Substituted polyamines as inhibitors of bacterial efflux pumps

A method for treating a microbial infection in an animal, comprising administering to an animal suffering from said infection an efflux pump inhibitor in an amount sufficient to reduce efflux pump activity, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group, such that infection is inhibited.

A method of treating an infection caused by a microbe in a subject comprising administering an inhibitor of an efflux pump to the subject such that the infection is treated, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group, such that said infection is treated.

A method of enhancing the antimicrobial activity of an antimicrobial agent against a microbe, comprising contacting said microbe with said antimicrobial agent and an efflux pump inhibitor in an amount effective to inhibit an efflux pump in said microbe, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group, such that said activity is enhanced.

A method of enhancing the antimicrobial activity of a drug comprising contacting a microbe that is resistant to one or more drugs with a drug to which the microbe is resistant and an inhibitor of an efflux pump to thereby enhance the antimicrobial activity of a drug, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group, such that said antimicrobial activity is enhanced.

A pharmaceutical composition effective for treatment of an infection of an animal by a microbe, comprising an efflux pump inhibitor and a pharmaceutically acceptable carrier, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group.

A composition comprising a non-antibiotic bactericidal or bacteriostatic first agent and a second agent that inhibits the expression or activity of an efflux pump, wherein said inhibitor is a polyazaalkane, polyaminoalkane, or mixed poly(aza/amino)alkane, any carbon atom of which may be hydroxyl, amino, or oxo substituted, and wherein said inhibitor contains at least two nitrogen atoms that are bonded to a lipophilic group.

A pharmaceutical composition comprising an antibiotic and an inhibitor of an efflux pump selected from the group consisting of N-benzylated polyazaalkanes, N-benzylated polyaminoalkanes, or mixed N-benzylated poly(aza/amino)alkanes, any carbon atom of which may be hydroxyl, amino, or oxo substituted.