Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients

Abstract

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.

Molecular clustering of patients with diabetes and pulmonary tuberculosis: A systematic review and meta-analysis

“…A TB control program pioneer in the use of RFLP-IS6110 in operational conditions, showed an overall concordance in clustering of 79% and highly similar discriminatory power in the two methods when typing 3,978 M. tuberculosis isolates [ 97 ]. Our study is also limited by the fact that reviewed studies did not consider the increasing evidence of within patient microdiversity arising both from “de novo” mutations and mixed infections [ 98 , 99 ]. As a consequence, samples taken from the upper airway (as occurred in the majority of included studies in this review) captured only a fraction of the bacterial population diversity.…”