Abstract
Whole-genome sequencing (WGS) is promising for the quality control of laboratory facilities for Mycobacterium tuberculosis (MTB) strains. We describe the clinical and laboratory characteristics of false positive versus true positive MTB cultures based on WGS, which were experienced in a real clinical setting. Strain harvest and DNA extraction from seven isolates from pre-extensive drug-resistant (pre-XDR) TB patients transferred to the Korea University Ansan Hospital were performed, and epidemiologic links and clinical information, including the phenotypic drug susceptibility test (pDST), were investigated. WGS was performed using Ion GeneStudio with an ION530tm chip (average sequencing depth, ~100-fold). In the phylogenetic tree, identical and different strains were distributed separately. Five of the seven isolates were identical; the remaining two isolates differed from the others. The images of the referred pre-XDR-TB patients with false positive MTB that were analyzed were of regions close to old TB scars. Further, the results of WGS gene mutation analysis for ethambutol, streptomycin, and fluoroquinolone resistance in all six patients were not concordant with the pDST results. WGS and clinical information were useful in differentiating laboratory cross-contamination from true positive TB, thereby avoiding the unnecessary treatment of false positive patients and delay in treating true positive TB patients, with reliable genotypic drug resistance results.
Highlights
Tuberculosis (TB) remains a global threat, and its outbreaks have an enormous social impact [1,2]
We describe the clinical and laboratory characteristics of false positive versus true positive Mycobacterium tuberculosis (MTB) cultures based on Whole-genome sequencing (WGS), showing that genomics can be used in clinical practice and quality control
Identical and different strains were distributed separately. Combining these results with clinical information, we found that the five identical strains resulted from laboratory cross-contamination, and the other two strains were true pre-extensive drug-resistant TB without epidemiological links (Figures 1 and 2)
Summary
Tuberculosis (TB) remains a global threat, and its outbreaks have an enormous social impact [1,2]. Laboratory cross-contamination mimicking outbreaks is a significant problem, especially with multidrug-resistant (MDR) TB strains [3,4]. Genotyping and molecular studies play an important role in investigating laboratory cross-contamination [5]. Cross-contamination is suspected when a TB strain matches the genotype of another isolate processed during the same period in a laboratory institute, without epidemiological links [6]. Cross-contamination results in unnecessary expense arising from contact investigation and drug treatments with serious side effects [7]. Whole-genome sequencing (WGS) shows promise in the quality control of Mycobacterium tuberculosis (MTB) laboratory cultures because it is faster and more accurate than
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