Treatment of infections

A method of preventing or treating a joint infection in a patient, the method comprising the step of administering a pharmaceutically effective amount of a conjugate or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt, wherein said conjugate is water-insoluble and comprises a polymeric moiety-Z, which is a hyaluronic acid-based or PEG-based hydrogel, to which a plurality of moieties -L2-X0D-L1-D are covalently conjugated,

• wherein
• each -D is independently an antibiotic moiety;
• each -L1- is independently of formula (II):
• wherein the dashed line indicates the attachment to a nitrogen, hydroxyl or thiol of -D;
• —X— is selected from the group consisting of —C(R4R4a)—, —N(R4)—, —O—, —C(R4R4a)—C(R5R5a)—, —C(R5R5a)—C(R4R4a)—, —C(R4R4a)—N(R6)—, —N(R6)—C(R4R4a)—, —C(R4R4a)—O—, —O—C(R4R4a)—, and —C(R7R7a)—;
• X1 is selected from the group consisting of C and S (O);
• —X2— is selected from the group consisting of —C(R8R8a)— and —C(R8R8a)—C(R9R9a)—;
• ═X3 is selected from the group consisting of ═O, ═S, and ═N—CN;
• —R1, —R1a, —R2, —R2a, —R4, —R4a, —R5, —R5a, —R6, —R8, —R8a, —R9 and —R9a are independently selected from the group consisting of —H and C1-6 alkyl;
• —R3 and —R3a are independently selected from the group consisting of —H and C1-6 alkyl, provided that in case one of —R3 and —R3a or both are other than —H, they are connected to the nitrogen atom to which they are attached through an sp3-hybridized carbon atom;
• —R7 is selected from the group consisting of —N(R10R10a) and —NR10—(C═O)—R11;
• —R7a, —R10, —R10a and —R11 are independently of each other selected from the group consisting of —H and C1-6 alkyl;
• alternatively, one or more of the pairs-R1a/—R4a, —R1a/—R5a, —R1a/—R7a, —R4a/—R5a and —R8a/—R9a form a chemical bond;
• alternatively, one or more of the pairs-R1/—R1a, —R2/—R2a, —R4/—R4a, —R5/—R5a, —R8/—R8a and —R9/—R9a are joined together with the atom to which they are attached to form a C3-10 cycloalkyl or 3- to 10-membered heterocyclyl;
• alternatively, one or more of the pairs-R1/—R4, —R1/—R5, —R1/—R6, —R1/—R7a, —R4/—R5, —R4/—R6, —R8/—R9 and —R2/—R3 are joined together with the atoms to which they are attached to form a ring A;
• alternatively, —R3/—R3a are joined together with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycle;
• A is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl;
• and
• wherein -L1- is substituted with —X0D-L2- and wherein -L1- is optionally further substituted, provided that the hydrogen marked with the asterisk in formula (II) is not replaced by —X0D-L2-or a substituent;
• each —X0D— is independently absent or a linkage;
• each -L2- is independently absent or a spacer moiety;
• the conjugate is a pre-synthesized conjugate;
• and
• wherein the method of preventing or treating a joint infection also comprises the step of preventing the formation of a biofilm or eradicating an existing biofilm in said patient.