Table 6.

In vivo activities of TBG-MINO, DMG-DMDOT, and minocycline against experimental acute lethal infections in mice

Infection (resistance determinant or resistance; challenge dose [CFU/mouse])Intravenous treatmentED50(mg/kg) (95% confidence limit)MIC (μg/ml)
Staphylococcus aureus UBMS 90-2 (tet(M), ribosomal protection; 7.9 × 107)TBG-MINO1.0 (0.87–1.3)0.12
DMG-DMDOT0.68 (0.56–0.81)0.12
Minocycline1.8 (1.5–2.2)2.0
Staphylococcus aureus UBMS 88-7,649(pUB111) (tet(K), efflux; 9.0 × 107)TBG-MINO2.1 (1.8–2.6)0.5
DMG-DMDOT3.1 (2.5–3.7)1.0
Minocycline2.0 (1.6–2.4)0.25
Staphylococcus aureus NEMC 89-4 (MRSA; 5.3 × 107)TBG-MINO0.79 (0.64–0.97)0.50
DMG-DMDOT0.48 (0.39–0.59)0.25
Minocycline0.31 (0.25–0.38)0.12
Staphylococcus aureus ID 4729 (MRSA,tet(M); 1.3 × 108)TBG-MINO0.84 (0.69–1.0)0.5
DMG-DMDOT0.53 (0.43–0.64)0.25
Minocycline1.6 (1.3–2.0)4.0
Staphylococcus aureus ID 2371 (MRSA,tet(M), tet(K); 1.3 × 108)TBG-MINO2.3 (1.9–2.7)1.0
DMG-DMDOT3.0 (2.4–3.6)2.0
Minocycline16 (13–20)4.0
Streptococcus pneumoniae ATCC 6301 (penicillin susceptible; 3.3 × 101)TBG-MINO1.3 (1.1–1.6)0.12
DMG-DMDOT1.3 (1.1–1.6)0.06
Minocycline3.9 (3.2–4.8)0.12
Streptococcus pneumoniae ATCC 10015 (penicillin susceptible; 1.5 × 101)TBG-MINO1.7 (1.4–2.2)0.12
DMG-DMDOT1.9 (1.5–2.4)0.12
Minocycline3.5 (2.8–4.4)0.12
Streptococcus pneumoniae GS 1894 (penicillin resistant; 3.7 × 101)TBG-MINO0.61 (0.48–0.77)0.12
DMG-DMDOT0.53 (0.42–0.67)0.12
Minocycline20 (16–26)4
Escherichia coli 311 (susceptible; 2.3 × 106)TBG-MINO1.7 (1.4–2.1)0.5
DMG-DMDOT1.5 (1.2–1.8)0.5
Minocycline3.2 (2.6–4.0)1.0
Escherichia coli J3272 (pRP1) (tet(A), efflux; 1.6 × 107)TBG-MINO1.6 (1.0–2.6)0.5
DMG-DMDOT4.6 (2.9–7.5)2.0
Minocycline16.0 (9.8–26.0)4.0
Escherichia coli J3272(pBR322) (tet(C), efflux; 2.6 × 107)TBG-MINO1.5 (1.3–1.9)0.25
DMG-DMDOT5.0 (4.1–6.4)2.0
Minocycline14.0 (11.0–17.0)4.0
Escherichia coli UBMS 90-4 (tet(M), ribosomal protection; 6.6 × 107)TBG-MINO3.5 (2.8–4.3)0.25
DMG-DMDOT2.1 (1.8–2.6)0.25
Minocycline>32.0>32.0
Escherichia coli UBMS 88-1, J3272TcR (tet(B), efflux; 3.9 × 107)TBG-MINO3.9 (3.2–4.9)0.5
DMG-DMDOT3.1 (2.5–3.8)0.5
Minocycline>32.032.0
Escherichia coli NEMC 87-30 (minocycline resistant; 5.3 × 107)TBG-MINO1.6 (1.3–1.9)0.5
DMG-DMDOT2.0 (1.7–2.4)0.5
Minocycline>32.032.0
Organism (no. of isolates)AntibioticMIC (μg/ml)
Range50%90%
Moraxella catarrhalis(14)TBG-MINO0.12–0.250.120.25
DMG-MINO0.06–0.120.120.12
DMG-DMDOT0.12–0.250.120.25
Minocycline0.008–0.060.030.06
Tetracycline0.06–0.250.120.25
Ciprofloxacin0.03–0.060.030.06
Imipenem0.008–0.060.0150.06
Ceftazidime0.015–0.120.0150.06
Neisseria gonorrhoeae(22)TBG-MINO0.25–10.51
DMG-MINO0.12–10.250.5
DMG-DMDOT0.25–10.51
Minocycline0.25–>320.532
Tetracycline0.5–>321>32
Ciprofloxacin≤0.004≤0.004≤0.004
Imipenem0.015–0.120.060.12
Ceftazidime0.015–0.250.030.06
Haemophilus influenzae(15)TBG-MINO0.25–10.51
DMG-MINO0.25–0.50.250.5
DMG-DMDOT0.25–0.50.50.5
Minocycline0.12–0.250.120.25
Tetracycline0.12–80.250.5
Ciprofloxacin≤0.004–0.030.0150.03
Imipenem1–824
Ceftazidime0.015–0.250.120.12