Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Assessment of the Correlation between Endoscopic Activity and Histological Activity in Ulcerative Colitis Patients.

OBJECTIVE: The aim of this study was to assess the concordance between the Rachmilewitz endoscopic activity index (EAI) and the Harpaz histopathological activity scoring system (HSS), which are used for evaluating the disease activity of ulcerative colitis (UC). SUBJECTS AND METHODS: This study included 109 patients with UC. Based on the disease extent, patients were divided into two groups as left-sided colitis and pancolitis. Patients were grouped as inactive, mild, moderate and severe depending on the Rachmilewitz EAI and Harpaz HSS. Kendal's tau and kappa (x03BA;) statistics were used to assess the agreement between endoscopic and histopathological scores. A receiver operating characteristic (ROC) curve was also analyzed to evaluate the sensitivity and specificity of endoscopic scores to predict inactive histopathological disease. RESULTS: In the left-sided colitis group, there were slight and poor agreements in the inactive endoscopic subscores (ESS) with inactive Harpaz HSS (x03BA;: 0.598, p < 0.001) and moderate ESS with moderate Harpaz HSS (x03BA;: 0.236, p = 0.046). There was no agreement between mild ESS and mild Harpaz HSS and between severe ESS and severe Harpaz HSS (x03BA;: 0.071, p = 0.573 and x03BA;: 0.160, p = 0.151, respectively). In the pancolitis group, there was no significant agreement between inactive, mild, moderate and severe ESS and the equivalent Harpaz HSS grades (x03BA;: -0.194, p = 0.187; x03BA;: 0.125, p = 0.397; x03BA;: 0.148, p = 0.175 and x03BA;: 0.174, p = 0.153, respectively). The ROC curve showed that the ESS indicating inactive disease had a low sensitivity to predict histologically inactive disease. CONCLUSION: The concordance between the endoscopic and histopathological indices was poor. Using both scores in the follow-up of patients with UC is necessary for treatment planning.

[Quality assessment of microscopic examination in tuberculosis diagnostic laboratories: a preliminary study]. / Tüberküloz tani laboratuvarlarinda mikroskopi kalite degerlendirme pilot uygulamasi

Recently, the diagnosis of pulmonary tuberculosis (TB) has based on smear microscopy in the Direct Observed Treatment Strategy (DOTS) programme which provides the basis of treatment worldwide. Microscopic detection of AFB (Acid-Fast Bacilli) is one of the main components in the National TB Control Programmes (NTCP). Precision level in microscopy procedures and evaluations are the most important steps for accurate diagnosis of the disease and to initiate proper treatment. Therefore, the external quality assessment (EQA) is the most important implement to provide the reliability and validity of tests. In countries where NTCP are performed, this task is fulfilled by the National Reference Laboratories (NRL) according to the guidelines of the World Health Organization (WHO). For this purpose a pilot study was initiated by the central NRL of Turkey for EQA of AFB smear microscopy as part of the NTCP on January 1, 2005. A total of 5 laboratories of which 2 were district TB laboratories (A, B), 2 were tuberculosis control dispensaries (C, D), 1 was a national reference laboratory (E), participated in this study. Blind re-checking method (re-examination of randomly selected slides) was used for the evaluation, and the slides were sent to the central NRL with 3 months interval, four times a year, selected according to LQAS (Lot Quality Assurance Sampling) guides. In the re-evaluation of the slides, false positivity (FP), false negativity (FN) and quantification errors (QE) were noted. Laboratory A, sent totally 525 slides between January 1, 2005 and April 1, 2008. In the result of re-checking, 514 (97.9%) slides were found concordant, and 11 (2.1%) were discordant (10 FP, 1 FN). Laboratory B, participated in the study between October 1, 2005 and July 1, 2006 and of the 67 re-examined slides, 60 (89.5%) were concordant and 7 (10.5%) were discordant (2 FP, 0 FN, 5 QE). Laboratory C, sent 235 slides between January 1, 2005 and April 1, 2006; of them 218 (92.8%) were detected as compatible and 17 (7.2%) slides were incompatible (4 FP, 9 FN, 4 QE). Laboratory D, participated in QC for only once between January 1, 2008 and April 1, 2008; and all the 50 slides were found compatible, with no FP, FN and QE. Laboratory E, was included in the study between January 1, 2005 and January 1, 2008 and of the 696 re-checked slides, 690 (99.1%) were reported as compatible and 6 (0.9%) were incompatible (3 FN, 3 QE). Following EQA, on-site evaluation of the laboratories with major errors, was performed and necessary adjustments and training were done. In conclusion, external quality control measures for AFB microscopy is crucial and essential for the tuberculosis laboratory performances for accurate and reliable results.