Co-resistance to isoniazid and second-line anti-tuberculosis drugs in isoniazid-resistant tuberculosis at a tertiary care hospital in Thailand.

Isoniazid-resistant tuberculosis (Hr-TB) is an important drug-resistant tuberculosis (TB). In addition to rifampicin, resistance to other medications for Hr-TB can impact the course of treatment; however, there are currently limited data in the literature. In this study, the drug susceptibility profiles of Hr-TB treatment and resistance-conferring mutations were investigated for Hr-TB clinical isolates from Thailand. Phenotypic drug susceptibility testing (pDST) and genotypic drug susceptibility testing (gDST) were retrospectively and prospectively investigated using the Mycobacterium Growth Indicator Tube (MGIT), the broth microdilution (BMD) method, and whole-genome sequencing (WGS)-based gDST. The prevalence of Hr-TB cases was 11.2% among patients with TB. Most Hr-TB cases (89.5%) were newly diagnosed patients with TB. In the pDST analysis, approximately 55.6% (60/108) of the tested Hr-TB clinical isolates exhibited high-level isoniazid resistance. In addition, the Hr-TB clinical isolates presented co-resistance to ethambutol (3/161, 1.9%), levofloxacin (2/96, 2.1%), and pyrazinamide (24/118, 20.3%). In 56 Hr-TB clinical isolates, WGS-based gDST predicted resistance to isoniazid [katG S315T (48.2%) and fabG1 c-15t (26.8%)], rifampicin [rpoB L430P and rpoB L452P (5.4%)], and fluoroquinolones [gyrA D94G (1.8%)], but no mutation for ethambutol was detected. The categorical agreement for the detection of resistance to isoniazid, rifampicin, ethambutol, and levofloxacin between WGS-based gDST and the MGIT or the BMD method ranged from 80.4% to 98.2% or 82.1% to 100%, respectively. pDST and gDST demonstrated a low co-resistance rate between isoniazid and second-line TB drugs in Hr-TB clinical isolates. IMPORTANCE: The prevalence of isoniazid-resistant tuberculosis (Hr-TB) is the highest among other types of drug-resistant tuberculosis. Currently, the World Health Organization (WHO) guidelines recommend the treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months. The susceptibility profiles of Hr-TB clinical isolates, especially when they are co-resistant to second-line drugs, are critical in the selection of the appropriate treatment regimen to prevent treatment failure. This study highlights the susceptibility profiles of the WHO-recommended treatment regimen in Hr-TB clinical isolates from a tertiary care hospital in Thailand and the concordance and importance of using the phenotypic drug susceptibility testing or genotypic drug susceptibility testing for accurate and comprehensive interpretation of results.

Clinical characteristics and drug susceptibility profiles of Mycobacterium abscessus complex infection at a medical school in Thailand.

OBJECTIVES: This study investigated the differences in epidemiological and clinical data, and antimicrobial susceptibilities among different subspecies of Mycobacterium abscessus complex (MABSC) clinical isolates at a medical school in Thailand. METHODS: A total of 143 MABSC clinical isolates recovered from 74 patients were genotypically analyzed for erm(41), rrl, and rrs mutations, and antimicrobial susceptibilities were determined using a broth microdilution method. Patient characteristics and clinical outcomes were reviewed from the medical records. RESULTS: Seventy-four patients were infected with 28/74 (37.8%) M. abscessus subspecies abscessus (MAB), 43/74 (58.1%) M. abscessus subsp. massiliense (MMA), and 3/74 (4.1%) M. abscessus subsp. bolletii (MBO). The clinical findings and outcomes were generally indistinguishable between the three subspecies. All three subspecies of MABSC clinical isolates exhibited high resistance rates to ciprofloxacin, doxycycline, moxifloxacin, TMP/SMX, and tobramycin. MAB had the highest resistance rates to clarithromycin (27.8%, 20/72) and amikacin (6.9%, 5/72) compared to MBO and MMA, with p < 0.001 and p = 0.004, respectively. In addition, the rough morphotype was significantly associated with resistance to amikacin (8.9%, 5/56), clarithromycin (26.8%, 15/56), and imipenem (76.8%, 43/56) (p < 0.001), whereas the smooth morphotype was resistant to linezolid (57.1%, 48/84) (p = 0.002). In addition, T28 of erm(41), rrl (A2058C/G and A2059C/G), and rrs (A1408G) mutations were detected in 87.4% (125/143), 16.1% (23/143), and 9.1% (13/143) of MABSC isolates, respectively. CONCLUSIONS: Three MABSC subspecies caused a variety of infections in patients with different underlying comorbidities. The drug susceptibility patterns of the recent circulating MABSC strains in Thailand were different among the three MABSC subspecies and two morphotypes.

Determination of specific autoantibodies in patients with systemic lupus erythematosus by Line immunoassay, ELISA and CLIF assay.

BACKGROUND: Detection of specific antinuclear-antibodies is very importance in term of diagnosis, prognosis and management of patients with systemic lupus erythematosus (SLE). To date, Line immunoassay (LIA), enzyme-linked immunosorbent assay (ELISA) and Crithidia luciliae indirect immunofluorescence (CLIF) assay are commonly used for detection of specific antinuclear-antibodies. OBJECTIVE: To determine the performance of LIA, ELISA and CLIF for the detection of anti-double-stranded DNA (dsDNA), anti-nucleosome, and anti-extractable nuclear antigens (ENA) antibodies in patients with SLE. METHODS: A total 100 sera from 50 patients with SLE, 25 patients with disease control and 25 healthy control subjects were tested for anti-dsDNA, anti-nucleosome, and anti-ENA antibodies by LIA, ELISA, and CLIF assay. Agreement and diagnostic performance of each assay were analyzed using Cohen's kappa coefficient and receiver operating characteristic curve analysis. RESULTS: For the detection of anti-dsDNA antibody, ELISA had a substantial agreement with CLIF assay (? = 0.74) but LIA had a fair agreement with ELISA and CLIF assay (? = 0.37, and 0.35 respectively). For the detection of anti-nucleosome, anti-nRNP/Sm, anti-Sm, anti-SSA, and anti-SSB antibodies, LIA had a substantial to perfect agreement with ELISA (? = 0.64, 0.78, 0.68, 0.91, and 0.74, respectively). Anti-dsDNA-NcX ELISA and anti-dsDNA CLIF assay had equally diagnostic performance (sensitivity, 66% vs. 68%, and specificity, 96% vs. 94%, respectively) whereas, anti-dsDNA LIA has low sensitivity (22%) but high specificity (100%). CONCLUSIONS: LIA, ELISA, and CLIF demonstrated comparable performance for the detection of specific antinuclear-antibodies. However, there were some discrepancy between assays particularly in the detection of anti-dsDNA antibody.