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

Summary Objective To correlate gyrA mutations found on the Genotype MTBDR sl assay in Mycobacterium tuberculosis ( MTB ) isolates with Minimum Inhibitory Concentrations (MICs) to the fluoroquinolones compounds ofloxacin (OFX) and moxifloxacin (MXF). Methods 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 MTBDR sl assay were also included. Results 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 MIC 90 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 MIC 90 of 8.0 μg/ml, and 2.5 μg/ml for OFX and MXF, respectively. Conclusions 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).