Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure

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Abstract
We assessed the fluoroquinolone (FQ) susceptibility of clinical isolates of Mycobacterium tuberculosis in an endemic area. The genetic mutations responsible for FQ resistance were also evaluated. A total of 420 M. tuberculosis isolates during January 2004 to December 2005 were randomly selected. Data on the clinical characteristics of the patients were obtained from medical records. The MICs of ofloxacin, ciprofloxacin, levofloxacin and moxifloxacin were determined. Spoligotyping and sequencing of the gyrA and gyrB genes were performed for all isolates resistant to any tested FQ. Of the 420 isolates, 52 (12.4%), 26 (6.2%), 26 (6.2%) and 30 (7.1%) were resistant to isoniazid, rifampicin, ethambutol and streptomycin, respectively. Multidrug resistance was found in 5.0% of isolates. For all tested FQs, the susceptibility rate was higher than 97%. Resistance to any first-line drug and isolation from a patient with prior anti-tuberculous treatment were correlated with FQ resistance. Multidrug resistance had the strongest correlation with FQ resistance (19% of isolates). Neither the previous use of FQs nor the duration of FQ exposure was correlated with the FQ susceptibility. Of the 14 FQ-resistant isolates, five (35.7%) had gyrA mutations (four D94G and one A90V) and another one (7.1%) had a gyrB mutation (N538D). This study found FQ resistance in 3.3% of all clinical isolates of M. tuberculosis. FQ resistance was correlated with first-line drug resistance and prior anti-tuberculous treatment, suggesting the need for routine FQ susceptibility testing in patients with these characteristics.