USE OF A POLYENE MACROLIDE ANTIFUNGAL AGENT IN COMBINATION WITH A GLYCOPEPTIDE ANTIBACTERIAL AGENT

1 - 26 . (canceled)

27 . A pharmaceutical composition comprising:

(a) a polyene macrolide antifungal agent;

(b) a glycopeptide antibacterial agent having a substituent comprising at least about 8 carbon atoms; and

(c) a pharmaceutically acceptable carrier.

28 . The pharmaceutical composition according to claim 27 , wherein the polyene macrolide antifungal agent is amphotericin B, candidin, candidoin, candidinin, mycoheptin, nystatin, polyfungin, aureofacin, vacidin, trichomycin, candicidin or pimaricin; or a pharmaceutically acceptable salt thereof.

29 . The pharmaceutical composition according to claim 27 , wherein the glycopeptide antibacterial agent is selected from telavancin, oritavancin, dalbavancin and teicoplanin; or a pharmaceutically acceptable salt thereof.

30 . The pharmaceutical composition according to claim 27 , wherein the glycopeptide antibacterial agent is a compound of formula I:

wherein

X 1 and X 2 are independently hydrogen or chloro;

R 1 is selected from the group consisting of:

(a) —R a ;

(b) —C(O)—R b ;

(c) —R c —W 1 ;

(d) —C(O)—R d —W 2 ; and

(e) —R e —Y—R f ;

where

R a and R b are independently C 8-14 alkyl, C 8-14 alkenyl or C 8-14 alkynyl;

R c and R d are independently C 1-8 alkylene;

R e is C 2-8 alkylene;

R f is C 1-12 alkyl, C 2-12 alkenyl or C 2-12 alkynyl;

W 1 and W 2 are independently phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halo, -(phenyl), —CH 2 — (phenyl), —O-(phenyl), and

—O—CH 2 — (phenyl); wherein each -(phenyl) group is optionally substituted with 1 or 2 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy and halo;

Y is O, S or NH;

and provided that R 1 comprises at least 8 carbon atoms;

one of R 2 and R 3 is hydroxy and the other is hydrogen;

R 4 and R 5 are independently hydrogen or methyl;

R 6 is hydrogen or a group of formula (f):

R 7 is hydrogen or a group of formula (g):

n is an integer from 1 to 6;

or a pharmaceutically-acceptable salt thereof or stereoisomer thereof.

31 . The pharmaceutical composition according to claim 30 , wherein:

X 1 and X 2 are both chloro;

R 1 is —CH 2 CH 2 —NH—(CH 2 ) 9 CH 3 ;

R 2 is hydroxy;

R 3 is hydrogen;

R 4 is methyl;

R 5 is hydrogen;

R 6 is hydrogen; and

R 7 is —CH 2 —NH—CH 2 —P(O)(OH) 2 .

32 . The pharmaceutical composition according to any one of claims 29 , 30 and 31 , wherein the polyene macrolide antifungal agent is amphotericin B.

33 . A kit comprising:

(a) a polyene macrolide antifungal agent; and

(b) a glycopeptide antibacterial agent having a substituent comprising at least about 8 carbon atoms.

34 . The kit according to claim 33 , wherein the kit further comprises instructions for administering the polyene macrolide antifungal agent and the glycopeptide antibacterial agent to a subject.

35 . The kit according to claim 33 , wherein the polyene macrolide antifungal agent and the glycopeptide antibacterial agent are present as separate pharmaceutical compositions.

36 . The kit according to claim 33 , wherein the polyene macrolide antifungal agent and the glycopeptide antibacterial agent are present in a single pharmaceutical composition.

37 . The kit according to claim 33 , wherein the polyene macrolide antifungal agent is amphotericin B, candidin, candidoin, candidinin, mycoheptin, nystatin, polyfungin, aureofacin, vacidin, trichomycin, candicidin or pimaricin; or a pharmaceutically acceptable salt thereof.

38 . The kit according to claim 33 , wherein the glycopeptide antibacterial agent is selected from telavancin, oritavancin, dalbavancin and teicoplanin; or a pharmaceutically acceptable salt thereof.

