Dataset Information

Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System.

ABSTRACT: To find the potential reasons for the discrepancies in the drug susceptibility test (DST) of M. tuberculosis isolates, twenty paired isolates with disputed drug susceptibilities to isoniazid (INH) were selected according to the MGIT960 testing and Löwenstein-Jensen (L-J) proportion methods. Their MICs were confirmed again by broth microdilution method and by L-J proportion method. The spoligotyping results showed that, of all the 20 paired strains, 11 paired isolates belonged to the Beijing genotype and 6 paired isolates belonged to SIT1634, and that each of the remaining 3 paired isolates had two genotypes, namely, SIT1 and SIT1634. Those 3 paired isolates with different intrapair spoligotypes were further confirmed as mixed infection by the results that those three pairs of isolates with different 12 locus MIRU intrapair types and one pair carried different base pair at codon 315 (AGC versus AAC). Totally mutations in the katG gene were identified in 13 paired isolates. No mutations were found in the regulatory sequences and open reading frames (ORF) of the inhA and ahpC genes in any of the tested isolates. Those results showed that the different test systems and the mixed infection with particular genotypes of M. tuberculosis strains contributed to the drug susceptibility discrepancies.

SUBMITTER: Mei Z

PROVIDER: S-EPMC4433640 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System.

Mei Zaoxian Z Sun Zhaogang Z Bai Dapeng D Xu Yuhui Y Li Zhiling Z Huang Hairong H Li Chuanyou C Xu Shaofa S Li Li L

BioMed research international 20150503

To find the potential reasons for the discrepancies in the drug susceptibility test (DST) of M. tuberculosis isolates, twenty paired isolates with disputed drug susceptibilities to isoniazid (INH) were selected according to the MGIT960 testing and Löwenstein-Jensen (L-J) proportion methods. Their MICs were confirmed again by broth microdilution method and by L-J proportion method. The spoligotyping results showed that, of all the 20 paired strains, 11 paired isolates belonged to the Beijing geno ...[more]

PMID: 26064938

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Project description:OBJECTIVE:The objective of the research was to assess the susceptibility of the slowly growing nontuberculous mycobacteria strains to the antimicrobial drugs used for mycobaterioses treatment using SLOMYCO test system. MATERIALS AND METHODS:We assessed 363 NTM strains: 177 MAC (161 M. avium, 16 M. intracellulare), 112 M. kansasii and 74 M. xenopi collected from the respiratory material of the patients were under the treatment or under diagnostic procedures at our Center, affiliates and the diagnostic department in 2010-2016. Drug sucseptibility for NTM was tested using the Sensititre SLOWMYCO system (TREK DIAGNOSTIC Systems Ltd., UK). MICs were established by microdilutions in Mueller-Hinton broth on polystyrene 96-well plates. The statistical analysis was done using the StatGraphics Plus 5.0 software. The data were compared pairwise using Pearson ?2 test with Yates correction. 95% confidence interval (CI) were calculated. Statistically significant differences were considered for p <0.05. Log-rank test and Kaplan-Meier curves were used to assess the concentration-dependent surveillance probability. RESULTS:The statistically significant differences were revealed in sensitivity/resistance isolates of M. avium and M. intracellulare: M. avium strains were resistant to higher concentrations of amikacin, clarithromycin, linezolid and streptomycin (p <0.01); M. intracellulare strains were resistant to higher concentrations of ethionamide (p <0.05). The isolates of M. avium were significantly more resistant than M. kansasii to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifabutin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). The isolates of M. avium showed significantly higher resistance than M. xenopi to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). Statistically significant differences in the dynamics of the response to the antibacterial effects of isoniazid, linezolid, moxifloxacin, rifampicin, trimethoprim/sulfamethoxazole, ethambutol, and ethionamide were found for M. intracellulare and M. xenopi (complete inhibition of the visible growth of M. intracellulare required higher drugs concentrations, p <0, 05). Comparison of the Kaplan-Meyer curves revealed statistically significant differences in survialence probability of M. kansasii and M. xenopi for amikacin, doxycycline, rifampicin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (a higher number of isolates of M. xenopi were inhibited by low drugs concentrations, p <0.05). CONCLUSIONS:Our data show that M. avium and M. intracellulare were more resistant to the majority of the studied drugs than M. kansasii and M. xenopi.

Project description:Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid.We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions.Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 ?g per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 ?g per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 ?g per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater.This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).

Dataset Information

Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System.

Publications

Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System.

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