Emergence of Fluoroquinolone Resistance in Mycobacterium tuberculosis during Continuously Dosed Moxifloxacin Monotherapy in a Mouse Model (original) (raw)
2005, Antimicrobial Agents and Chemotherapy
https://doi.org/10.1128/AAC.49.9.3977-3979.2005
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Abstract
Fluoroquinolone resistance in tuberculosis may rapidly emerge. Mice infected with high titers of aerosolized Mycobacterium tuberculosis and treated for 8 weeks with four concentrations of moxifloxacin (0.125, 0.25, 0.50, and 1.0%) mixed into the diet had drug concentrations of 2.4, 4.1, 5.3, and 17.9 g/ml, respectively, in blood. Selection of fluoroquinolone-resistant mutants occurred in all surviving mice.
Figures (4)
TABLE 1. gyrA and gyrB QRDR mutations of in vitro isolates of M. tuberculosis H37Rv grown on plates containing MXF (1, 2, and 4 pg/ml)
TABLE 2. Mouse weights before and after initiation of MXF mixed into the diet
“ C, contaminated; **, on replating of frozen lung homogenates, MXF-resistant M. tuberculosis isolates were recovered; ***, on replating of frozen lung homogenates, MXF-resistant M. tuberculosis isolates were not recovered. > Number of CFU/lung. © When the frozen lung homogenate from mouse 1 in the group receiving 0.5% MXF mixed in the diet was replated, the number of CFU/lung was 1.34 x 10° and there was one MXF-resistant mutant, for a prevalence of 7.5 X 107°. TABLE 3. Number and percentage of colonies isolated on control and MXF-containing plates after 8 weeks’ treatmer
“Treatment group 5 and 6 MXF-resistant colonies were grown from day 56 frozen lung homogenates. > NA, not applicable. TABLE 4. Determination of mutation in QRDRs of gyrA and gyrB of MXF-resistant colonies grown from day 56 lung homogenates
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Clinical Epidemiology and Global Health
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