WO2019036770A1 - Compositions antimicrobiennes et procédés d'utilisation - Google Patents

Compositions antimicrobiennes et procédés d'utilisation Download PDF

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WO2019036770A1
WO2019036770A1 PCT/AU2018/050907 AU2018050907W WO2019036770A1 WO 2019036770 A1 WO2019036770 A1 WO 2019036770A1 AU 2018050907 W AU2018050907 W AU 2018050907W WO 2019036770 A1 WO2019036770 A1 WO 2019036770A1
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glycerolipid
composition
subject
infection
content
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PCT/AU2018/050907
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English (en)
Inventor
Nicky Dieter THOMAS
Katharina Richter
Clive Allan Prestidge
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University Of South Australia
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Priority claimed from AU2017903421A external-priority patent/AU2017903421A0/en
Application filed by University Of South Australia filed Critical University Of South Australia
Publication of WO2019036770A1 publication Critical patent/WO2019036770A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/25—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
    • A61L2202/20—Targets to be treated
    • A61L2202/24—Medical instruments, e.g. endoscopes, catheters, sharps
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates generally to antimicrobial compositions and methods for their use.
  • the compositions comprise a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent.
  • Antimicrobial agents encompassed by the present invention include antibiotics, antiseptics, and antifungals.
  • An antimicrobial is an agent that kills, or inhibits the growth of, microorganisms.
  • Antimicrobials can be classified based on the microorganism they primarily act against. For example, antibiotics target bacteria, whereas antifungals are used against fungi.
  • antiseptics are typically used to reduce or prevent the possibility of infection, sepsis, or putrefaction caused by microorganisms.
  • the present invention is predicated, in part, on the surprising finding that the action of existing antimicrobials, such as antibiotics and antiseptics, is potentiated when the antimicrobials are combined with a glycerolipid.
  • This enables the formulation and preparation of therapeutically effective antimicrobial compositions, which, in the absence of the glycerolipid would otherwise be ineffective due to microorganism resistance to the antimicrobial alone, or would require a significantly higher concentration of the antimicrobial to achieve the same effect.
  • the present invention provides a composition suitable for administration to a subject, the composition comprising:
  • the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid. In some embodiments, the monoglyceride content of the glycerolipid is about 45% to about 75% w/w of the total glyceride content of the glycerolipid. In some embodiments, the monoglyceride content of the glycerolipid is about 50% to about 60% w/w of the total glyceride content of the glycerolipid.
  • the diglyceride content of the glycerolipid is about 20% to about 50% w/w of the total glyceride content of the glycerolipid. In some embodiments, the diglyceride content of the glycerolipid is about 30% to about 40% w/w of the total glyceride content of the glycerolipid.
  • the glycerolipid comprises only medium chain length fatty acids.
  • the medium chain length fatty acids comprise caprylic acid.
  • the caprylic acid comprises >50% w/w of the total fatty acid content of the glycerolipid. In some embodiments, the caprylic acid comprises about 55% to about 99% w/w of the total fatty acid content of the glycerolipid.
  • the medium chain length fatty acids comprise capric acid.
  • the capric acid comprises ⁇ 50% w/w of the total fatty acid content of the glycerolipid. In some embodiments, the capric acid comprises about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid.
  • the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.
  • the antimicrobial agent is selected from an antibiotic, an antiseptic, and an antifungal.
  • the antibiotic is selected from the group consisting of a protein synthesis inhibitor, a cell wall synthesis inhibitor, a beta-lactam antibiotic, a beta- lactamase inhibitor, a lipopeptide, a peptidoglycan synthesis inhibitor, a DNA synthesis inhibitor, a RNA synthesis inhibitor, a mycolic acid synthesis inhibitor, a mechanosensitive channel of large conductance (MscL), and a folic acid synthesis inhibitor, or a combination of the aforementioned antibiotics.
  • the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.
  • the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.
  • the antiseptic is chlorhexidine.
  • the antifungal is selected from an azole and/or amphotericin B.
  • the composition is in the form of a liquid, gel, paste, cream, powder, or aerosol. [0025] In some embodiments, the composition is formulated for topical administration to the subject.
  • the glycerolipid potentiates the activity of the antimicrobial for the treatment or prevention of an infection in the subject.
  • the subject has become resistant to the antimicrobial when administered in the absence of the glycerolipid.
  • the infection is a bacterial infection.
  • the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis.
  • the bacterial infection is due to MRSA.
  • the bacterial infection forms part of a biofilm. In some embodiments, the bacterial infection comprises an infected wound.
  • the infection is a fungal infection.
  • the fungal infection is due to Candida albicans.
  • the subject is a human or an animal.
  • the present invention provides a method for the treatment or prevention of an infection in a subject, the method comprising administering to the subject an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid. In some embodiments, the monoglyceride content of the glycerolipid is 45% to 75% w/w of the total glyceride content of the glycerolipid. In some embodiments, the monoglyceride content of the glycerolipid is about 50% to about [0033] In some embodiments of the second aspect of the present invention, the diglyceride content of the glycerolipid is 20% to 50% w/w of the total glyceride content of the glycerolipid. In some embodiments, the diglyceride content of the glycerolipid is about 32% to about 40% w/w of the total glyceride content of the glycerolipid.
  • the glycerolipid comprises only medium chain length fatty acids.
  • the medium chain length fatty acids comprise caprylic acid.
  • the caprylic acid comprises >50% w/w of the total fatty acid content of the glycerolipid. In some embodiments, the caprylic acid comprises about 55% to about 99% w/w of the total fatty acid content of the glycerolipid.
  • the medium chain length fatty acids comprise capric acid.
  • the capric acid comprises ⁇ 50% w/w of the total fatty acid content of the glycerolipid. In some embodiments, the capric acid comprises about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid.
  • the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.
  • the antimicrobial agent is selected from an antibiotic, an antiseptic, and an antifungal.
  • the antibiotic is selected from the group consisting of a protein synthesis inhibitor, a cell wall synthesis inhibitor, a beta-lactam antibiotic, a beta-lactamase inhibitor, a lipopeptide, a peptidoglycan synthesis inhibitor, a DNA synthesis inhibitor, a RNA synthesis inhibitor, a mycolic acid synthesis inhibitor, a mechanosensitive channel of large conductance (MscL), and a folic acid synthesis inhibitor, or a combination of the aforementioned antibiotics.
  • the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.
  • the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.
  • the antiseptic is chlorhexidine.
  • the antifungal is selected from an azole and/or amphotericin B.
  • the composition is in the form of a liquid, gel, paste, cream, powder, or aerosol.
  • the composition is topically administered to the subject.
  • the infection has become resistant to the antimicrobial when administered in the absence of the glycerolipid.
  • the infection is a bacterial infection.
  • the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis.
  • the bacterial infection is due to MRSA.
  • the bacterial infection forms part of a biofilm.
  • the bacterial infection comprises an infected wound.
  • the infection is a fungal infection.
  • the fungal infection is due to Candida albicans.
  • the subject is a human or an animal.
