Management of newborns and healthcare workers exposed to isoniazid-resistant congenital tuberculosis in the neonatal intensive care unit.

BACKGROUND: Management of newborns and healthcare workers (HCWs) exposed to congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) has been reported rarely. AIM: To outline a contact investigation process for individuals exposed to congenital TB in the NICU and investigate nosocomial transmission. Additionally, to assess the efficacy and safety of window prophylaxis in exposed newborns. METHODS: A baby, born at a gestational age of 28 + 1 weeks, was diagnosed with isoniazid-resistant congenital TB on the 39th day of admission to the level IV NICU. Newborns and HCWs exposed cumulatively for ≥8 h underwent contact investigation and follow-up for a year. FINDINGS: Eighty-two newborns underwent contact investigation. All newborns displayed normal chest X-rays, and 42 hospitalized newborns tested negative for acid-fast bacilli stain and Xpert® MTB/RIF assay in their endotracheal sputum or gastric juices. Eighty received window prophylaxis: six of 75 on rifampin experienced mild adverse events, and none of the five on levofloxacin. After 12 weeks, five (6.1%) had a positive tuberculin skin test, all of whom had already received the Bacillus Calmette-Guérin vaccine and tested negative on TB interferon-gamma releasing assay. Of 119 exposed HCWs, three (2.5%) were diagnosed with latent TB infection and completed a four-month rifampin therapy. There was no active TB disease among exposed newborns and HCWs during a one-year follow-up. CONCLUSION: Timely diagnosis of congenital TB is crucial for minimizing transmission among exposed neonates and HCWs in the NICU setting. In cases of isoniazid-resistant index patients, even premature newborns may consider the use of rifampin or levofloxacin for window prophylaxis.

Compliance with new drug use and the effect of discrepant drug susceptibility testing on MDR/RR-TB treatment.

BACKGROUND: Following the WHO???s announcement in 2018, the use of new drugs was recommended for all patients with multidrug-resistant TB (MDR-TB) in Korea. This study aimed to evaluate adherence to new anti-TB drug regimens and implementation of molecular drug susceptibility testing (mDST) in Korea.METHODS: Nationwide, 560 patients were reported as having MDR-TB in 2021. The implementation of mDST and new anti-TB drug use were analysed. The discrepancy between mDST and phenotypic DST (pDST) results and their implications on the use of new anti-TB drugs were also analysed. The use of novel anti-TB drugs has been approved by the National TB Expert Committee.RESULTS: The non-adherence rate in MDR-TB patients was 14.3%. The mDST implementation rate was 96.1%. Of the 459 patients who underwent both mDST and pDST, the discordance rate for rifampicin (RIF) resistance was 22.6% (n = 104), of which 72.1% (n = 75) were resistant on mDST but susceptible on pDST. The discrepancy in mDST and pDST results related to RIF resistance was found to be the main cause of non-adherence to new drug regimen.CONCLUSION: Comprehensive training on how to interpret conflicting results between mDST and pDST could enhance the utilisation of new drugs in the treatment of MDR/RIF-resistant TB.

Treatment outcome, recurrence and safety of multidrug-resistant TB treated with low-dose linezolid.

BACKGROUND: Linezolid (LZD) is a key treatment option for patients with multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We investigated the long-term treatment outcomes and safety of MDR/RR-TB treatment using low-dose LZD.METHODS: Medical records of patients with MDR/RR-TB treated with LZD ≥4 weeks between 2004 and 2018 at the Asan Medical Center, Seoul, Republic of Korea, were reviewed. Standard-dose and low-dose LZD groups were defined as patients initially administered LZD ≥600 mg/day or 300 mg/day, respectively.RESULTS: Among 94 patients, 65 were included in the low-dose LZD group; mean age was 43.1 ± 15.6 years, 53 (56.4%) were men and 77 (83.7%) were resistant to fluoroquinolone. The low-dose LZD group showed features of less severe disease, such as limited MDR-TB history and less severe radiological findings. There was no difference in treatment outcomes, relapse and safety between groups. In the low-dose LZD group, 54 (83.1%) succeeded treatment, of whom 48 (88.9%) were followed-up for a median of 38 months; there was no recurrence. Adverse drug reactions were reported in 41 (63.1%); peripheral neuropathy was most frequently reported (n = 31, 47.7%), while myelosuppression was reported in 12 (18.5%).CONCLUSION: Low-dose LZD in selected patients with less severe disease is both effective in the long-term and safe for the treatment of MDR/RR-TB.

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility.

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

First Report of the Korean Lung Transplantation Registry.

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.

Clinical significance of QT-prolonging drug use in patients with MDR-TB or NTM disease.

