Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study [post]

2020 unpublished
The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15-34 years), middle (35-59 years), and older (≥60 years) to compare drugresistance patterns. Results: Among the 4,417
more » ... Among the 4,417 cases investigated, 179 (4.1%), 53 (1.2%), and 316 (7.2%) were multidrugresistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were similar among the three groups (11.2%, 12.2%, and 10.4% in the younger, middle, and older groups, respectively). MDR/RR-TB case numbers decreased significantly as age increased (8.6%, 6.3%, 3.3%, respectively). Proportions of MDR/RR-TB among retreated patients in the younger generation decreased from 50.0% to 18.2%, but remained higher than that in the older generation. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients. Background Drug-resistant tuberculosis (DR-TB) is a major global public health concern [1]. A 95% reduction in TB mortality and 90% reduction in its incidence compared to that in 2015 should be achieved by 2035 according to the World Health Organization (WHO)'s End TB strategy [2]. Preventing the spread of DR-TB is important for the elimination of TB [3]. Multidrug-resistant TB (MDR-TB), which is resistant to isoniazid (INH) and rifampicin (RIF), is another obstacle because of its high treatment costs and unsatisfactory outcomes. Although anti-TB drug resistance rates declined after improved treatment efficiency in South Korea in the 1980s, nationwide drug surveillance conducted between 1994 and 2004 revealed that drug previous TB treatment, the predominant incident MDR-TB etiology has now shifted to direct person-toperson MDR strain transmission [13]. A recent study suggested that > 80% of incident MDR-TB cases in most present-day epidemic settings result from transmission of MDR-TB [14]. Therefore, to control the MDR-TB epidemic in young patients, primary MDR-TB transmission and infection control and appropriate patient management should be prioritized in South Korea. In 2011, the Korean government implemented a national public-private TB control project, providing comprehensive TB patient management and treatment success rates among MDR-TB cases increased from 54.1% in 2014 to 64.3% in 2016 [7]. Furthermore, the percentage of MDR/RR-TB cases among young patients with prior TB history decreased dramatically between 2015 and 2016. According to the revised WHO DR-TB treatment guidelines [15], levofloxacin is essential to MDR/RRand Hr-TB treatment. FQs are widely used antimicrobial agents in out-and in-patient treatment, and its use in patients with TB at a single tertiary hospital in South Korea, regardless of their DR status, was also high [16] . Here, the percentage of FQ-resistant cases was the highest among that to secondline drugs, especially in young patients with prior anti-TB treatment history. In our study population, proportion of FQ resistance in both RR-TB and Hr-TB was low at 1.9% and 1.3%, respectively, which implies safe addition of levofloxacin to regimens according to the revised WHO guideline [15]. However, 26% of young patients with MDR-TB in our study population showed resistance to any FQs, implying a high public health burden in the younger generations. In addition, 25% of RIF-and INHsusceptible patients were resistant to any FQs, which is higher than results reported in a recent multicountry surveillance study [17] . Such a high prevalence of FQ resistance may be due to the widespread use of FQs in various clinical settings [16] . Several studies showed that FQ exposure prior to TB diagnosis was associated with FQ resistance [18] . Therefore, the implementation of FQ prescription antibiotic stewardship programs for drug-susceptible TB should be considered in South Korea. This study had several limitations. First, although we hypothesized that drug resistance profiles may differ among various age groups due to rapid and intense socioeconomic changes in late 20th century
doi:10.21203/rs.3.rs-17875/v1 fatcat:pjw56bv7h5buvfqaicjxrrzh4m