitant drugs used during bedaquiline treatment. The culture conversion rates of both groups were similar at week 24 (end of bedaquiline treatment; 80.0% vs. 79.5%) and 120 (75.0% vs. 72.2%). Additionally, the frequency and type of adverse events during treatment were similar in both groups, and 1 patient (5.0%) died due to a cause unrelated to bedaquiline treatment. Conclusions Bedaquiline showed similar efficacy and safety in Korean patients with MDR-TB, despite their advanced drug-resistance profiles, possibly due to other concomitant drugs such as linezolid.

Background Recently, the number of lung transplants in South Korea has increased. However, the long-term outcome data is limited. In this study, we aimed to investigate the long-term outcomes of adult lung transplantation recipients. Methods Among the patients that underwent lung transplantation at a tertiary referral center in South Korea between 2008 and 2017, adults patient who underwent deceased-donor lung transplantation with available follow-up data were enrolled. Their medical records were retrospectively reviewed. Results Through eligibility screening, we identified 60 adult patients that underwent lung (n=51) or heart-lung transplantation (n=9) during the observation period. Idiopathic pulmonary fibrosis (46.7%, 28/60) was the most frequent cause of lung transplantation. For all the 60 patients, the median follow-up duration for post-transplantation was 2.6 years (range, 0.01-7.6). During the post-transplantation follow-up period, 19 patients (31.7%) died at a median duration of 194 days. The survival rates were 75.5%, 67.6%, and 61.8% at 1 year, 3 years, and 5 years, respectively. Out of the 60 patients, 8 (13.3%) were diagnosed with chronic lung allograft dysfunction (CLAD), after a mean duration of 3.3±2.8 years post-transplantation. The CLAD development rate was 0%, 17.7%, and 25.8% at 1 year, 3 years, and 5 years, respectively. The most common newly developed post-transplantation comorbidity was the chronic kidney disease (CKD; 54.0%), followed by diabetes mellitus (25.9%). Conclusion Among the adult lung transplantation recipients at a South Korea tertiary referral center, the long-term survival rates were favorable. The proportion of patients who developed CLAD was not substantial. CKD was the most common post-transplantation comorbidity.

Background We investigated discrepant results determined using the Genotype®MTBDRplus assay and a conventional antimicrobial drug susceptibility test (ADST) for isoniazid (INH) resistance using sequencing analysis and analyzed the clinical course of patients with discrepant results. Methods Among 1373 MTBDRplus assays performed at our tertiary referral center in South Korea between August 2009 and December 2015, the results for 46 (3.4%) differed from those for ADST. KatG and inhA gene sequencing analysis results were available for 23 patients. ADSTs were carried out using the absolute concentration method with Lowenstein–Jensen media. Results Results from 11 patients indicated INH susceptibility by MTBDRplus assay and INH resistance by ADST. For 5 of these patients, sequencing revealed no evidence of mutations, whereas specific mutations were detected in the remaining 6 patients. These should have been detected using the MTBDRplus assay. The other 12 patients had isolates with the opposite discrepancy, that is INH resistance by MTBDRplus assay but INH susceptibility by ADST. For 7 of these cases, sequencing results were consistent with those of the MTBDRplus assay. However, sequencing analysis did not explain the discrepancies in the remaining 5 patients. All 23 patients with discrepant results received individualized treatment regimens determined by the attending physician according to their test results and susceptibility to other drugs, such as rifampin. Good outcomes were reported for the majority. Conclusion Discrepancies between test results for INH resistance on the MTBDRplus assay and ADST appear to be infrequent. Gene sequencing analysis is useful for identifying the cause of the discrepancy.

Background We investigated the effects of corticosteroids on the 90-day mortality outcomes in patients with pulmonary tuberculosis who were admitted to the intensive care unit (ICU) because of acute respiratory failure (ARF). Methods The medical records of 124 patients who had pulmonary tuberculosis with ARF and were admitted to the ICU at our tertiary referral center in South Korea between March 1989 and December 2014 were retrospectively analyzed. The 90-day mortality rate in this population was analyzed after adjustments with the inverse probability of treatment weighted (IPTW) method. Results The mean patient age was 62 years, and the 90-day mortality rate was 49.2% (61/124). Adjuvant steroids were used in 70 (56.5%) patients. The 90-day mortality rate was similar irrespective of corticosteroid use (48.6%, steroid group; 50.0%, nonsteroid group). The use of adjuvant steroids was not associated with the unadjusted 90-day mortality (odds ratio [OR], 0.94; 95% confidence interval [CI], .46-1.92; P = .875). In a comparison using an adjusted IPTW approach of the 90-day mortality between the 2 groups, we found that corticosteroid use was independently associated with reduced 90-day mortality (OR, 0.47; 95% CI, .22-.98; P = .049). Conclusions The study results showed that corticosteroids could reduce the 90-day mortality rate in critically ill pulmonary tuberculosis patients with ARF.

We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment.To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin.A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups.Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001).The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

Background/Aims Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. Methods We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. Results Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. Conclusions In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.

Background Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) remain unsatisfactory, and long-term use of second-line anti-TB drugs is accompanied by the frequent occurrence of adverse events, low treatment compliance, and high costs. The development of new efficient regimens with shorter treatment durations for MDR-TB will solve these issues and improve treatment outcomes. Methods This study is a phase II/III, multicenter, randomized, open-label clinical trial of non-inferiority design comparing a new regimen to the World Health Organization-endorsed conventional regimen for fluoroquinolone-sensitive MDR-TB. The control arm uses a conventional treatment regimen with second-line drugs including injectables for 20–24 months. The investigational arm uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence of adverse events grade 3 and above as evaluated by the Common Terminology Criteria for Adverse Events. Based on an α = 0.025 level of significance (one-sided test), a power of 80%, and a

Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.