Cost-Effectiveness of Age-Expanding Strategy of Latent Tuberculosis Infection Treatment in Household Contacts in South Korea.

PURPOSE: The strategy of latent tuberculosis infection (LTBI) treatment in household tuberculosis (TB) contacts has been expanding in South Korea. However, there is little evidence of the cost-effectiveness of LTBI treatment in patients over 35 years of age. This study aimed to evaluate the cost-effectiveness of LTBI treatment among household TB contacts in different age groups in South Korea. MATERIALS AND METHODS: An age-structured model of TB was developed based on the reports from the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Quality-adjusted life-years (QALY) and the averted number of TB-related deaths were estimated along with discounted costs for a measure of incremental cost-effectiveness ratios. RESULTS: The number of cumulative active TB cases would decrease by 1564 and 7450 under the scenario of LTBI treatment for those aged <35 years and <70 years, respectively, relative to the no-treatment scenario. The treatment strategies for patients aged 0 to <35 years, <55 years, <65 years, and <70 years would add 397, 1482, 3782, and 8491 QALYs at a cost of $660, $5930, $4560, and $2530, respectively, per QALY. For the averted TB-related deaths, LTBI treatment targeting those aged 0 to <35 years, <55 years, <65 years, and <70 years would avert 7, 89, 155, and 186 deaths at a cost of $35900, $99200, $111100, and $115700 per deaths, respectively, in 20 years. CONCLUSION: The age-specific expansion policy of LTBI treatment not only for those under 35 years of age but also for those under 65 years of age among household contacts was cost-effective in terms of QALYs and averted TB deaths.

Healthcare use and medical cost before and after diagnosis of nontuberculous mycobacterial infection in Korea: the National Health Insurance Service-National Sample Cohort Study.

BACKGROUND AND OBJECTIVE: The global prevalence and incidence of nontuberculous mycobacterial (NTM) infections are increasing; however, population-level data on healthcare use and medical costs for people with NTM infections are limited. Thus, we investigated the rates of healthcare use and medical costs of people with NTM infections in South Korea using the National Health Insurance Service-National Sample Cohort from 2002 to 2015. METHODS: In this cohort study, people with and without NTM infection aged 20-89 years were matched 1 to 4 by sex, age, Charlson comorbidity index, and year of diagnosis. The overall and annual average healthcare use and medical costs were calculated. In addition, trends in healthcare use and medical costs for each of the 3 years before and after NTM diagnosis were investigated for people diagnosed with NTM infection. RESULTS: A total of 798 individuals (336 men and 462 women) diagnosed with NTM infection and 3192 controls were included in the study. NTM-infected patients had significantly higher rates of healthcare use and medical costs than those in the control group (p < 0.05). NTM-infected patients showed 1.5 times the medical cost and 4.5 times the respiratory disease cost of the control group. People diagnosed with NTM infection incurred the highest medical costs in the 6 months before diagnosis. CONCLUSION: NTM infection increases the economic burden on Korean adults. Appropriate diagnostic tests and treatment plans for NTM infections are needed to reduce the burden of the disease caused by such infection.

Gender differences in tuberculosis patients with comorbidity: A cross-sectional study using national surveillance data and national health insurance claims data in South Korea.

The coexistence of tuberculosis and other chronic diseases complicates disease management. Particularly, the lack of information on the difference in the prevalence of chronic diseases in tuberculosis based on age and gender can hinder the establishment of appropriate public health strategies. This study aimed to identify age- and gender-based differences in the prevalence of chronic diseases as comorbidities in patients with tuberculosis. An anonymized data source was established by linking the national health insurance claims data to the Korean national tuberculosis surveillance data from 2014 to 2018. The prevalence of chronic diseases was stratified by gender and age (age groups: ≤64, 65-74, and ≥75 years), and the differences in the prevalence of chronic diseases were analyzed by multinomial logistic regression and classified using the Charlson Comorbidity Index. A total of 148,055 patients with tuberculosis (61,199 women and 86,856 men) were included in this study. Among the patients aged ≥65 years, 48.2% were female and 38.1% were male. In this age group, the probability of chronic disease comorbidity was higher in female patients than in male patients. The prevalence of congestive heart failure and dementia as comorbidities in patients with tuberculosis increased more drastically with age in women than in men. Thus, the present study confirmed gender and age differences in the distribution of comorbidities among patients with tuberculosis. A more comprehensive gender-responsive approach for patients with tuberculosis and chronic diseases is required to alleviate the double burden of infectious diseases and non-communicable diseases in an aging society.

Comorbidities of nontuberculous mycobacteria infection in Korean adults: results from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database.

BACKGROUND: The global prevalence and incidence of nontuberculous mycobacteria (NTM) infection are increasing. However, the prevalence of NTM infection-associated comorbidities remains understudied. Thus, we investigated the comorbidities associated with NTM infection using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database of the National Health Insurance Service (NHIS). METHODS: In this case-control study, patients with NTM infection and controls aged 20-89 years of age were matched 1:4 by sex, age, region, and income. A total of 26 comorbidities were selected based on previous reports and claims data analysis. The distribution of comorbidities was compared between patients with NTM infection and controls by sex and age using logistic regression analysis. RESULTS: In total, 893 patients (379 men and 514 women) with NTM infection (mean age, 56.1 years) and 3,572 controls (mean age, 55.6 years) were included. The odds ratio for prevalence of respiratory diseases, metabolic diseases, musculoskeletal disorders, gastrointestinal diseases, skin diseases, mental diseases, and neoplasms was significantly higher in patients with NTM infection than in the control group. Among comorbid diseases, the odds ratios (ORs) for the prevalence of the respiratory diseases such as bronchiectasis (OR [95% confidence interval (CI)]: 26.79 [19.69-36.45]) and interstitial pneumonitis (OR [95% CI]: 15.10 [7.15-31.89]) were the highest. No significant differences were observed in NTM infection-related comorbidities between men and women. In the younger age group (20-39 years old), the prevalence of respiratory and systemic diseases such as hypertension and diabetes was higher in the patient group than in the control group. CONCLUSIONS: NTM infection is associated with several respiratory and systemic diseases that should be considered when providing medical care to patients with NTM infection.

