title: Correlating Minimum Inhibitory Concentrations of ofloxacin and moxifloxacin with gyrA mutations using the genotype MTBDRsl assay.
abstract: OBJECTIVE
  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).
  
  
  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 MTBDRsl 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 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.
  
  
  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).
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Priti
authors.initials: P
authors.lastname: Kambli
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Ajbani
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Meeta
authors.initials: M
authors.lastname: Sadani
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Chaitali
authors.initials: C
authors.lastname: Nikam
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Section Pulmonology, Department of Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
authors.forename: Zarir
authors.initials: Z
authors.lastname: Udwadia
authors.affiliation: University of California, San Diego, Department of Medicine, San Diego, CA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Rodwell
authors.affiliation: University of California, San Diego, Department of Medicine, San Diego, CA, USA.
authors.forename: Antonino
authors.initials: A
authors.lastname: Catanzaro
authors.affiliation: Section Microbiology, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India. Electronic address: dr_crodrigues@hindujahospital.com.
authors.forename: Camilla
authors.initials: C
authors.lastname: Rodrigues
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D000077266:Moxifloxacin; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015242:Ofloxacin; D027081:DNA Gyrase; D000077266:Moxifloxacin
keywords: Drug susceptibility testing; Fluoroquinolones; Level of resistance; Mutations