Radiologic Subtypes and Treatment Outcome of Unclassifiable Type Mycobacterium avium Complex Pulmonary Disease

Methods@#Ninety-six patients with unclassifiable type MAC-PD who initiated a macrolidecontaining regimen from 2001 to 2020 were identified at a tertiary referral center in South Korea. Among these 96 patients, 1-year culture conversion rate was analyzed for 48 patients who received standard treatment (three-drug oral-antibiotic combination with or without an injectable agent) for ≥ 1 year. @*Results@#The mean age of the 96 patients was 65.4 ± 10.8 years, and 72.9% of them were male. These patients were classified into four major radiologic subtypes; the most common subtype was the focal cavity subtype (n = 31, 32.3%), followed by the focal mass or nodule (n = 23, 24.0%), consolidation upon emphysema (n = 21, 21.9%), and bronchiolitis (n = 21, 21.9%) subtypes. For the 48 patients who received standard treatment for ≥ 1 year, the overall rate of culture conversion at 1-year was 93.8%. All patients in the focal cavity subtype and focal mass or nodule subtype categories achieved 1-year culture conversion. Additionally, 1-year culture conversion rate was 92.9% in consolidation upon emphysema subtype and 75.0% in bronchiolitis subtype. @*Conclusion@#Unclassifiable type MAC-PD can be radiologically further categorized into four major radiologic subtypes. The treatment outcome of all of these subtypes seems to be favorable.

Bronchoesophageal fistula in a patient with Crohn’s disease receiving anti-tumor necrosis factor therapy

Tuberculosis is an adverse event in patients with Crohn’s disease receiving anti-tumor necrosis factor (TNF) therapy. However, tuberculosis presenting as a bronchoesophageal fistula (BEF) is rare. We report a case of tuberculosis and BEF in a patient with Crohn’s disease who received anti-TNF therapy. A 33-year-old Korean woman developed fever and cough 2 months after initiation of anti-TNF therapy. And the symptoms persisted for 1 months, so she visited the emergency room. Chest computed tomography was performed upon visiting the emergency room, which showed BEF with aspiration pneumonia. Esophagogastroduodenoscopy with biopsy and endobronchial ultrasound with transbronchial needle aspiration confirmed that the cause of BEF was tuberculosis. Anti-tuberculosis medications were administered, and esophageal stent insertion through endoscopy was performed to manage the BEF. However, the patient’s condition did not improve; therefore, fistulectomy with primary closure was performed. After fistulectomy, the anastomosis site healing was delayed due to severe inflammation, a second esophageal stent and gastrostomy tube were inserted. Nine months after the diagnosis, the fistula disappeared without recurrence, and the esophageal stent and gastrostomy tube were removed.

The Risk of Tuberculosis in Patients With Inflammatory Bowel Disease Treated With Vedolizumab or Ustekinumab in Korea

The present study investigated the risk of active tuberculosis in patients with inflammatory bowel disease (IBD) treated with vedolizumab or ustekinumab, in actual clinical settings in a country with an intermediate tuberculosis burden. The medical records of 238 patients with IBD who received vedolizumab or ustekinumab were retrospectively reviewed at a tertiary referral center in South Korea. All patients had ≥ 3 months of follow-up duration and underwent a latent tuberculosis infection screening test before initiation of the administration of these drugs. Of the 238 patients enrolled, 181 had Crohn’s disease, and 57 had ulcerative colitis. During the median 18.7 months of follow-up, active tuberculosis did not develop in any patient treated with vedolizumab or ustekinumab. Therefore, we concluded that the risk of tuberculosis appears to be low in patients with IBD treated with vedolizumab or ustekinumab in South Korea.

Recent Advances in Drug Susceptible Pulmonary Tuberculosis Diagnosis and Treatment / 대한내과학회지

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.

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

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.

Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation

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.

Changes in chest X-ray findings in 1- and 2-month group after treatment initiation forsuspected pulmonary tuberculosis

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, nontuberculousmycobacteria and malignancy were the most common causes of improved and aggravated 1- and 2-month CXR findings, respectively. @*Conclusions@#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.

QuantiFERON-TB Gold PLUS versus QuantiFERON- TB Gold In-Tube test for diagnosing tuberculosis infection

Background/Aims@#QuantiFERON-TB Gold PLUS (QFT-PLUS) was developed as a new version of the interferon-γ (IFN-γ) release assay that contains an extra antigen tube to elicit a CD8+ T-cell response in addition to a CD4+ T-cell response. This study aimed to evaluate the performances of QFT-PLUS versus QuantiFERON-TB Gold In-Tube (QFT-GIT) for detecting tuberculosis (TB) infection. @*Methods@#Between October, 2016 and May, 2018, 137 participants were prospectively recruited and subjected to QFT-GIT and QFT-PLUS testing. The concordance between tests and performance based on different immune states and/or TB infection risk were evaluated. @*Results@#The 137 participants were classified as follows: active TB (n = 14), TB contact (n = 14), screening before biologic therapy (n = 85) and other disease (n = 24). The positive results for either test were 100% (n = 14/14), 42.9% (n = 6/14), 15.3% (n = 13/85), and 62.5% (n = 15/24) in each four groups, respectively. The QFT-GIT and QFT-PLUS test results showed good concordance with 91.2% agreement and a Cohen’s κ of 0.807. The good concordance between two tests was also observed in 64 immunocompromised subjects (agreement of 90.6% and a Cohen’s κ of 0.711). The intra-class correlation coefficient for each antigen tube of the QFT-PLUS showed a good correlation with the IFN-γ release of the QFT-GIT (TB1 = 0.912, p < 0.001; TB2 = 0.918, p < 0.001). @*Conclusions@#QFT-PLUS showed highly comparable results to those of QFT-GIT for diagnosing TB infection in South Korea as well as in immunocompromised subjects.

Impact of Molecular Drug Susceptibility Testing on the Time to Multidrug-resistant Tuberculosis Treatment Initiation

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 range 25–75 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.

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

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.

Infections in Lung Transplant Recipients during and after Prophylaxis

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.

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

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.

Infections in Lung Transplant Recipients during and after Prophylaxis

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.

Protocol of a Nationwide Observational Study among Patients with Nontuberculous Mycobacterium Pulmonary Disease in South Korea (NTM-KOREA) / 결핵및호흡기질환

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.

Protocol of a Nationwide Observational Study among Patients with Nontuberculous Mycobacterium Pulmonary Disease in South Korea (NTM-KOREA) / 결핵

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.

Correlation between GenoType MTBDRplus Assay and Phenotypic Susceptibility Test for Prothionamide in Patients with Genotypic Isoniazid Resistance / 결핵및호흡기질환

BACKGROUND@#The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto).@*METHODS@#A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay.@*RESULTS@#The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations.@*CONCLUSION@#It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.

Correlation between GenoType MTBDRplus Assay and Phenotypic Susceptibility Test for Prothionamide in Patients with Genotypic Isoniazid Resistance / 결핵

BACKGROUND: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). METHODS: A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay. RESULTS: The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. CONCLUSION: It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.

Characteristics of Lung Allocation and Outcomes of Lung Transplant according to the Korean Urgency Status

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.

Long-Term Outcomes of Adult Lung Transplantation Recipients: A Single-Center Experience in South Korea / 결핵

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.

Concurrent, Prolonged Use of Bedaquiline and Delamanid for Multidrug-Resistant Tuberculosis / 대한내과학회지

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.