  • the present invention provides use of a composition in the manufacture of a medicament for the treatment or prevention of an infection in a subject, wherein the composition comprises a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a kit for use in, or when used for, the treatment or prevention of an infection in a subject, the kit comprising:
  • the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method of reducing the viability of a microorganism, the method comprising exposing the microorganism to an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for potentiating the activity of an antimicrobial agent in a subject, the method comprising administering to the subject an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antibiotic, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides use of a composition in the manufacture of a medicament for potentiating the effect of an antimicrobial agent in a subject, wherein the composition comprises a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antibiotic, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for reducing the dose of an antimicrobial agent required to treat or prevent an infection in a subject, the method comprising administering to the subject an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent thereby reducing the dose of the antimicrobial agent required to treat or prevent the infection in the subject, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides use of a composition in the manufacture of a medicament for reducing the dose of an antimicrobial agent required to treat or prevent an infection in a subject, wherein the composition comprises a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antibiotic thereby reducing the dose of the antimicrobial agent required to treat or prevent the infection in the subject, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for increasing the potency of an antimicrobial agent required to treat or prevent an infection in a subject, the method comprising administering to the subject an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid increases the potency of the antimicrobial agent required to treat or prevent the infection in the subject, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides use of a composition in the manufacture of a medicament for increasing the potency of an antimicrobial agent required to treat or prevent an infection in a subject, wherein the composition comprises a glycerolipid and an antimicrobial agent, wherein the glycerolipid increases the potency of the antimicrobial agent required to treat or prevent the infection in the subject, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for reducing viability of a microorganism resistant to an antimicrobial agent, the method comprising exposing the microorganism to an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method of treating an instrument, a medical device, an implant, or a surface, the method comprising exposing the instrument, medical device, implant, or surface, to a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for the treatment or prevention of a Staphylococcus aureus infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, vancomycin, and chloramphenicol.
  • the present invention provides a method for the treatment or prevention of a MRSA infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefepime, gentamicin, erythromycin, tobramycin, and ciprofloxacin.
  • the present invention provides a method for the treatment or prevention of a Pseudomonas aeruginosa infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, cefepime, and tobramycin.
  • the present invention provides a method for the treatment or prevention of an Escherichia coli infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and tobramycin.
  • the present invention provides a method for the treatment or prevention of a Klebsiella pneumoniae infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and colistin.
  • the present invention provides a method for the treatment or prevention of an Acinetobacter baumannii infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of colistin, chloramphenicol, gentamicin, amikacin, and ciprofloxacin.
  • the present invention provides a method for the treatment or prevention of an Enterococcus faecium infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, meropenem, erythromycin, and bacitracin.
  • the present invention provides a method for the treatment or prevention of a Staphylococcus epidermidis infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antiseptic, wherein the glycerolipid is Capmul MCM and the antiseptic is chlorhexidine.
  • the present invention provides a method for the treatment or prevention of an Enterococcus faecalis infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is tobramycin.
  • FIGURE 1 - is a schematic of the microdilution method used for determination of the minimum inhibitory concentration (MIC) of various bacterial strains.
  • FIGURE 2 graphs showing the results of a checkerboard assay in the Staphylococcus aureus clinical isolate SA CM .
  • A Minimum inhibitory concentration
  • B minimum biofilm inhibitory concentration
  • FIGURE 3 graphs showing the results of a checkerboard assay in the Staphylococcus aureus clinical isolate SA CM .
  • Minimum inhibitory concentration (MIC) as a function of the concentration of glycerolipid Imwitor 742 (A) or glycerolipid Imwitor 988 (B), in the presence of the antibiotic gentamicin.
  • Data represents mean ⁇ SD of at least 2- 3 independent experiments.
  • FIGURE 4 graphs showing the results of a checkerboard assay in the methicillin resistant Staphylococcus aureus (MRSA) clinical isolate MRSA CM .
  • MRSA methicillin resistant Staphylococcus aureus
  • A Minimum inhibitory concentration
  • B minimum biofilm inhibitory concentration
  • Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 5 graphs showing the results of a checkerboard assay in the methicillin resistant Staphylococcus aureus (MRSA) ATCC 33591 strain.
  • MRSA methicillin resistant Staphylococcus aureus
  • A Minimum inhibitory concentration
  • B minimum biofilm inhibitory concentration
  • Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 6 graphs showing the results of a checkerboard assay in the Pseudomonas aeruginosa clinical isolate PA CM .
  • A Minimum inhibitory concentration (MIC); and
  • B minimum biofilm inhibitory concentration (MBIC) are shown as a function of glycerolipid concentration in the presence of the antibiotic cefepime. Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 7 graphs showing the results of a checkerboard assay in the Pseudomonas aeruginosa clinical isolate PA CM .
  • A Minimum inhibitory concentration (MIC); and
  • B minimum biofilm inhibitory concentration (MBIC) are shown as a function of glycerolipid concentration in the presence of the antibiotic gentamicin. Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 8 graphs showing the results of a checkerboard assay in the Escherichia coli ATCC 1 1229 strain.
  • (A) Minimum inhibitory concentration (MIC); and (B) minimum biofilm inhibitory concentration (MBIC) are shown as a function of glycerolipid concentration in the presence of the antibiotic cefazolin. Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 9 - graphs showing the results of a checkerboard assay in the Escherichia coli ATCC 1 1229 strain.
  • A Minimum inhibitory concentration
  • MBIC minimum biofilm inhibitory concentration
  • FIGURE 10 graphs showing the results of a checkerboard assay in the Klebsiella pneumoniae ATCC 700603 strain.
  • A Minimum inhibitory concentration (MIC); and
  • B minimum biofilm inhibitory concentration (MBIC) are shown as a function of glycerolipid concentration in the presence of the antibiotic cefazolin. Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 11 graphs showing the results of a checkerboard assay in the Klebsiella pneumoniae ATCC 700603 strain.
  • A Minimum inhibitory concentration (MIC); and
  • B minimum biofilm inhibitory concentration (MBIC) are shown as a function of glycerolipid concentration in the presence of the antibiotic gentamicin. Data represents mean ⁇ SD of at least 2-3 independent experiments.
  • FIGURE 12 graphs showing the susceptibility of Staphylococcus aureus ATCC 33591 strain towards antibiotic treatment alone or in combination with glycerolipid.
  • Left panels (A, C and E) represent the MIC values obtained in planktonic bacteria, the right panels (B, D and F) show corresponding biofilm MBICs.
  • Left panels (A and C) represent the MIC values obtained in planktonic bacteria, and the right panels (B and D) show corresponding biofilm MBICs.
  • FIGURE 14 graphs showing susceptibility of the Enterobacter species Escherichia coli clinical isolate CI 8 towards antibiotic treatment alone (Tobramycin - top panels A and B; and Gentamicin - bottom panels C and D) or in combination with glycerolipid.
  • Left panels (A and C) represent the MIC values obtained in planktonic bacteria
  • the right panels (B and D) show corresponding biofilm MBICs.
  • FIGURE 15 shows susceptibility of Klebsiella pneumoniae ATCC 700603 strain towards antibiotic treatment alone or in combination with glycerolipid.
