Comparison of the Diagnostic Performance of MeltPro and Next-Generation Sequencing in Determining Fluoroquinolone Resistance in Multidrug-Resistant Tuberculosis Isolates.
J Mol Diagn
; 25(6): 342-351, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-37208048
ABSTRACT
This study systematically investigated the performance of MeltPro and next-generation sequencing in the diagnosis of fluoroquinolone (FQ) resistance among multidrug-resistant tuberculosis patients and explored the relationship between nucleotide alteration and the level of phenotypic susceptibility to FQs. From March 2019 to June 2020, a feasibility and validation study with both MeltPro and next-generation sequencing was performed in 126 patients with multidrug-resistant tuberculosis. Using phenotypic drug susceptibility testing as the gold standard, 95.3% (82 of 86) of ofloxacin-resistant isolates were identified correctly by MeltPro. In addition, whole-genome sequencing was able to detect 83 phenotypically ofloxacin-resistant isolates. The isolates with an individual gyrB mutation outside the quinolone resistance-determining region (QRDR) had minimum inhibitory concentrations (MICs) of ≤2 µg/mL. Despite showing low MICs close to the breakpoint for isolates carrying only gyrA_Ala90Val, the combined mutation gyrB_Asp461Asn caused the ofloxacin MIC to be eight higher than that obtained in Mycobacterium tuberculosis (MTB) isolates with the Ala90Val mutation alone (median, 32 µg/mL; P = 0.038). Heteroresistance was observed in 12 of 88 isolates harboring mutations in the QRDRs. In conclusion, our data show that MeltPro and the whole-genome sequencing assay correctly can identify FQ resistance caused by mutations in the gyrA QRDR. The combined gyrB_Asp461Asn mutation may significantly decrease in vitro FQ susceptibility of MTB isolates with low-level-resistance-associated gyrA mutations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis Resistente a Múltiples Medicamentos
/
Mycobacterium tuberculosis
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Mol Diagn
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
China