The Journal of antimicrobial chemotherapy
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J. Antimicrob. Chemother. · Dec 2016
In vivo Mycobacterium tuberculosis fluoroquinolone resistance emergence: a complex phenomenon poorly detected by current diagnostic tests.
Heteroresistance, described both in terms of various point mutations resulting in different levels of resistance and in terms of a mixture of mutant and WT bacilli, is identified in up to one-third of fluoroquinolone (FQ)-resistant Mycobacterium tuberculosis isolates. Heteroresistance is a challenge for current phenotypic and genotypic susceptibility testing (DST) regimes. We aimed to compare the performances of different phenotypic and genotypic DST in the context of FQ heteroresistance by mimicking, in a murine model, the course of selection of FQ resistance during treatment. ⋯ Our study shows the in vivo complexity of FQ resistance emergence and the poor sensitivity of Sanger DNA sequencing for detection of heteroresistance. Our data support the use of 0.5 mg/L moxifloxacin in LJ for detection of FQ resistance, but not the recent increase in the ofloxacin critical concentration from 2 to 4 mg/L given in the WHO recommendations.