  • Left panels (A, C and E) represent the MIC values obtained in planktonic bacteria
  • the right panels (B, D and F) show corresponding biofilm MBICs.
  • Left panels (A and C) represent the MIC values obtained in planktonic bacteria, and the right panels (B and D) show corresponding biofilm MBICs.
  • Left panels (A and C) represent the MIC values obtained in planktonic bacteria, and the right panels (B and D) show corresponding biofilm MBICs.
  • FIGURE 18 graphs showing susceptibility of Staphylococcus epidermidis ATCC strains to Chlorhexidine (a topical antiseptic) treatment alone or in combination with glycerolipid.
  • A S. epidermidis ATCC 35984 planktonic susceptibility
  • B S. epidermidis ATCC 14990 planktonic susceptibility performed in duplicate. No susceptibility cut-off published/known by EUCAST. Data points represented as the mean +/- SD.
  • FIGURE 19 - a graph showing biofilm susceptibility of Escherichia coli ATCC 1 1229 strain to Gentamicin treatment alone or in combination with glycerolipid. Data points represented as the mean +/- SD.
  • FIGURE 20 - a graph showing susceptibility of Enterococcus faecalis ATCC 29212 strain to Tobramycin treatment alone or in combination with glycerolipid. Data points represented as the mean +/- SD. LLIR - low level intrinsic resistance.
  • FIGURE 21 graphs showing susceptibility of Klebsiella pneumoniae ATCC 700603 strain to Gentamicin and Colistin treatment alone or in combination with glycerolipid. Gentamicin susceptibility was investigated in both (A) planktonic and (B) biofilm susceptibility assays. Colistin susceptibility was investigated in both (C) planktonic and (D) biofilm susceptibility assays. Data points represented as the mean +/- SD.
  • FIGURE 22 graphs showing susceptibility of Enterococcus faecium ATCC 19434 strain to topical antibiotic treatment alone or in combination with glycerolipid.
  • Tobramycin susceptibility was investigated in both planktonic (A and D) and biofilm (B, C, and E) susceptibility assays. Data points represented as the mean +/- SD. HLAR - high level aminoglycoside resistance, LLIR - low level intrinsic resistance.
  • FIGURE 23 graphs showing susceptibility of Acinetobacter baumannii ATCC 19606 strain to Gentamicin and Colistin treatment alone or in combination with glycerolipid.
  • A Gentamicin susceptibility was investigated in planktonic susceptibility assays, whereas Colistin was tested in both
  • B planktonic and
  • C biofilm susceptibility assays. Data points represented as the mean +/- SD from the mean.
  • FIGURE 24 graphs showing susceptibility of Staphylococcus aureus (MRSA) ATCC 33591 strain towards to antibiotic treatment alone or in combination with glycerolipid.
  • MRSA Staphylococcus aureus
  • A Gentamicin
  • B Erythromycin
  • C Tobramycin susceptibility was investigated in planktonic susceptibility assays. Data points represented as the mean +/- SD.
  • FIGURE 25 graphs showing susceptibility of Enterococcus clinical isolates to topical antibiotic treatment alone or in combination with glycerolipid.
  • Enterococcus faecium clinical isolate CI 1 Gentamicin susceptibility and
  • Enterococcus faecalis clinical isolate CI 2 Tobramycin susceptibility was investigated in planktonic susceptibility assays. Data points represented as the mean +/- SD. HLAR - high level aminoglycoside resistance, LLIR - low level intrinsic resistance.
  • FIGURE 26 graphs showing susceptibility of Staphylococcus aureus (MRSA) clinical isolates to topical antibiotic treatment alone or in combination with glycerolipid.
  • MRSA clinical isolate CI Ba Gentamicin susceptibility was investigated in planktonic susceptibility assays.
  • MRSA clinical isolate CI Ru Ciprofloxacin susceptibility was investigated in both (B) planktonic and (C) biofilm susceptibility assays.
  • MRSA clinical isolate CI Se Gentamicin susceptibility was investigated in (D) planktonic and (E) biofilm susceptibility assays. Data points represented as the mean +/- SD.
  • FIGURE 27 graphs showing susceptibility of Acinetobacter baumannii clinical isolate CI 17 to topical antibiotic treatment alone or in combination with glycerolipid.
  • Susceptibility of Acinetobacter baumannii clinical isolate CI 17 against (A) Gentamicin and (B) Colistin were investigated in planktonic susceptibility assays.
  • Susceptibility of Acinetobacter baumannii clinical isolate CI 17 against (C) Amikacin, (D) Ciprofloxacin, (E) Colistin and (F) Tobramycin were investigated in biofilm susceptibility assays. Data points represented as the mean +/- SD.
  • FIGURE 28 graphs showing susceptibility of Acinetobacter baumannii clinical isolate CI 19 to Colistin treatment alone or in combination with glycerolipid. Susceptibility of Acinetobacter baumannii clinical isolate CI 19 against Colistin was investigated in both (A) planktonic and (B) biofilm susceptibility assays. Data points represented as the mean +/- SD.
  • Susceptibility of Pseudomonas aeruginosa clinical isolate CI 18 against Tobramycin was investigated in (A) planktonic and (B) biofilm susceptibility assays.
  • Susceptibility of Pseudomonas aeruginosa clinical isolate CI Ma against Gentamicin was investigated in (C) planktonic and (D) biofilm susceptibility assays. Data points represented as the mean +/- SD.
  • FIGURE 30 - a graph showing the results of an artificial dermis infected with Staphylococcus aureus (MRSA) ATCC 33591 strain.
  • Y-axis represents the total colony forming units (CFUs) for each treatment (X-axis).
  • CFUs colony forming units
  • the present invention provides compositions and methods for treating or preventing infections, reducing the viability of a microorganism, reducing the dose of an antimicrobial agent required to treat or to prevent an infection, and increasing the potency of an antimicrobial agent required to treat or prevent an infection.
  • compositions, methods, products, and uses thereof that have one or more advantages.
  • some of the advantages of some embodiments disclosed herein include one or more of the following: new products and compositions for the treatment of infections, including bacterial infections associated with a biofilm; identification of a new treatment regime for infections, such as bacterial and fungal infections; identification of a treatment regime that is suitable for the treatment of bacteria in a biofilm; identification that the activity of an antimicrobial agent can be enhanced by co-application with a glycerolipid; a treatment regime that can utilise lower concentrations of antimicrobial agents that target infections or can improve the efficacy of such agents than when used alone; a new regime for the treatment of bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and
  • the present invention provides a composition suitable for administration to a subject, the composition comprising:
  • the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • a "glycerolipid” refers to a lipid that is composed of mono-, di- and/or tri-substituted glycerols. Accordingly, a glycerolipid encompassed by the present invention is uncharged (neutral). As would be understood by a person skilled in the art, the glycerolipid can be formed through the esterification of fatty acids with glycerol. For example, in some embodiments the glycerolipid is formed by linking glycerol to a C6 to C22 fatty acid acyl group. The acyl group may be branched or unbranched, saturated or unsaturated.
