Immunodeficiency and Intermittent Dosing Promote Acquired Rifamycin Monoresistance in Murine Tuberculosis

↵a Drug doses (in mg/kg) if not otherwise specified: rifampin (R), 10; rifapentine (P), 10; isoniazid (H), 10; pyrazinamide (Z), 150; ethambutol (E), 100. The mortality data include only mice dead from any cause before scheduled sacrifice or sacrificed earlier due to severe illness.

↵b Numbers within parentheses indicate the proportions of dying mice harboring ≥1% resistant CFU. ?, not assessable.

↵a Selective amplification defined by 0.01 < H < 1% or 0.001 < R < 1% of resistance on H (0.2 μg/ml) or R (1.0 μg/ml).

↵b Resistance defined by resistant CFU comprising ≥1% of total CFU.

↵c One isolate was multidrug resistant (MDR) which was resistant to both H (0.2 μg/ml) and R (1.0 μg/ml).

↵d One isolate had heterogenous strains which were resistant to either H (0.2 μg/ml) or R (1.0 μg/ml) but not both.

↵a Drug doses (in mg/kg) if not otherwise specified: rifampin (R), 10; rifapentine (P), 10; isoniazid (H), 10; pyrazinamide (Z), 150; ethambutol (E), 100. (2 + 6)w, combination of 2-week plus 6-week drug administration; G, group; ins, insertion; del, deletion; WT, wild type.

↵b Resistance defined by growth on H (0.2 μg/ml) or R (1 μg/ml).

↵c MIC measured only with resistant isolates on H (0.2 μg/ml) or R (1 μg/ml).