SETTING: Many drugs with potential QT prolongation effects (QT drugs) have already been used for decades in patients with multidrug-resistant TB (MDR-TB) or non-tuberculous mycobacterial (NTM) disease, but without a common consensus. OBJECTIVE: To investigate the effects of QT drugs on cardiac events in patients with MDR-TB or NTM disease. METHODS: We retrospectively reviewed 373 patients (mean age: 56.4 years) with MDR-TB or NTM disease treated for >1 month with clofazimine (CFZ), moxifloxacin (MFX), bedaquiline (BDQ), delamanid (DLM) or macrolides (clarithromycin or azithromycin). Adverse cardiac events, death and QTcF changes were evaluated. RESULTS: Forty-four per cent had MDR-TB; 165 (44%), 315 (85%), 10 (3%), 229 (61%) and 1 patient received CFZ, MFX, BDQ, macrolides and DLM, respectively. Except for three patients (0.8%) lost to follow-up with unknown cause of death, 3 (0.8%, 95%CI 0.2-2.4) adverse cardiac events were documented: atrial fibrillation, cardiac tamponade due to TB pericarditis and cardiac arrest, which was determined to not have been caused by QT drugs. Clinically significant QTcF changes (QTcF > 500 msec or an increase > 60 msec) were observed in 10/60 patients (17%, 95%CI 8.0-30.7) without clinical events. CONCLUSION: The use of QT drugs, alone or in combination, in the treatment of MDR-TB or NTM disease is relatively safe.

Comparison of LTBI treatment regimens for patients receiving anti-tumour necrosis factor therapy.

SETTING: A tertiary referral centre in South Korea. OBJECTIVE: To compare the completion rates and adverse drug reactions of three latent tuberculous infection (LTBI) treatment regimens for patients receiving anti-tumour necrosis factor (anti-TNF) therapy. DESIGN: A total of 408 patients were diagnosed with LTBI before receiving anti-TNF therapy between December 2004 and December 2013. Nine months of isoniazid (9H), 4 months of rifampicin (4H) or 3 months of isoniazid/rifampicin (3HR) were prescribed. The results were analysed retrospectively. RESULTS: The mean age of the 408 study subjects was 44 years; 258 (63.2%) were male. The 9H, 4R and 3HR treatment regimens were given to respectively 61 (15.0%), 139 (34.1%) and 208 (51.0%) patients. A total of 362 (88.7%) patients completed the treatment. The treatment completion rate was highest in patients receiving 3HR (94.2%). Of the 408 patients, 54 (13.2%) had one or more adverse drug reactions; their frequency was similar in the three groups. CONCLUSIONS: In patients receiving anti-TNF therapy, 3HR seems to be the most acceptable treatment regimen for LTBI, given its high completion rate and acceptable rate of adverse drug reactions.

The 'either test positive' strategy for latent tuberculous infection before anti-tumour necrosis factor treatment.

SETTING: A ttertiary referral centre in South Korea. OBJECTIVES: The 'either test positive' strategy, incorporating both the tuberculin skin test (TST) and the T-SPOT(®).TB(T-SPOT) assay, was evaluated as a novel method for diagnosing latent tuberculous infection (LTBI) before treatment with anti-tumour necrosis factor (TNF) in patients with immune-mediated inflammatory diseases. DESIGN: From June 2008 to April 2012, 430 patients received anti-TNF treatment at our institution. TST and T-SPOT were performed simultaneously at baseline. LTBI was defined as a positive TST or a positive T-SPOT result. RESULTS: The positivity rates for the TST and T-SPOT assays were respectively 19.1% (82/430) and 44.2% (190/430), yielding an LTBI-positive rate of 48.6% (209/430). LTBI treatment was initiated in 46.0% (198/430) of patients and was completed by 89.4% (177/198). During follow-up (median 884 days), 0.9% (4/430) of the patients developed active tuberculosis (TB). All four TB patients were TST-negative at baseline, although two received LTBI treatment based on the baseline positive T-SPOT assay results. CONCLUSIONS: The either test positive strategy is a valid method for diagnosing LTBI before anti-TNF treatment, although it is not clear whether it is superior to other strategies.

Treatment outcomes and moxifloxacin susceptibility in ofloxacin-resistant multidrug-resistant tuberculosis.