  • the acyl group is unbranched and saturated.
  • the acyl group may be derived from a saturated fatty acid, e.g., caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, or behenic acid.
  • a glycerolipid for use in the present invention would be known in the art.
  • a glycerolipid can be prepared through the glycerolysis of select fats and oils, or can be prepared by esterification of glycerin with specific fatty acids.
  • a glycerolipid may be obtained from coconut oil, or palm oil, or palm kernel oil by fractionated distillation followed by esterification with glycerol.
  • the glycerolipid may comprise any combination of mono-substituted, di-substituted and/or tri-substituted glycerols provided that the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid. Methods for measuring the glyceride content of the glycerolipid would be known in the art.
  • the mono-, di-, and tri-glyceride and free glycerol content of a glycerolipid can be quantified by high performance liquid chromatography (HPLC), gas chromatography (GC), or liquid chromatography/mass spectrometry (LC/MS) using analytical standards such as the "Mono-, Di-, and Triglycerides Kit” (Sigma Aldrich, Castle Hill, NSW).
  • HPLC high performance liquid chromatography
  • GC gas chromatography
  • LC/MS liquid chromatography/mass spectrometry
  • the total triglyceride content of the glycerolipid is ⁇ 10% w/w, ⁇ 9% w/w, ⁇ 8% w/w, ⁇ 7% w/w, ⁇ 6% w/w, ⁇ 5% w/w, ⁇ 4% w/w, ⁇ 3% w/w, ⁇ 2% w/w, or ⁇ 1% w/w, of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid.
  • the monoglyceride content may be about 45% to 95% w/w, about 45% to 90% w/w, about 45% to 85% w/w, about 45% to 80% w/w, about 45% to 70% w/w, about 45% to 65% w/w, about 45% to 60% w/w, about 45% to 55% w/w, about 45% to 50% w/w, about 50% to 100% w/w, about 50% to 95% w/w, about 50% to 90% w/w, about 50% to 85% w/w, about 50% to 80% w/w, about 50% to 75% w/w, about 50% to 70% w/w, about 50% to 65% w/w, about 50% to 60% w/w, about 50% to 55% w/w
  • the monoglyceride content of the glycerolipid is about 50% w/w, about 51 % w/w, about 52% w/w, about 53% w/w, about 54% w/w, about 55% w/w, about 56% w/w, about 57% w/w, about 58% w/w, about 59% w/w, or about 60% w/w, of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 100% w/w of the total glyceride content of the glycerolipid. That is, in some embodiments, the glycerolipid only comprises monoglycerides.
  • the diglyceride content of the glycerolipid is about 20% to about 50% w/w of the total glyceride content of the glycerolipid.
  • the diglyceride content may be about 20% to 45% w/w, about 20% to 40% w/w, about 20% to 35% w/w, about 20% to 30% w/w, about 20% to 25% w/w, about 25% to 50% w/w, about 25% to 45% w/w, about 25% to 40% w/w, about 25% to 35% w/w, about 25% to 30% w/w, about 30% to 50% w/w, about 30% to 45% w/w, about 30% to 40% w/w, about 30% to 35% w/w, about 35% to 50% w/w, about 35% to 45% w/w, about 35% to 40% w/w, about 40% to 50% w/w, about 40% to 45% w/w, or about 45% to 50% w/w/w.
  • the diglyceride content of the glycerolipid is about 30% w/w, about 31 % w/w, about 32% w/w, about 33% w/w, about 34% w/w, about 35% w/w, about 36% w/w, about 37% w/w, about 38% w/w, about 39% w/w, or about 40% w/w, of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 60% w/w
  • the diglyceride content of the glycerolipid is about 33% w/w
  • the triglyceride content of the glycerolipid is about 5% w/w, of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 59% w/w
  • the diglyceride content of the glycerolipid is about 34% w/w
  • the triglyceride content of the glycerolipid is about 6% w/w, of the total glyceride content of the glycerolipid.
  • the monoglyceride content of the glycerolipid is about 50% w/w
  • the diglyceride content of the glycerolipid is about 39% w/w
  • the triglyceride content of the glycerolipid is about 8% w/w, of the total glyceride content of the glycerolipid.
  • the glycerolipid may be formed by linking glycerol to a C6 to C22 fatty acid acyl group.
  • the glycerolipid may only comprise medium chain length fatty acids, i.e. fatty acids with aliphatic tails of 6 to 12 carbons.
  • the acyl group may be derived from, for example, caprylic acid (C8), capric acid (C10), and/or lauric acid (C12).
  • the glycerolipid only comprises caprylic acid and capric acid.
  • the glycerolipid comprises the medium chain length fatty acid carpylic acid, wherein the caprylic acid comprises >50% w/w of the total fatty acid content of the glycerolipid.
  • the caprylic acid content of the glycerolipid is about 55% to about 99% w/w of the total fatty acid content of the glycerolipid.
  • the caprylic acid content may be about 55% to 95% w/w, about 55% to 90% w/w, about 55% to 85% w/w, about 55% to 80% w/w, about 55% to 75% w/w, about 55% to 70% w/w, about 55% to 65% w/w, about 55% to 60% w/w, about 60% to 99% w/w, about 60% to 95% w/w, about 60% to 90% w/w, about 60% to 85% w/w, about 60% to 80% w/w, about 60% to 75% w/w, about 60% to 70% w/w, about 60% to 65% w/w, about 65% to 99% w/w, about 65% to 95% w/w, about 65% to 90% w/w, about 65% to 85% w/w, about 65% to 80% w/w, about 65% to 75% w/w, about 65% to 70% w/w, about 70% to 99% w/
  • the glycerolipid comprises the medium chain length fatty acid capric acid, wherein the capric acid comprises ⁇ 50% w/w of the total fatty acid content of the glycerolipid.
  • the capric acid content of the glycerolipid is about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid.
  • the capric acid content may be about 1 % to 40% w/w, about 1 % to 35% w/w, about 1 % to 30% w/w, about 1 % to 25% w/w, about 1 % to 20% w/w, about 1 % to 15% w/w, about 1 % to 10% w/w, about 1 % to 5% w/w, about 5% to 42% w/w, about 5% to 40% w/w, about 5% to 35% w/w, about 5% to 30% w/w, about 5% to 25% w/w, about 5% to 20% w/w, about 5% to 15% w/w, about 5% to 10% w/w, about 10% to 42% w/w, about 10% to 40% w/w, about 10% to 35% w/w, about 10% to 30% w/w, about 10% to 25% w/w, about 10% to 20% w/w, about 10% to 15% w/w, about 5% to 10% w/w,
  • the caprylic acid content of the glycerolipid is about 83% w/w, and the capric acid content of the glycerolipid is about 17% w/w, of the total fatty acid content of the glycerolipid.
  • the caprylic acid content of the glycerolipid is about 58% w/w, and the capric acid content of the glycerolipid is about 42% w/w, of the total fatty acid content of the glycerolipid.
  • the caprylic acid content of the glycerolipid is about 99% w/w, and the capric acid content of the glycerolipid is about 1 % w/w, of the total fatty acid content of the glycerolipid.
