Correlating Minimum Inhibitory Concentrations of ofloxacin and moxifloxacin with gyrA mutations using the genotype MTBDRsl assay

To correlate gyrA mutations found on the Genotype MTBDRsl assay in Mycobacterium tuberculosis (MTB) isolates with Minimum Inhibitory Concentrations (MICs) to the fluoroquinolones compounds ofloxacin (OFX) and moxifloxacin (MXF). MICs for OFX and MXF were ascertained for 93 archived clinical MTB isol...

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Published in:Tuberculosis (Edinburgh, Scotland) Scotland), 2015-03, Vol.95 (2), p.137-141
Main Authors: Kambli, Priti, Ajbani, Kanchan, Sadani, Meeta, Nikam, Chaitali, Shetty, Anjali, Udwadia, Zarir, Rodwell, Timothy C., Catanzaro, Antonino, Rodrigues, Camilla
Format: Article
Language:English
Subjects:
Antitubercular Agents - pharmacology
DNA Gyrase - genetics
Dose-Response Relationship, Drug
Drug Resistance, Bacterial - genetics
Drug Resistance, Multiple, Bacterial - genetics
Drug susceptibility testing
Fluoroquinolones
Fluoroquinolones - administration & dosage
Fluoroquinolones - pharmacology
Genotype
Humans
Level of resistance
Microbial Sensitivity Tests - methods
Mutation
Mutations
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Ofloxacin - administration & dosage
Ofloxacin - pharmacology
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Summary:To correlate gyrA mutations found on the Genotype MTBDRsl assay in Mycobacterium tuberculosis (MTB) isolates with Minimum Inhibitory Concentrations (MICs) to the fluoroquinolones compounds ofloxacin (OFX) and moxifloxacin (MXF). MICs for OFX and MXF were ascertained for 93 archived clinical MTB isolates that showed gyrA mutations at Ala90Val, Ser91Pro, Asp94Ala, Asn/Tyr, Gly and His. Thirty fluoroquinolones susceptible isolates as determined by presence of all wild-type gyrA bands on the Genotype MTBDRsl assay were also included. gyrA mutations at Ala90Val (n = 25), Ser91Pro (n = 6), Asp94Ala (n = 4), Asp94Asn/Tyr (n = 13), Asp94Gly (n = 42) and Asp94His (n = 3) were observed. Isolates with mutations at Ala90Val or Ser91Pro had MIC90 of 4.0 μg/ml and 1.0 μg/ml for OFX and MXF, respectively, and isolates with mutations at Asp 94Ala, Asn/Tyr, Gly and His had MIC90 of 8.0 μg/ml, and 2.5 μg/ml for OFX and MXF, respectively. MTB MICs were found to be consistently lower for MXF than for OFX among isolates with the same gyrA mutation (e.g. Ala90Val). The majority of MTB isolates containing mutations at Asp94Ala, Asn/Tyr, Gly and His in gyrA were associated with a moderate level of resistance to MXF (MIC = 2.5 μg/ml), although 3 isolates with the mutations Asp94Asn/Tyr/Gly were associated with a high level of resistance to both fluoroquinolones (MXF MICs = 5.0–8.0 μg/ml, OFX MICs = ≥10.0 μg/ml).
ISSN:1472-9792
1873-281X
DOI:10.1016/j.tube.2014.11.003