SETTING: A tertiary referral centre in Seoul, South Korea. OBJECTIVE: To investigate the effect of moxifloxacin (MFX) susceptibility and later-generation fluoroquinolone (FQ) use on the treatment outcomes of ofloxacin (OFX) resistant multidrug-resistant tuberculosis (MDR-TB). DESIGN: Of 223 patients diagnosed with MDR-TB between January 2006 and December 2012, 70 (31.4%) patients with OFX-resistant MDR-TB were enrolled in this retrospective cohort study. Their treatment outcomes were analysed. RESULTS: The mean age (standard deviation) of the 70 patients was 40.6 (12.9) years; 43 (61.4%) were male and 26 (37.1%) had extensively drug-resistant TB. Of the 70 patients, 22 (31.4%) had MFX-susceptible TB, while the remaining 48 (68.6%) were MFX-resistant. The MFX-susceptible and -resistant groups were comparable in terms of baseline characteristics (including age, sex and radiological severity), and respectively 90.9% (20/22) and 70.8% (34/48) were treated with later-generation FQ-containing regimens (P = 0.074; mainly MFX [40/54, 74.1%]). Treatment success was achieved in 72.7% (16/22) of the MFX-susceptible patients and in 41.7% (20/48) of the MFX-resistant patients (P = 0.021). Treatment failure was significantly higher in the MFX-resistant group (41.7% [20/48] vs. 9.1% [2/22]; P = 0.006). CONCLUSION: Patients with OFX-resistant MDR-TB had significantly better treatment outcomes when susceptible to MFX. This probably reflects the effect of later-generation FQ treatment.

Systematic review and meta-analysis of prophylactic antibiotics in COPD and/or chronic bronchitis.

BACKGROUND: Exacerbations contribute substantially to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To assess whether prophylactic antibiotic treatment reduces exacerbations in patients with COPD and/or chronic bronchitis. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, Koreamed and references from relevant publications were searched up to October 2011. Randomised controlled trials comparing the effect of any prophylactic antibiotics with placebo for at least 3 months were included. The co-primary outcomes were the frequency of exacerbations of COPD or chronic bronchitis and adverse treatment events. RESULTS: A total of 19 trials involving 3932 subjects were included in the analysis: 5 recent trials included patients with moderate to severe COPD, whereas 14 older trials included patients with chronic bronchitis. The use of antibiotics significantly reduced the rate of COPD exacerbations (risk ratio [RR] 0.73, 95%CI 0.66-0.82), the number of chronic bronchitis exacerbations (standardised mean difference -0.23, 95%CI -0.35--0.11) and the proportion of patients with exacerbations of chronic bronchitis (RR 0.93, 95%CI 0.87-0.99). CONCLUSION: Prophylactic antibiotic treatment has a significant effect in reducing exacerbations in patients with COPD and/or chronic bronchitis.

Three phenotypes of obstructive lung disease in the elderly.

SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To classify the phenotypes in elderly subjects with obstructive lung disease (OLD). METHODS: We analysed 191 subjects aged ≥ 60 years with chronic respiratory symptoms and either obstructive spirometry or bronchial hyperresponsiveness. Factor analysis was performed using commonly measured variables and revealed four significant variables: 1) the ratio of inspiratory capacity to total lung capacity, 2) the total score on the St George's Respiratory Questionnaire, 3) the volume fraction of the lung less than 950 Hounsfield Unit at full inspiration on volumetric computed tomography and 4) post-bronchodilator forced expiratory volume in 1 second (FEV(1)) changes. We performed a cluster analysis on these four variables. RESULTS: The mean age was 68.5 (± 5.2 SD) years and the mean post-bronchodilator FEV(1) was 52.4% (± 16.5) predicted. Three clusters with the following phenotypes were identified: Cluster 1 included subjects with moderate to severe airflow obstruction and bronchodilator reversibility; Cluster 2 subjects had moderate airflow obstruction without bronchodilator reversibility, and Cluster 3 subjects had severe airflow obstruction without bronchodilator reversibility. CONCLUSIONS: We identified three phenotypes in elderly subjects with OLD. Follow-up studies are needed to explore the clinical significance of each phenotype.

Incidence of tuberculosis among health care workers at a private university hospital in South Korea.

SETTING: A private university hospital in South Korea. OBJECTIVE: To investigate the incidence of tuberculosis (TB) among health care workers (HCWs) employed at a university hospital in South Korea. DESIGN: The occurrence of TB cases among HCWs over a 6-year period (2001-2006) was reviewed. The prevalence of TB was compared with that of the general population using a prevalence ratio (PR) adjusted by age and sex. RESULTS: The study involved 8433 people. TB developed in 61 HCWs (0.72%). The prevalence ratio among all HCWs was 1.05 (95%CI 0.80-1.35). In occupational subgroups, the PRs for doctors, nurses and employees in other departments were respectively 0.58 (95%CI 0.30-1.01), 1.81 (95%CI 1.21-2.59) and 0.95 (95% CI 0.58-1.46). For nurses working in TB-related departments, the relative risk of developing TB was 3.4 times higher (95%CI 1.52-8.25) than for employees in other departments (P=0.005). The PR for nurses working in TB-related department was 5.1 (95%CI 3.23-8.42). CONCLUSION: Among HCWs, nurses working in TB-related departments were at increased risk of developing TB. This suggests that some TB develops via in-hospital infection.