39 . The kit according to claim 33 , wherein the glycopeptide antibacterial agent is a compound of formula I:

wherein

X 1 and X 2 are independently hydrogen or chloro;

R 1 is selected from the group consisting of:

(a) —R a ;

(b) —C(O)—R b ;

(c) —R c —W 1 ;

(d) —C(O)—R d —W 2 ; and

(e) —R e —Y—R f ;

where

R a and R b are independently C 8-14 alkyl, C 8-14 alkenyl or C 8-14 alkynyl;

R c and R d are independently C 1-8 alkylene;

R e is C 2-8 alkylene;

R f is C 1-12 alkyl, C 2-12 alkenyl or C 2-12 alkynyl;

W 1 and W 2 are independently phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halo, -(phenyl), —CH 2 — (phenyl), —O-(phenyl), and

—O—CH 2 — (phenyl); wherein each -(phenyl) group is optionally substituted with 1 or 2 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy and halo;

Y is O, S or NH;

and provided that R 1 comprises at least 8 carbon atoms;

one of R 2 and R 3 is hydroxy and the other is hydrogen;

R 4 and R 5 are independently hydrogen or methyl;

R 6 is hydrogen or a group of formula (f):

R 7 is hydrogen or a group of formula (g):

n is an integer from 1 to 6;

or a pharmaceutically-acceptable salt thereof or stereoisomer thereof.

40 . The kit according to claim 39 , wherein:

X 1 and X 2 are both chloro;

R 1 is —CH 2 CH 2 —NH—(CH 2 ) 9 CH 3 ;

R 2 is hydroxy;

R 3 is hydrogen;

R 4 is methyl;

R 5 is hydrogen;

R 6 is hydrogen; and

R 7 is —CH 2 —NH—CH 2 —P(O)(OH) 2 .

41 . The kit according to any one of claims 38 , 39 and 40 , wherein the polyene macrolide antifungal agent is amphotericin B.

42 . A system for treating a fungal infection in a subject, the system comprising:

(a) a polyene macrolide antifungal agent; and

(b) a glycopeptide antibacterial agent having a substituent comprising at least about 8 carbon atoms.

43 . The system according to claim 42 , wherein the polyene macrolide antifungal agent is amphotericin B, candidin, candidoin, candidinin, mycoheptin, nystatin, polyfungin, aureofacin, vacidin, trichomycin, candicidin or pimaricin; or a pharmaceutically acceptable salt thereof.

44 . The system according to claim 42 , wherein the glycopeptide antibacterial agent is selected from telavancin, oritavancin, dalbavancin and teicoplanin; or a pharmaceutically acceptable salt thereof.

45 . The system according to claim 42 , wherein the glycopeptide antibacterial agent is a compound of formula I:

wherein

X 1 and X 2 are independently hydrogen or chloro;

R 1 is selected from the group consisting of:

(a) —R a ;

(b) —C(O)—R b ;

(c) —R c —W 1 ;

(d) —C(O)—R d —W 2 ; and

(e) —R e —Y—R f ;

where

R a and R b are independently C 8-14 alkyl, C 8-14 alkenyl or C 8-14 alkynyl;

R c and R d are independently C 1-8 alkylene;

R e is C 2-8 alkylene;

R f is C 1-12 alkyl, C 2-12 alkenyl or C 2-12 alkynyl;

W 1 and W 2 are independently phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halo, -(phenyl), —CH 2 — (phenyl), —O-(phenyl), and

—O—CH 2 — (phenyl); wherein each -(phenyl) group is optionally substituted with 1 or 2 substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy and halo;

Y is O, S or NH;

and provided that R 1 comprises at least 8 carbon atoms;

one of R 2 and R 3 is hydroxy and the other is hydrogen;

R 4 and R 5 are independently hydrogen or methyl;

R 6 is hydrogen or a group of formula (f):

R 7 is hydrogen or a group of formula (g):

n is an integer from 1 to 6;

or a pharmaceutically-acceptable salt thereof or stereoisomer thereof.

46 . The system according to claim 45 , wherein:

X 1 and X 2 are both chloro;

R 1 is —CH 2 CH 2 —NH—(CH 2 ) 9 CH 3 ;

R 2 is hydroxy;

R 3 is hydrogen;

R 4 is methyl;

R 5 is hydrogen;

R 6 is hydrogen; and

R 7 is —CH 2 —NH—CH 2 —P(O)(OH) 2 .

47 . The system according to any one of claims 44 , 45 and 46 , wherein the polyene macrolide antifungal agent is amphotericin B.