  • the glycerolipid may be purchased from commercial sources such as ABITEC Corporation (Columbus, Ohio, USA) or Cremer Oleo GmbH & Co. KG (Hamburg, Germany).
  • the glycerolipid may be selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.
  • the antimicrobial agent is an antibiotic. Accordingly, in a further aspect, the present invention provides a composition suitable for administration to a subject, the composition comprising:
  • the glycerolipid potentiates the activity of the antibiotic, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • Antibiotics for use in the composition of the present invention may be selected from the group consisting of a protein synthesis inhibitor, a cell wall synthesis inhibitor including beta-lactam antibiotics, beta-lactamase inhibitors and peptidoglycan synthesis inhibitors, a lipopeptide including daptomycin, a DNA synthesis inhibitor, a RNA synthesis inhibitor, a mycolic acid synthesis inhibitor including isoniazid, a mechanosensitive channel of large conductance (MscL), and a folic acid synthesis inhibitor, or a combination of the aforementioned antibiotics.
  • a protein synthesis inhibitor a cell wall synthesis inhibitor including beta-lactam antibiotics, beta-lactamase inhibitors and peptidoglycan synthesis inhibitors
  • a lipopeptide including daptomycin
  • DNA synthesis inhibitor a DNA synthesis inhibitor
  • RNA synthesis inhibitor a RNA synthesis inhibitor
  • mycolic acid synthesis inhibitor including isoniazid
  • MscL mechanosensitive channel of
  • Antibiotics for use in the present invention can be purchased from relevant commercial suppliers such as Sigma-Aldrich (Castle Hill, NSW, Australia), and methods for their use are known in the art, for example as described in “Therapeutic Guidelines - Antibiotic", Version 15, 2014, published by eTG complete.
  • protein synthesis inhibitors include those which stop or slow the growth or proliferation of cells by inhibiting the processes that lead to protein production. Such protein synthesis inhibitors typically (but not always) act by disrupting the activity of the ribosome during translation of mRNA.
  • antibiotics which are classed as protein synthesis inhibitors include, but are not limited to, tetracyclines (such as demeclocycline, doxycycline, minocycline, oxytetracycline and tetracycline, or derivatives thereof such as tigecycline), aminoglycosides (such as amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin and spectinomycin), phenicols (such as chloramphenicol or derivatives thereof such as thiamphenicol), macrolides (such as azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin and spiramycin), lincosamides (such as clindamycin and lincomycin), fusidic acid, puromycin, streptogramins (such as pristinamycin, di
  • cell wall synthesis inhibitors include, but are not limited to, carbapenems (such as ertapenem, doripenem, imipenem and meropenem), penicillins (such as amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, fluloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin and ticarcillin), cephalosporins (such as cefadroxil, cefazolin, cefalotin, cephalexin, cefaclor, cefamandole, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten,
  • DNA synthesis inhibitors include, but are not limited to, quinolones or fluoroquinolones (such as ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin,grepafloxacin, sparfloxacin and temafloxacin), and metronizadole.
  • quinolones or fluoroquinolones such as ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin,grepafloxacin, sparfloxacin and temafloxacin
  • fluoroquinolones such as
  • RNA synthesis inhibitors include, but are not limited to, rifamycins such as rifampin and rifapentine.
  • folic acid synthesis inhibitors include, but are not limited to, sulfonamides (such as mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfanilamide, sulfasalazine, sulfisoxazole, trimethoprim-sulfamethoxazole and sulfonamidochrysoidine) and pyrimethamine.
  • sulfonamides such as mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfanilamide, sulfasalazine, sulfisoxazole
  • the antibiotics for use in the composition of the present invention may also be selected from the group consisting of geldanamycin, herbimycin, rifaximin, furazolidone, nitrofurantoin, clofazimine, dapsone, capreomycin, cycloserine, ethambutol, pyrazinamide, rifabutin, arsphenamine, platensimycin and tinidazole.
  • the antibiotics for use in the composition of the present invention are selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.
  • the antibiotic may be selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.
  • the antimicrobial agent is an antiseptic. Accordingly, in a further aspect, the present invention provides a composition comprising:
  • the glycerolipid potentiates the activity of the antiseptic, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • Antiseptics for use in the present invention include alcohols, chlorhexidine, triclosan, hydrogen peroxide, iodine, octenidine dihydrochloride, polyhexanide, Balsam of Peru, and Dakin's solution.
  • chlorhexidine is used.
  • the composition is suitable for administration to a subject.
  • glycerolipid potentiates the activity of the antibiotic or antiseptic.
  • potentiate the activity should be taken to mean to enhance or increase the activity of the antibiotic or antiseptic to a level which is greater than the activity of the antibiotic or antiseptic when used in the absence of the glycerolipid.
  • the glycerolipid and antibiotic or antiseptic are acting synergistically.
  • the activity of the antibiotic or antiseptic may be enhanced or increased by at least 1 %, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or greater, or by 1 -fold, 2-fold, 3-fold, 4-fold, 5-fold, 6.0-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40-fold, 45-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 125-fold, 150-fold, 175-fold, 200-fold, 225-fold, 250-fold, 275-fold, 300- fold, 400-fold, 500-fold, or greater, when compared to the activity of the antibiotic or antiseptic when used in the absence of the glycerolipid.
  • the activity may be reflective of the measured minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and/or minimum biofilm inhibitory concentration (MBIC) of the antibiotic or antiseptic, or of the short-kill assay times with respect to an in vitro analysis.
  • the combination of the glycerolipid and antibiotic or antiseptic may decrease the MIC, MBC, and/or MBIC of the antibiotic or antiseptic, or reduce the short-kill time for bacteria which are resistant to the antibiotic or antiseptic when administered in the absence of the glycerolipid.
  • the activity may also be observed in the form of an improvement of the condition of the subject, for example, as determined by a clinician.
  • Methods for determination of MICs, MBCs and MBICs would be well known in the art, some of which are described herein.
  • MIC values for various antibiotics and bacteria can be obtained from the Antimicrobial Index at http://antibiotics.toku-e.com.
  • the MIC or MBIC for the antibiotic or antiseptic is reduced from 1024 mg/l to 0.0625 mg/l when administered with the glycerolipid.
  • the MIC or MBIC for the antibiotic may be reduced from 1024 mg/l to 128 mg/l, 256 mg/l to 64 mg/l, 128 mg/l to 4 mg/l, 128 mg/l to 2 mg/l, 64 mg/l to 4 mg/l, 32 mg/l to 2 mg/l, 32 mg/l to 1 mg/l, 32 mg/l to 0.125 mg/l, 16 mg/l to 4 mg/l, 16 mg/l to 2 mg/l, 8 mg/l to 4 mg/l, 8 mg/l to 0.5 mg/l, 4 mg/l to 0.0625 mg/l, or 0.5 mg/l to 0.03 mg/l, when administered with the glycerolipid.
  • Other ranges are contemplated.
  • the composition of the present invention is suitable for administration to a subject.
  • the composition can take a number of physical forms depending on the nature of the use of the composition and required mode of administration.
