A pyrimidine derivative represented by formula (I) Or optical isomers, racemic mixtures thereof, pharmaceutically acceptable acid addition salts, pharmaceutically acceptable metal salts, or alkylated ammonium salts thereof; for use together with a membrane penetrating agent in a treatment or prevention of Gram-negative bacterial infection in a host mammal in need of such treatment or prevention, wherein: X 1 and X 2 are independently N, CH, CR 8 wherein R 8 is C 1-6 alkyl, C 2 - 6 alkenyl or C 2 - 6 alkynyl; with the exception that if one of X 1 or X 2 is equal to N, then the remaining of X 1 or X 2 are selected from CH, CR 8 ; -Y- is -O- or -S-; R 1 and R 2 are independently C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-6 -cycloalkyl, aryl, aryl-C 1-6 -alkyl wherein the alkyl or cycloalkyl moiety is optionally mono or polysubstituted with OH or an halogen and the aryl moiety is optionally mono or polysubstituted with an halogen, -C 1-6 alkyl, - C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , - SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 ; R 3 , R 4 , R 5 , R 6 and R 7 are independently H, an halogen, a C 1-6 alkyl, C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , -SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 . Or optical isomers, racemic mixtures thereof, pharmaceutically acceptable acid addition salts, pharmaceutically acceptable metal salts, or alkylated ammonium salts thereof; for use together with a membrane penetrating agent in a treatment or prevention of Gram-negative bacterial infection in a host mammal in need of such treatment or prevention, wherein: X 1 and X 2 are independently N, CH, CR 8 wherein R 8 is C 1-6 alkyl, C 2 - 6 alkenyl or C 2 - 6 alkynyl; with the exception that if one of X 1 or X 2 is equal to N, then the remaining of X 1 or X 2 are selected from CH, CR 8 ; -Y- is -O- or -S-; R 1 and R 2 are independently C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-6 -cycloalkyl, aryl, aryl-C 1-6 -alkyl wherein the alkyl or cycloalkyl moiety is optionally mono or polysubstituted with OH or an halogen and the aryl moiety is optionally mono or polysubstituted with an halogen, -C 1-6 alkyl, - C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , - SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 ; R 3 , R 4 , R 5 , R 6 and R 7 are independently H, an halogen, a C 1-6 alkyl, C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , -SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 . X 1 and X 2 are independently N, CH, CR 8 wherein R 8 is C 1-6 alkyl, C 2 - 6 alkenyl or C 2 - 6 alkynyl; with the exception that if one of X 1 or X 2 is equal to N, then the remaining of X 1 or X 2 are selected from CH, CR 8 ; -Y- is -O- or -S-; R 1 and R 2 are independently C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-6 -cycloalkyl, aryl, aryl-C 1-6 -alkyl wherein the alkyl or cycloalkyl moiety is optionally mono or polysubstituted with OH or an halogen and the aryl moiety is optionally mono or polysubstituted with an halogen, -C 1-6 alkyl, - C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , - SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 ; R 3 , R 4 , R 5 , R 6 and R 7 are independently H, an halogen, a C 1-6 alkyl, C 1-6 alkoxy, -OH, -NO 2 , -CN, -NH 2 , -NHR 8 , -N(R 8 ) 2 -COOH, -COOR 8 , -CONH 2 , -CONHR 8 , -CON(R 8 ) 2 , -SO 2 NH 2 , -SO 2 NHR 8 , or -SO 2 N(R 8 ) 2 . <EOS>