# US 12,594,289 B2 · Potentiation of antibiotic effect > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,594,289 B2 - Document ID: US12594289B2 - Status: Granted - Kind: B2 - Application number: 18/448,538 - Filed: 2023-08-11 - Published: 2023-11-30 - Granted: 2026-04-07 - Earliest claimed: 2017-07-19 - Assignees: The University of North Carolina at Chapel Hill - Applicants: The University of North Carolina at Chapel Hill - Inventors: Brian Conlon; Sarah Conlon; Lauren Radlinski - Web page: https://patentgrep.com/patent/US12594289B2 ## CPC - A61K 31/702: Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 31/7028: Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages - A61K 31/7036: having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins - A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 31/04: Antibacterial agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to compositions, kits and methods using combinations of surfactants or cell wall-hydrolyzing enzymes with antibiotics to potentiate the antibiotic effect against bacterial infections. In some embodiments, the surfactant is a pore-forming biosurfactant such as rhamnolipids and the antibiotic is an aminoglycoside antibiotic such as tobramycin. ## Claims ### Claim 1 A method of treating a bacterial infection comprising a biofilm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein: (a) the surfactant consists of palmitoleic acid; (b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof; (c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the minimum inhibitory concentration (MIC) of the aminoglycoside antibiotic or vancomycin; wherein the bacterial infection comprising a biofilm is caused by gram-positive bacteria; and wherein the bacterial infection comprising a biofilm is treated. ### Claim 2 A method of reducing the risk of recurrence of a bacterial infection in a subject in need thereof, comprising administering to the subject having a bacterial infection comprising a biofilm a therapeutically effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein: (a) the surfactant consists of palmitoleic acid; (b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof; (c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the MIC of the aminoglycoside antibiotic or vancomycin; wherein the bacterial infection comprising a biofilm is caused by a gram-positive bacteria; and wherein the risk of recurrence of a bacterial infection is reduced. ### Claim 3 A method of disrupting a biofilm, comprising contacting the biofilm with an effective amount of a surfactant and at least one of an aminoglycoside antibiotic or vancomycin, wherein: (a) the surfactant consists of palmitoleic acid; (b) the aminoglycoside antibiotic comprises streptomycin, kanamycin A, amikacin, dibekacin, sisomicin, netilmicin, neomycin B, neomycin C, neomycin E, or any combination thereof; (c) the surfactant synergizes with the aminoglycoside antibiotic or vancomycin to decrease the MIC of the aminoglycoside antibiotic or vancomycin; wherein the biofilm is from a gram-positive bacteria; and wherein the biofilm is disrupted. ### Claim 4 (depends on 1) The method of claim 1, wherein the bacteria is antibiotic resistant or antibiotic tolerant. ### Claim 5 (depends on 1) The method of claim 1, wherein the bacteria is Staphylococcus aureus. ### Claim 6 (depends on 5) The method of claim 5, wherein the bacteria is methicillin-resistant Staphylococcus aureus. ### Claim 7 (depends on 1) The method of claim 1, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously. ### Claim 8 (depends on 1) The method of claim 1, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially. ### Claim 9 (depends on 2) The method of claim 2, wherein the bacteria is antibiotic resistant or antibiotic tolerant. ### Claim 10 (depends on 2) The method of claim 2, wherein the bacteria is Staphylococcus aureus. ### Claim 11 (depends on 10) The method of claim 10, wherein the bacteria is methicillin-resistant Staphylococcus aureus. ### Claim 12 (depends on 2) The method of claim 2, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously. ### Claim 13 (depends on 2) The method of claim 2, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially. ### Claim 14 (depends on 3) The method of claim 3, wherein the bacteria is antibiotic resistant or antibiotic tolerant. ### Claim 15 (depends on 3) The method of claim 3, wherein the bacteria is Staphylococcus aureus. ### Claim 16 (depends on 15) The method of claim 15, wherein the bacteria is methicillin-resistant Staphylococcus aureus. ### Claim 17 (depends on 3) The method of claim 3, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered simultaneously. ### Claim 18 (depends on 3) The method of claim 3, wherein the surfactant and the aminoglycoside antibiotic or vancomycin are administered sequentially.