%0 Journal Article %A Claire Andrejak %A Sandeep Tyagi %A Eric Nuermberger %A Jacques Grosset %T Can streptomycin prevent the selection of isoniazid-resistant mutants in nude mice infected with M. tuberculosis? %D 2011 %J European Respiratory Journal %P p856 %V 38 %N Suppl 55 %X Rationale: In a previous study, the treatment of M.tuberculosis infected athymic nu/nu (nude) mice with the bactericidal drug isoniazid (H) combined with the two sterilizing drugs, rifampicin (R) and pyrazinamide (Z) failed and selected H-resistant mutants. We investigated whether the combination of H with the bactericidal drug, streptomycin (S) would be able to prevent that selection.Methods: A total of 80 nude mice were aerosol infected with 3.67±0.13 log10 of M. tuberculosis H37Rv. Two weeks later, at treatment initiation, mice were randomized in the following subgroups: untreated and treated with RZH + ethambutol (E) as controls; treated with SH or RH, as tests, Treatment was given five days/week for 12 weeks. Drug doses (mg/kg) were 10 for R and H, 150 for Z and 100 for S and E. Lung CFU counts were done the day after infection, on treatment initiation, and after 4, 8 and 12 weeks of treatment on plain and H 0.2 μg/ml-containing 7H11 selective plates.Results: Lung CFU counts were 7.40±0.28 log10 on treatment initiation. After 4, 8 and 12 weeks of treatment, they were 5.82±0.35, 4.05±0.55 and 2.30±0.25, respectively for RHZE; 5.00±0.09, 5.32±0.6 and 6.57±0.29, respectively for SH; and 6.00±0.39, 6.24±0.28, 7.68±0.49, respectively for RH. H resistance was prevented in RHZE treated mice but not in SH and RH treated mice.Conclusion: Despite its bactericidal activity, S alone cannot prevent selection of H-resistant mutants in nude mice. %U