Date Published: April 25, 2019
Publisher: Public Library of Science
Author(s): Eun-Jung Jo, Seyeon Park, Kyu Min Lee, Insu Kim, Jung Seop Eom, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jeongha Mok, Frederick Quinn.
This study investigated the time to appropriate treatment and factors affecting late treatment initiation in patients with multidrug-resistant tuberculosis (MDR-TB) in South Korea.
Data from patients with culture-confirmed pulmonary MDR-TB who received treatment at Pusan National University Hospital (PNUH) between January 2010 and July 2018 were reviewed retrospectively. Patients were divided into two groups according to the first institution they visited [patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) and patients who were initially diagnosed with TB at PNUH (Group B)].
A total of 100 patients were included (53 in Group A and 47 in Group B). The percentage of patients in whom line probe assays (LPAs) for isoniazid and rifampin or Xpert MTB/RIF assays were performed was higher in Group B than in Group A [20.8 vs. 57.4% (P < 0.001) and 17.0 vs. 46.8% (P = 0.001), respectively]. The median time from the first visit to appropriate treatment initiation was longer in Group A (102.0 vs. 77.0 days, P = 0.002). However, a subgroup analysis of patients with pre-extensively or extensively drug-resistant TB (pre-XDR- or XDR-TB) revealed that the time to appropriate treatment did not differ between Groups A and B. Although the time to appropriate treatment decreased during the study period in both Groups A and B, this trend was not evident in patients with pre-XDR- or XDR-TB in Group B. Based on multivariate analyses, performance of LPAs for isoniazid and rifampin, performance of Xpert MTB/RIF assays, and the presence of uncomplicated MDR-TB were protective against delays in appropriate treatment initiation. The time to appropriate treatment in patients with MDR-TB in South Korea was not acceptable, particularly for patients diagnosed outside of PNUH and for patients with pre-XDR- or XDR-TB. The use of rapid molecular drug susceptibility tests in various healthcare settings and introduction of second-line LPAs are required.
Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem worldwide that complicates control and elimination of TB [1,2]. Treatment for MDR-TB is prolonged, as second-line drugs are less effective and more toxic than first-line drugs . Thus, treatment outcomes are often unsatisfactory. In a 2015 global MDR-TB cohort, only 55% of patients successfully completed treatment . The treatment outcomes of patients with extensively drug-resistant TB (XDR-TB) were poor because only 34% of patients completed treatment successfully .
The present study revealed that the time from the first institution visit to initiation of appropriate MDR-TB treatment was longer for patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) than for patients who were initially diagnosed with TB at PNUH (Group B). Although the time to treatment for all MDR-TB patients in both groups decreased during the study period, the time itself was not acceptable, particularly for Group A. In patients with pre-XDR- or XDR-TB, there was no difference in the time to treatment between Group A and Group B, and there was no evidence of a decreasing time to appropriate treatment in Group B during the study period. Our results highlight several concerns regarding diagnosis and treatment of MDR-TB in South Korea: (1) a lack of rapid molecular DST use in institutions other than tertiary referral hospitals or designated TB care centers; (2) a delay in diagnosis of pre-XDR- and XDR-TB using currently available methods, even in well-equipped institutions, and the need for other DST methods able to rapidly detect FQ and SLID resistance; and (3) the possibility of transmission of this difficult-to-treat pathogen within the community in cases of inappropriate treatment.