Jae Joon Yim

The drug susceptibility profile and inducible resistance to macrolides of Mycobacterium abscessus and Mycobacterium massiliense in Korea

We conducted drug susceptibility testing (DST) against various antimicrobial agents, including new candidate drugs, and investigated the relationship between inducible resistance (IR) to macrolides and erm(41) gene in Mycobacterium abscessus complex. Sixty-two isolates of M. abscessus complex from 2 tertiary care hospitals in South Korea were tested against 10 antimicrobial agents. Thirty-five isolates were M. abscessus, and 27 were Mycobacterium massiliense. Amikacin, moxifloxacin, linezolid, clofazimine, and tigecycline were active against most isolates and cefoxitin and ciprofloxacin against moderate number of isolates. M. massiliense remained susceptible to macrolides; in contrast, M. abscessus became highly resistant on day 14 after incubation. DST pattern did not differ between clarithromycin and azithromycin. IR to clarithromycin was correlated with erm(41) genotype in M. abscessus. Variations in susceptibility to antimicrobial agents within species and the difference in DST patterns between M. abscessus and M. massiliense suggest that DST and identification of M. abscessus complex are significant before treatment.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis

BACKGROUNDnMedical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis.nnnMETHODSnIndividual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated.nnnRESULTSnA total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%).nnnCONCLUSIONSnPartial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Standardization of multilocus sequence typing scheme for Mycobacterium abscessus and Mycobacterium massiliense.

This study aims to develop a multilocus sequence typing (MLST) scheme for Mycobacterium abscessus complex for the typing of stains within each species. A total of 89 clinical isolates of M. abscessus complex from 71 patients of 2 tertiary care hospitals in South Korea were included. Forty-two isolates were identified as M. abscessus, and 29, as Mycobacterium massiliense through sequencing of 8 housekeeping genes and rpoB. The MLST scheme identified 26 different sequence types(STs) and 13 different clonal complexes (CCs) in M. abscessus and 12 different STs and 6 different CCs in M. massiliense. The MLST data showed high concordance with the XbaI-macrorestriction patterns of pulsed-field gel electrophoresis in the duplicated isolates. Our MLST schemes could identify different strains of M. abscessus and M. massiliense, and the schemes also showed a reliable reproducibility. Therefore, our MLST schemes may be useful in studying the epidemiology of M. abscessus and M. massiliense infections.

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

RATIONALEnWe 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.nnnOBJECTIVESnTo compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin.nnnMETHODSnA 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.nnnMEASUREMENTS AND MAIN RESULTSnTreatment 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 (Pu2009=u20090.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, Pu2009=u20090.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, Pu2009=u20090.54) and treatment success rates (84.4 vs. 79.7%, Pu2009=u20090.53) 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, Pu2009=u20090.11 on liquid media; 17.0 vs. 42.0 d, Pu2009=u20090.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, Pu2009=u20090.03), especially musculoskeletal ones (37.7 vs. 14.9%, Pu2009=u20090.001).nnnCONCLUSIONSnThe 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).

Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease

Background Recently, increased levels of high-mobility group box 1 protein (HMGB1) have been identified in various inflammatory conditions and infections. However, no studies have evaluated the HMGB1 level in nontuberculous mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease. Methods A total of 60 patients newly diagnosed with NTM lung disease, 44 culture-positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were included in this study. The serum HMGB1 concentrations were quantified using HMGB1 enzyme-linked immunosorbent assay kits. Results Serum HMGB1 level in patients with pulmonary TB or NTM lung disease, was significantly lower than that of the healthy controls. In addition, the serum HMGB1 level in TB patients was significantly lower than patients with NTM lung disease. However, the levels in NTM patient subgroups did not differ according to the causative species, disease progression, and disease phenotype. Conclusion Although low levels of serum HMGB1 has the potential to be a marker of mycobacterial lung disease, these levels were unable to differentiate disease progression and disease phenotype in NTM lung diseases.