  • one route of administration may include topical administration and therefore the composition may be in the form of a liquid, gel, paste, lotion, cream, powder, and the like, including solutions such as mouthwashes, for topical oral administration.
  • Another route of administration may be systemic administration and therefore the composition may be in the form of an injectable solution, may be in a form suitable for oral administration such as a tablet, pill, capsule, or may be in another dosage form useful for systemic administration of agents.
  • the composition may also be in the form of an aerosol, nebulizer or dry powder for inhalation delivery.
  • Other forms of administration may include delivery by way of a scaffold, such as a biomaterial scaffold including a scaffold produced from collagen, hydroxyapatite, ⁇ -tricalcium phosphate or a combination thereof. Other routes of administration are contemplated.
  • the composition may be administered alone or may be delivered in the form of a suitable pharmaceutical composition, for example in a mixture with other therapeutic substances and/or other substances that enhance, stabilise or maintain the activity of the components of the composition.
  • an administration vehicle e.g., liquid, gel, paste, powder, cream, pill, tablet, capsule, injectable solution, aerosol, etc
  • the pharmaceutical composition may also include the use of one or more pharmaceutically acceptable carriers or additives, including pharmaceutically acceptable salts, amino acids, polypeptides, polymers, solvents, buffers, excipients and bulking agents, taking into consideration the particular physical and chemical characteristics of the composition to be administered.
  • the carrier may be chosen based on various considerations including the route of administration, the antimicrobial agent being delivered and the time course of delivery of the composition.
  • pharmaceutically acceptable carrier refers to a substantially inert solid, semi-solid or liquid filler, diluent, excipient, encapsulating material or formulation auxiliary of any type.
  • An example of a pharmaceutically acceptable carrier is physiological saline.
  • Other physiologically acceptable carriers and their formulations are known in the art.
  • materials which can serve as pharmaceutically acceptable carriers include sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; detergents such as TWEEN 80; buffering agents such as magnesium hydroxide and aluminium hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; and phosphate buffer solutions, as well as other non-toxic compatible lubricants such
  • the composition may be formulated for topical administration, e.g. transdermal administration.
  • Transdermal administrations are understood to include all administrations across the surface of the body and the inner linings of bodily passages including epithelial and mucosal tissues.
  • Such administrations may be carried out using the composition of the present invention as described herein, in the form of a liquid, gel, paste, lotion, cream, ointment, powder, foam, patch, suspension, solution, and a suppository (rectal and vaginal), or other suitable form.
  • a cream is a formulation that contains water and oil and is stabilized with an emulsifier.
  • Lipophilic creams are called water-in-oil emulsions, and hydrophilic creams oil- in-water emulsions.
  • the cream base for water-in-oil emulsions are normally absorption bases such as vaseline, ceresin or lanolin.
  • the bases for oil-in-water emulsions are mono- , di-, and tri-glycerides of fatty acids or fatty alcohols with soaps, alkyl sulphates or alkyl polyglycol ethers as emulsifiers.
  • a lotion is an opaque, thin, non-greasy emulsion liquid dosage form for external application to the skin, which generally contains a water-based vehicle with greater than 50% of volatiles and sufficiently low viscosity that it may be delivered by pouring. Lotions are usually hydrophilic, and contain greater than 50% of volatiles as measured by LOD (loss on drying). A lotion tends to evaporate rapidly with a cooling sensation when rubbed onto the skin.
  • a paste is an opaque or translucent, viscous, greasy emulsion or suspension semisolid dosage form for external application to the skin, which generally contains greater than 50% of hydrocarbon-based or a polyethylene glycol-based vehicle and less than 20% of volatiles.
  • a paste contains a large proportion (20-50%) of dispersed solids in a fatty or aqueous vehicle.
  • An ointment is an opaque or translucent, viscous, greasy emulsion or suspension semisolid dosage form for external application to the skin, which generally contains greater than 50% of hydrocarbon-based or a polyethylene glycol-based vehicle and less than 20% of volatiles.
  • An ointment is usually lipophilic, and contains >50% of hydrocarbons or polyethylene glycols as the vehicle and ⁇ 20% of volatiles as measured by LOD. An ointment tends not to evaporate or be absorbed when rubbed onto the skin.
  • a gel is usually a translucent, non-greasy emulsion or suspension semisolid dosage form for external application to the skin, which contains a gelling agent in quantities sufficient to impart a three-dimensional, cross-linked matrix.
  • a gel is usually hydrophilic, and contains sufficient quantities of a gelling agent such as starch, cellulose derivatives, carbomers, magnesium-aluminum silicates, xanthan gum, colloidal silica, aluminium or zinc soaps.
  • composition of the present invention when in a form for topical administration, may further include drying agents, anti-foaming agents, buffers, neutralizing agents, agents to adjust pH, colouring agents and decolouring agents, emollients, emulsifying agents, emulsion stabilizers and viscosity builders, humectants, odorants, preservatives, antioxidants, and chemical stabilizers, solvents, and thickening, stiffening, and suspending agents, and a balance of water or solvent.
  • Transdermal administration may also be accomplished through the use of a transdermal patch containing the active components of the composition and a carrier that is inert to the active components, is non-toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin.
  • the carrier may take any number of forms such as creams and ointments, pastes, gels, and occlusive devices.
  • the creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in- water or water-in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable.
  • occlusive devices may be used to release the active ingredient into the blood stream such as a semi-permeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient.
  • Transdermal formulations are known in art and may be formulated by a skilled person.
  • composition of the present invention may be formulated for administration by way of a suppository.
  • Suppository formulations may be made from traditional materials, including cocoa butter, with or without the addition of waxes to alter the suppository's melting point, and glycerin.
  • Water soluble suppository bases such as polyethylene glycols of various molecular weights, may also be used.
  • composition of the present invention may be formulated for parenteral administration.
  • parenteral as used herein includes subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal, and intracranial injection or infusion techniques.
  • the composition When administered parenterally, the composition will normally be in a unit dosage, sterile injectable, form (solution, suspension or emulsion) which is preferably isotonic with the blood of the recipient with a pharmaceutically acceptable carrier.
  • sterile injectable forms are sterile injectable aqueous or oleaginous suspensions. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents.
  • the sterile injectable forms may also be sterile injectable solutions or suspensions in non-toxic parenterally-acceptable diluents or solvents, for example, as solutions in 1 ,3-butanediol.
  • Suitable vehicles and solvents that may be employed are water, saline, Ringer's solution, dextrose solution, isotonic sodium chloride solution, and Hanks' solution.
  • sterile, fixed oils are conventionally employed as solvents or suspending mediums.
  • any bland fixed oil may be employed including synthetic mono- or di-glycerides, corn, cottonseed, peanut, and sesame oil.
  • Fatty acids such as ethyl oleate, isopropyl myristate, and oleic acid and its glyceride derivatives, including olive oil and castor oil, especially in their polyoxyethylated versions, are useful in the preparation of injectables.
  • These oil solutions or suspensions may also contain long-chain alcohol diluents or dispersants.
