Specific gyrA Gene Mutations Correlate with High Prevalence of Discordant Levofloxacin Resistance in Mycobacterium tuberculosis Isolates from Beijing, China
| Autor: | Shanshan Li, Yunxu Li, Lingling Dong, Yifeng Ma, Yu Pang, Yuanyuan Shang, Fengmin Huo, Yi Xue |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
DNA
Bacterial 0301 basic medicine Tuberculosis Sequence analysis Gyra gene Antitubercular Agents Levofloxacin Microbial Sensitivity Tests Drug resistance DNA gyrase Pathology and Forensic Medicine Microbiology Mycobacterium tuberculosis chemistry.chemical_compound symbols.namesake 03 medical and health sciences Minimum inhibitory concentration 0302 clinical medicine Genotype Drug Resistance Bacterial Tuberculosis Multidrug-Resistant Prevalence medicine Humans Tuberculosis Pulmonary Retrospective Studies Sanger sequencing biology Middlebrook 7H9 broth Sequence Analysis DNA Molecular diagnostics medicine.disease biology.organism_classification 030104 developmental biology chemistry DNA Gyrase Beijing 030220 oncology & carcinogenesis Mutation symbols Molecular Medicine medicine.drug |
| Zdroj: | The Journal of Molecular Diagnostics. 22:1199-1204 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2020.06.010 |
| Popis: | Although molecular diagnostics are highly sensitive in the diagnosis of fluroquinolone (FQ)-resistant tuberculosis (TB), the discordant results with the sequential phenotypic drug susceptibility testing (DST) invariably occur. To investigate the prevalence and the cause of discordant results between molecular and phenotypic DST for levofloxacin (LFX), the cases who were determined to be LFX-susceptible using the phenotypic DST but LFX-resistant using the MeltPro assay were retrospectively reviewed in Beijing, China. We measured LFX minimal inhibitory concentrations (MICs) using Middlebrook 7H9 broth. Sanger sequencing was used to determine genotypic characteristics of discordant isolates. Between January and December 2018, 126 (22.1%) out of 571 smear-positive TB patients were identified as LFX-resistant TB by MeltPro assay. Among the 126 LFX-resistant TB, there were 34 isolates identified as LFX-susceptible TB by phenotypical DST. This result demonstrated a discordance prevalence of 27.0%. LFX MICs were majorly centered around the critical concentration, and 7 (21.2%) and 13 (39.4%) had MICs of 2.0 mg/l and 4.0 mg/l, respectively. The most prevalent mutations conferring discordant LFX resistance were the amino acid substitutions of Ser to Leu in 90 codon (13, 39.4%) and Asp to Ala in 94 codon ofgyrA(11, 33.3mg/l belonged to Ala90Val and Asp94Ala group. In conclusion, our data demonstrate that more than one quarter of LFX-resistant isolates by molecular method are susceptible to LFX using the phenotypic DST. The high prevalence of discordant LFX resistance is majorly due to the isolates with specific mutations withingyrAgene conferring proximity of MICs to the critical concentration. |
| Databáze: | OpenAIRE |
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