Reducing tetracycline resistance in living cells

A method for converting tetracycline resistant bacteria into tetracycline sensitive bacteria, comprising contacting the resistant bacteria with a predetermined quantity of at least a first composition selected from C5 esters of tetracycline, 13,5 derivative or 6-deoxy-13-(substituted mercapto)tetracyclines, and concomitantly administering to the cell a predetermined quantity of at least a second composition selected from a tetracycline, a tetracycline analogue or a tetracycline derivative which is not a C5 ester of tetracycline nor a 6-deoxy-13-(substituted mercapto)tetracycline.

A pharmaceutical preparation for converting tetracycline resistant bacteria into tetracycline sensitive bacteria comprising a blocking agent which is capable of interacting with a product of at least one tetracycline resistance determinant capable of protecting ribosomes in the cell from the inhibitory activity of tetracycline, a tetracycline type antibiotic, and a pharmaceutical carrier.

A pharmaceutical preparation for converting tetracycline resistant bacteria into tetracycline sensitive bacteria comprising a 6-deoxy-13(substituted mercapto)tetracycline, a tetracycline-type antibiotic which is not a 6-deoxy-13-(substituted mercapto)-tetracycline, and a pharmaceutically acceptable carrier.

A pharmaceutical preparation for converting tetracycline resistant bacteria into tetracycline sensitive bacteria comprising a C5 ester of tetracycline, a tetracycline-type antibiotic which is not a C5 ester of tetracycline, and a pharmaceutically acceptable carrier.

A pharmaceutical preparation for converting tetracycline resistant bacteria into tetracycline sensitive bacteria comprising a 13,5 derivative of tetracycline, a tetracycline-type antibiotic which is not a 13,5 derivative of tetracycline, and a pharmaceutically acceptable carrier.

A class of C5 esters of tetracycline compositions useful in combination with other classes of tetracyclines, tetracycline analogues and tetracycline derivatives, said class of compositions having the formula ##STR48## wherein R1 and R2 are selected from the group consisting of a methylene group, hydroxyl, hydrogen or a group consisting of organic entities comprising from 1-12 carbon atoms, with or without other heteroatoms including sulfur, oxygen, halogen, nitrogen, and the like, and takes form as linear, branched, or cyclic alkyl, aryl, or alkylaryl structures;

• and A is selected from the group consisting of a hydrogen atom, a methylene group, and any linear, branched, or ring structure comprising from 1-6 carbon atoms and optionally including heteroatoms such as oxygen and nitrogen atoms.

A class of 6-deoxy-13-(substituted mercapto) tetracyline compositions useful in the therapeutic treatment of a tetracycline resistant cell in combination with other classes of tetracyclines, tetracycline analogues and tetracycline derivatives, said class of compositions having the formula ##STR49## wherein A is hydrogen or hydroxyl, B comprises a morpholino group, and

• R is an organic entity comprising 1-12 carbon atoms and optionally including heteratoms.