  • the carrier may contain minor amounts of additives, such as substances that enhance solubility, isotonicity, and chemical stability, for example anti-oxidants, buffers and preservatives.
  • additives such as substances that enhance solubility, isotonicity, and chemical stability, for example anti-oxidants, buffers and preservatives.
  • the composition is formulated for administration by direct introduction to the lungs, such as by aerosol administration, by nebulized administration, by dry powder administration, or by being instilled into the lung. In some embodiments, it may be desirable to administer the composition directly to the airways in the form of an aerosol. Formulations for the administration of aerosol forms are known in the art.
  • the composition of the present invention may also be formulated using controlled release technology.
  • the composition may be administered as a sustained- release pharmaceutical.
  • the composition may be formulated with additional components such as vegetable oil (for example soybean oil, sesame oil, camellia oil, castor oil, peanut oil, rape seed oil); middle fatty acid triglycerides; fatty acid esters such as ethyl oleate; glycerol monooleate; polysiloxane derivatives; alternatively, water-soluble high molecular weight compounds such as hyaluronic acid or salts thereof (weight average molecular weight: ca. 80,000 to 2,000,000), carboxymethylcellulose sodium (weight average molecular weight: ca.
  • hydroxypropylcellulose viscosity in 2% aqueous solution: 3 to 4,000 cps
  • atherocollagen weight average molecular weight: ca. 300,000
  • polyethylene glycol weight average molecular weight: ca. 400 to 20,000
  • polyethylene oxide weight average molecular weight: ca. 100,000 to 9,000,000
  • hydroxypropylmethylcellulose viscosity in 1 % aqueous solution: 4 to 100,000 cSt
  • methylcellulose viscosity in 2% aqueous solution: 15 to 8,000 cSt
  • polyvinyl alcohol viscosity: 2 to 100 cSt
  • polyvinylpyrrolidone weight average molecular weight: 25,000 to 1 ,200,000.
  • the composition of the present invention may be incorporated into a hydrophobic polymer matrix, scaffold or support (such as a biodegradable matrix or support), including for controlled release of the composition over a period of days.
  • a hydrophobic polymer matrix, scaffold or support such as a biodegradable matrix or support
  • Methods for delivering agent(s) via scaffolds are known in the art.
  • a biomaterial scaffold including a scaffold produced from collagen, hydroxyapatite, ⁇ - tricalcium phosphate or a combination thereof may be used to deliver the agent.
  • Methods for incorporating agent(s) into such substrates are known in the art.
  • the composition may also be moulded into a solid implant, or externally applied patch, suitable for providing efficacious concentrations of the composition over a prolonged period of time without the need for frequent re-dosing.
  • controlled release films are well known in the art.
  • Other examples of polymers commonly employed for this purpose that may be used include nondegradable ethylene-vinyl acetate copolymer or degradable lactic acid-glycolic acid copolymers which may be used externally or internally.
  • Certain hydrogels such as poly(hydroxyethylmethacrylate) or poly(vinylalcohol) also may be useful, but for shorter release cycles than the other polymer release systems, such as those mentioned above.
  • the carrier may also be a solid biodegradable polymer or mixture of biodegradable polymers with appropriate time release characteristics and release kinetics.
  • the composition may then be moulded into a solid implant suitable for providing efficacious concentrations of the composition over a prolonged period of time without the need for frequent re-dosing.
  • the composition can be incorporated into the biodegradable polymer or polymer mixture in any suitable manner known to one of skill in the art and may form a homogeneous matrix with the biodegradable polymer, or may be encapsulated in some way within the polymer, or may be moulded into a solid implant.
  • the glycerolipid is present in the composition of the present invention in an amount ranging from one of the following selected ranges: 0.01 mg/g to 1 ,000 mg/g; 0.01 mg/g to 500 mg/g; 0.01 mg/g to 250 mg/g; 0.01 mg/g to 100 mg/g; 0.01 mg/g to 10 mg/g; 0.01 mg/g to 1 mg/g; 0.01 mg/g to 0.5 mg/g; 0.01 mg/g to 0.1 mg/g; 0.01 mg/g to 0.05 mg/g; 0.1 mg/g to 1 ,000 mg/g; 0.1 mg/g to 500 mg/g; 0.1 mg/g to 250 mg/g; 0.1 mg/g to 100 mg/g; 0.1 mg/g to 10 mg/g; 0.1 mg/g to 1 mg/g; 0.1 mg/g to 0.5 mg/g; 1 mg/g to 1 ,000 mg/g; 1 mg/g to 500 mg/g ; 1 mg/g to 250 mg/g; 1 mg/g
  • the antimicrobial agent is present in the composition of the present invention in an amount ranging from one of the following selected ranges: 0.1 ⁇ g/ml to 1 ,000 ⁇ g/ml, 1 ⁇ g/ml to 1 ,000 ⁇ g/ml, 10 ⁇ g/ml to 1 ,000 ⁇ g/ml, 100 ⁇ g/ml to 1 ,000 ⁇ g/ml, 500 ⁇ g/ml to 1 ,000 ⁇ g/ml, 0.1 ⁇ g/ml to 500 ⁇ g/ml, 1 ⁇ g/ml to 500 ⁇ g/ml, 1 0 ⁇ g/ml to 500 ⁇ g/ml, 1 00 ⁇ g/ml to 500 ⁇ g/ml, 0.1 ⁇ g/ml to 250 ⁇ g/ml, 1 ⁇ g/ml to 250 ⁇ g/ml, 10 ⁇ g/ml to 250 ⁇ g/ml, 1 00
  • composition of the present invention may be used to treat or prevent an infection in a subject.
  • the terms "treat”, “treating” or “treatment,” as used herein are to be understood to include within their scope obtaining a desired pharmacologic and/or physiologic effect in terms of improving the condition of the subject. This may be measured by one or more of the following non-limiting outcomes: (i) inhibiting to some extent the growth of a microorganism which is causing the infection in the subject, including, slowing down or complete growth arrest of the microorganism; (ii) inhibiting to some extent the growth and/or formation of one or more secondary microorganism infections in the subject; (iii) improving the life expectancy of the subject as compared to the untreated state; (iv) improving the quality of life of the subject as compared to the untreated state; (v) alleviating, abating, arresting, suppressing, relieving, ameliorating, and/or slowing the progression of at least one symptom caused by the microorganism infection in the subject; (vi) a partial or complete stabilization of the subject; (vii) a regression of
  • the terms "prevent” or “preventing” as used herein are to be understood to include within their scope obtaining a desired pharmacologic and/or physiologic effect in terms of arresting or suppressing the appearance of one or more symptoms in the subject. For example, inhibiting the formation of a microorganism infection in the subject.
  • the composition may be formulated so as to be applied to skin which has suffered a wound (for example a cut or abrasion), such that the composition acts to prevent microorganism infection in the cut or abrasion.
  • Suitable formulations have been described above and include topical creams, ointments, gels, and the like. Further details regarding wounds are provided below.
  • the subject will be resistant to the antimicrobial agent when the antimicrobial agent is administered in the absence of the glycerolipid.