Treatment outcome of continuation of intravenous amikacin for Mycobacterium abscessus pulmonary disease with a persistent culture positivity after the treatment initiation.

INTRODUCTION: Whether prolonged intravenous amikacin treatment would lead to better treatment results in patients with Mycobacterium abscessus subspecies abscessus (M. abscessus) pulmonary disease (PD) is unknown. We investigated the efficacy of continued amikacin treatment for the microbiological outcome of M. abscessus PD patients with persistent culture positivity after treatment initiation. METHODS: We retrospectively evaluated 62 patients with M. abscessus PD who were treated with intravenous amikacin and beta-lactams along with a macrolide-based regimen at 3 tertiary referral centers in South Korea. The intravenous antibiotic treatment duration was determined by the attending physician. RESULTS: The median treatment durations with amikacin and beta-lactam in the 62 patients were 25.1 and 8.2 weeks, respectively. The overall microbiological cure rate was 29.0%. Among the 62 patients, 44 showed persistent culture positivity at 8 weeks after treatment with an amikacin-containing multidrug regimen. The median parenteral amikacin treatment duration after 8 weeks in these patients was 18.0 weeks. The conditional probability of microbiological cure with continuation of the amikacin-containing regimen in these patients was 18.2% (95% confidence interval 8.2-32.7). Additionally, the conditional probability of microbiological cure in the 34 patients with persistent culture positivity at 12 weeks was 8.8% (95% confidence interval 1.9-23.7). After 16 weeks, the conditional probability of microbiological cure decreased further, reaching 0% at 28 weeks after treatment initiation. CONCLUSION: The continuation of intravenous amikacin therapy was usually not followed by culture conversion in M. abscessus PD patients with persistent sputum culture positivity after treatment initiation.

Impact of prognostic nutritional index on outcomes in patients with Mycobacterium avium complex pulmonary disease.

Onodera's prognostic nutritional index (PNI) is useful in predicting prognosis of various diseases. But the usefulness of PNI in non-surgical patients has not been sufficiently proven yet. In patients with mycobacterium avium complex pulmonary disease (MAC-PD), malnutrition is an important factor that affects the quality of life and morbidity. Here, we aimed to evaluate whether PNI is related with clinical outcomes in MAC-PD patients. We examined 663 patients diagnosed with MAC-PD between May 2005 and November 2017. PNI score was calculated at the time of diagnosis and treatment initiation, and patients were divided into malnutrition and non-malnutrition groups according to a cut-off PNI score of 45. As the recommended duration of treatment for MAC-PD is 12 months following sputum conversion, treatment duration less than 12 months was defined as treatment intolerance. Survivals were compared with the log-rank test. Multivariate logistic regression and multivariate Cox proportional hazards models were used to estimate the odds ratio (OR) and hazards ratio (HR) for treatment intolerance and mortality, respectively. Of the 306 patients that received treatment, 193 received treatment longer than 12 months. In the multivariable logistic regression model, malnutrition at the time of treatment initiation was related with treatment intolerance (OR: 2.559, 95% confidence interval [CI]: 1.414-4.634, P = 0.002). Patients in the malnutrition group at the time of diagnosis exhibited lower survival (P<0.001) and malnutrition at the time of diagnosis was a significant risk for all-cause mortality (HR: 2.755, 95% CI: 1.610-4.475, P<0.001). Malnutrition, as defined by PNI, is an independent predictor for treatment intolerance and all-cause mortality in patients with MAC-PD.

Prevalence, incidence, and mortality of nontuberculous mycobacterial infection in Korea: a nationwide population-based study.

BACKGROUND: Epidemiologic characteristics of nontuberculous mycobacterial (NTM) disease remain largely unknown. The objective of this study was to evaluate incidence, prevalence, and mortality of NTM infection in a large nationwide population-based cohort in Korea. METHODS: Data of the National Health Insurance Service database, an extensive health-related database including most Korean residents, were used. Adults with a primary diagnosis of NTM as determined by International Classification of Disease-Tenth Revision coding (A31) were identified between 2003 and 2016. Incidence, prevalence, and mortality of NTM infection were analyzed. RESULTS: A total of 46,194 individuals had a primary diagnosis of NTM infection. Their mean age was 55.8 years. Of these subjects, 61.1% were females. Annual age-adjusted incidence and prevalence of NTM infection tended to increase rapidly from 2003 to 2016. Age-adjusted incidence and prevalence was 17.9 and 33.3 per 100,000 population in 2016. The incidence and prevalence were higher in females and the elderly. The 5-year mortality rate in the population with NTM infection was 17.8%. The standardized mortality ratio of patients with NTM infection to the general population was 2.16 (95% confidence interval: 2.10 to 2.22). CONCLUSIONS: This large population-based study showed that the incidence and prevalence of NTM infection in Korea increased rapidly from 2003 to 2016. They were higher in women and the elderly. The mortality rate in the population with NTM infection was higher than that in the general population.

Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes.

RATIONALE: 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. OBJECTIVES: To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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).

Comparison of levofloxacin versus moxifloxacin for multidrug-resistant tuberculosis.

RATIONALE: Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. OBJECTIVES: To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. METHODS: In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27-2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). CONCLUSIONS: The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).