Streptomycin tolerances

Gentamicin should be added if tolerance or moderately susceptible (MIC >0.1 g/mL) organisms are encountered streptomycin is used but can be more toxic. 

Drugs of choice are isoniazid, rifampin, ethambutol, along with streptomycin and pyrazinamide. Less well tolerated, second-line agents include p-aminosal-icylic acid, cycloserine, viomycin, ka-namycin, amikacin, capreomycin, ethionamide. 

Although no analogs of streptomycin exist in which the C5 position is altered, the structure of the complex suggests that very few, if any, modifications would be tolerated, because that hydroxyl group is also involved in a hydrogen bond with Lys45 of SI2. Similar restrictions are not expected for C2 modification, as there are no direct contacts between its hydroxyl group and the ribosome. 

Several active natural streptomycin analogs, such as 5 -hydroxystreptomycin and AC4437, are hydroxylated at C5 (34, 52). Semisynthetic derivatives of this position are absent. A cursory inspection of the streptomy-cin/30S structure suggests that the methyl group at C4 contributes little to ribosome binding, suggesting that modifications at this position might be tolerated. 

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