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Cross-resistance between aminoglycosides (e.g. streptomycin, kanamycin, amikacin) and polypeptides (e.g. capreomycin) is complex. Perhaps as a simplified rule one could state that it is most efficient to use first streptomycin because if there is streptomycin resistance the likelihood that any of the other aminoglycosides or the polypeptides remain efficacious is larger than if the sequence is inverted. While there are likely important differences between different settings, this study from Gerogia in the caucasus, would suggest that the second injectable drug that could be used in the presence of streptomycin is kanamycin because if there is also resistance acquired to kanamycin, the chances are better that any of the two remaining (amikacin, capreomycin) still work than if any other sequence were chosen.

The concept of the sequential approach with regimens, also holds for the sequential approach with a drug class, the preferred approach is to always keep the door open for a fallbak option.