The present disclosure is directed to lysin-AMP polypeptide constructs, isolated lysin polypeptides, and pharmaceutical compositions comprising the isolated polypeptides and/or lysin-AMP polypeptide constructs. Methods of using the lysin-AMP polypeptide constructs, isolated lysin polypeptides and pharmaceutical compositions are also herein provided, including methods of treating a bacterial infection of an organ or tissue in which pulmonary surfactant is present or Gram-negative bacterial infections that are associated with a biofilm. In addition, isolated polynucleotides encoding the lysin-AMP polypeptide constructs and isolated lysin polypeptides are disclosed herein.

The present invention provides compositions comprising as an essential feature granulocyte-macrophage colony-stimulating factor (GM-CSF) together with fosfomycin for the treatment of bacterial lung infections by administration via the air-ways.

The present invention provides compositions comprising as an essential feature granulocyte-macrophage colony-stimulating factor (GM-CSF) together with fosfomycin for the treatment of bacterial lung infections by administration via the air-ways.

The present invention provides compositions comprising as an essential feature granulocyte-macrophage colony-stimulating factor (GM-CSF) together with fosfomycin for the treatment of bacterial lung infections by administration via the air-ways.

The field of the present invention is that of fosfomycin formulations for parenteral administration, in particular for intravenous administration. Formulations of the prior art provide fosfomycin as a powder to be diluted directly prior to the administration. The aim of the invention is to provide a fosfomycin formulation for parenteral administration which is easier to produce and administer or which lowers the risk of puncture injuries for healthcare professionals and the health risks for the patients (for example due to contamination or incorrect dosages) by preventing additional processing steps. During the course of the invention, it was surprisingly shown that fosfomycin is much more stable in an aqueous solution than what is commonly assumed. The invention therefore provides a closed container which contains an aqueous solution for parenteral administration, wherein at least one pharmaceutically acceptable salt of fosfomycin, in particular fosfomycin disodium salt, and a pharmaceutically acceptable acid, in particular succinic acid, are dissolved in the solution. Preferred containers are breakable ampoules made of plastic or glass, puncturable vials, infusion bags, or syringes ready for injection.

The field of the present invention is that of fosfomycin formulations for parenteral administration, in particular for intravenous administration. Formulations of the prior art provide fosfomycin as a powder to be diluted directly prior to the administration. The aim of the invention is to provide a fosfomycin formulation for parenteral administration which is easier to produce and administer or which lowers the risk of puncture injuries for healthcare professionals and the health risks for the patients (for example due to contamination or incorrect dosages) by preventing additional processing steps. During the course of the invention, it was surprisingly shown that fosfomycin is much more stable in an aqueous solution than what is commonly assumed. The invention therefore provides a closed container which contains an aqueous solution for parenteral administration, wherein at least one pharmaceutically acceptable salt of fosfomycin, in particular fosfomycin disodium salt, and a pharmaceutically acceptable acid, in particular succinic acid, are dissolved in the solution. Preferred containers are breakable ampoules made of plastic or glass, puncturable vials, infusion bags, or syringes ready for injection.

There is provided a nanocomplex having a core-shell structure. The shell of the nanocomplex comprises a functionalized hyaluronic acid while the core of the nanocomplex comprises a flavonoid encapsulating a metal-containing compound. Preferably, the flavonoid is epigallocatechin gallate (EGCG) and the hyaluronic acid is thiol-functionalized and subsequently conjugated to the flavonoid. There is also provided a method of forming the nanocomplex, a pharmaceutical composition comprising the nanocomplex, medical uses of the nanocomplex and a method of treating a patient, preferably with cancer using the nanocomplex.

There is provided a nanocomplex having a core-shell structure. The shell of the nanocomplex comprises a functionalized hyaluronic acid while the core of the nanocomplex comprises a flavonoid encapsulating a metal-containing compound. Preferably, the flavonoid is epigallocatechin gallate (EGCG) and the hyaluronic acid is thiol-functionalized and subsequently conjugated to the flavonoid. There is also provided a method of forming the nanocomplex, a pharmaceutical composition comprising the nanocomplex, medical uses of the nanocomplex and a method of treating a patient, preferably with cancer using the nanocomplex.

Compounds, pharmaceutical compositions, and methods for reversing fosfomycin resistance are disclosed. Embodiments of the disclosed compounds inhibit fosfomycin-inhibiting enzymes. Some embodiments of the compounds are FosA inhibitors. The disclosed pharmaceutical compositions include (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) a compound, or a pharmaceutically acceptable salt thereof, which inhibits a fosfomycin-inhibiting enzyme. A method of inhibiting growth of a fosfomycin-resistant bacterium includes contacting the bacterium with (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof.

Compounds, pharmaceutical compositions, and methods for reversing fosfomycin resistance are disclosed. Embodiments of the disclosed compounds inhibit fosfomycin-inhibiting enzymes. Some embodiments of the compounds are FosA inhibitors. The disclosed pharmaceutical compositions include (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) a compound, or a pharmaceutically acceptable salt thereof, which inhibits a fosfomycin-inhibiting enzyme. A method of inhibiting growth of a fosfomycin-resistant bacterium includes contacting the bacterium with (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof.