TABLE 4

MIC and mutational analysis of isolates harboring >1% resistancea

Treatment group and regimenDuration of treatment (wks)Resistant CFUb (%)MIC (μg/ml)katG mutationrpoB mutation
HRHRNucleotideAmino acidNucleotideAmino acid
BALB/c mice
    G2, P 5/716097 >16 1592 C→TS531L
24077 >16 1576 C→TH526Y
Nude
    G2, P 5/74<0.012 >16 1577 A→GH526R
13<0.01100 >16 1576 C→TH526Y
13<0.012 2–4 1598 T→CL533P
130100 >16 1576 C→TH526Y
13<0.0120 >16 1577 A→GH526R
1606 >16 1565 C→TS522L
    G7, (2 + 6)wRHZE + 4P 1/716<0.013 >16 1592 C→GS531W
160.060.25>16c>16c1513 T→CW505R1592 C→TS531L
24<0.016 >16 1576 C→TH526Y
    G8, (2 + 6)wRHZE + 4PH50 1/716330>16 765 G→CM255I
161000>16 691 A insFrame shift
240100 >16 1592 C→TS531L
    G9, (2 + 6)wRHZE + 4P15H50 1/7161000>16 902 AG delFrame shift
16750>16 WT
    G11, (2 + 6)wRH5ZE + 4RH12.5 2/7191000.0014>16 853 G insFrame shift
    G13, (2 + 6)wRH5ZE + 4PH25 1/7160100 >16 1592 C→TS531L
    G14, (2 + 6)wRH5ZE + 4P15H25 1/716160>16 1856 T→GL619R
241000>16 1643 G→AG548D
    G15, (2 + 6)wRH5ZE + 4P20H25 1/716300>16 WT
160100 >16 1592 C→TS531L
  • 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).