  • a subject can be considered resistant to an antimicrobial agent when either the agent fails to treat or prevent a microorganism infection in the subject when administered in doses which have been considered safe, or when doses outside of those considered safe need to be administered to the subject to achieve the desired outcome.
  • the microorganism is a bacterium and therefore infection is due to a bacterium.
  • the bacterium comprises a Gram positive bacterium, a Gram negative bacterium, a Gram test non-responsive bacteria, an aerobic bacterium, or an anaerobic bacterium.
  • Examples of genera or species of bacterium include Abiotrophia, Achromobacter, Acidaminococcus, Acidovorax, Acinetobacter, Actinobacillus, Actinobaculum, Actinomadura, Actinomyces, Aerococcus, Aeromonas, Afipia, Agrobacterium, Alcaligenes, Alloiococcus, Alteromonas, Amycolata, Amycolatopsis, Anaerobe-spirillum, Anaerorhabdus, Arachnia, Arcanobacterium, Arcobacter, Arthrobacter, Atopobium, Aureobacterium, Bacteroides, Balneatrix, Bartonella, Bergeyella, Bifidobacterium, Bilophila Branhamella, Borrelia, Bordetella, Brachyspira, Brevibacillus, Brevibacterium, Brevundimonas, Brucella, Burkholderia, Buttiauxella, Buty
  • tuberculosis M. bovis, M. typhimurium, M. bovis strain BCG, BCG substrains, M. avium, M. intracellulare, M. africanum, M. kansasii, M. marinum, M. ulcerans, M. avium subspecies paratuberculosis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus aqui, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Listeria ivanovii, Bacillus anthracis, B.
  • subtilis Nocardia asteroides, Actinomyces israelii, Propionibacterium acnes, and Enterococcus species and Gram-negative bacteria such as Clostridium tetani, Clostridium perfringens, Clostridium botulinum, Pseudomonas aeruginosa, Vibrio cholerae, Actinobacillus pleuropneumoniae, Pasteurella haemolytica, Pasteurella multocida, Legionella pneumophila, Salmonella typhi, Brucella abortus, Chlamydi trachomatis, Chlamydia psittaci, Coxiella bumetti, Escherichia coli, Neiserria meningitidis, Neiserria gonorrhea, Haemophilus influenzae, Haemophilus ducreyi, Yersinia pestis, Yersinia enterolitica, Escherichia coli
  • the microorganism comprises a bacterium of the genus Staphylococcus, or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises Staphylococcus aureus or Staphylococcus epidermidis or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises methicillin-resistant Staphylococcus aureus (MRSA) and therefore the bacterial infection is due to MRSA.
  • MRSA methicillin-resistant Staphylococcus aureus
  • the microorganism comprises a bacterium of the genus Pseudomonas or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Pseudomonas aeruginosa or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises a bacterium of the genus Escherichia or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Escherichia coli or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises a bacterium of the genus Klebsiella or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Klebsiella pneumoniae or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises a bacterium of the genus Acinetobacter or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Acinetobacter baumannii or a small colony variant or antimicrobial resistant variant thereof.
  • the microorganism comprises a bacterium of the genus Enterococcus or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Enterococcus faecium or Enterococcus faecalis, or a small colony variant or antimicrobial resistant variant thereof.
  • biofilm is a cluster of bacterial cells, irreversibly attached to a surface and embedded in a matrix of extracellular polymeric substances self-produced by the bacteria.
  • Clinically relevant biofilms are often microbial complex structures associated with severe and recalcitrant diseases, including chronic wounds, cystic fibrosis, and chronic rhinosinusitis.
  • Staphylococcus aureus represents one of the most notorious bacteria causing invasive, superficial, chronic and nosocomial (including methicillin resistant S. aureus) infections.
  • biofilm state is advantageous for bacterial survival as the biofilm acts like a protective shield, enabling the bacteria to adapt to hostile environmental conditions, evade the immune system, and ultimately to establish resistance against antibacterial agents.
  • bacteria residing in biofilms can require up to 1000-fold higher concentrations of an antibacterial agent for their treatment than their planktonic (free-floating) counterparts. Therefore, bacterial biofilms represent one of the biggest challenges the medical community is facing. Indeed, recent data suggest that biofilms may account for over 80% of microbial infections in the body.
  • the bacterial infection forms part of a biofilm.
  • bacterial infections associated with biofilms include bacterial biofilms associated with urinary tract infections (e.g. E. coli, Pseudomonas aeruginosa, enterococci, Klebsiella, Enterobacter spp Proteus, Serratia), such as being responsible for persistent infections causing relapses and acute prostatitis, wounds including acute or chronic wounds (e.g. S. aureus, P. aeruginosa), lung infections (e.g. P. aeruginosa, such as occurs in patients with cystic fibrosis), chronic osteomyelitis (e.g. S. aureus), rhinosinusitis (e.g. S. aureus), tuberculosis (e.g. M. tuberculosis) and infections associated with foreign bodies inserted in the body (e.g. S. aureus).
  • urinary tract infections e.g. E. coli, P
  • the bacterial infection comprises an infected wound.
  • wounds include acute wounds (such as those caused by abrasions, cuts and more serious penetrative injuries, burns, abscesses, nerve damage and wounds resulting from elective surgery), chronic wounds (such as diabetic, venous and decubitus ulceration) or wounds in individuals with compromised wound healing capacity, such as the elderly.
  • the bacterial infection comprises a post-surgery infected wound, for example an infected wound following abdominal surgery or sinus surgery.
  • Methods for assessing bacterial infection are known in the art.
  • bacterial infection in a wound would delay healing of the wound.
  • various wound healing assays commonly known in the art could be utilised to test for assessing bacterial infection associated with wounds and healing thereof.
  • One such assay is the scratch wound assay where a "wound gap" in a cell monolayer (such as a fibroblast or keratinocyte monolayer) is created by scratching, and the "healing" of this gap by cell migration and growth towards the centre of the gap is monitored and often quantified.
  • Factors such as bacterial infection can alter the motility and/or growth of the cells which leads to a decreased rate of "healing" of the gap.
  • the microorganism is a fungus and therefore the infection is due to a fungus.
  • the antimicrobial agent is an antifungal.
  • composition suitable for administration to a subject comprising:
  • the glycerolipid potentiates the activity of the antifungal, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • fungal infections examples include infections associated with a fungal species such as Aspergillus, Alternaria, Aureobasidium, Candida, Cladosporium, Cryptococcus, Curvularia, Coniophora, Diplodia, Epidermophyton, Engodontium, Fusarium, Gliocladium, Gloeophylium, Humicola, Histoplasma, Lecythophora, Lentinus, Malassezia, Memnionella, Mucor, Oligoporus, Paecilomyces, Penicillium, Petriella, Paracoccidioides, Phanerochaete, Phoma, Pneumocystis, Poria, Pythium, Rhodotorula, Rhizopus, Schizophyllum, Sclerophoma, Scopulariopsis, Serpula, Sporobolomyces, Stachybotrys, Stemphylium, Trichosporon, Trichtoph
  • the infection may be due to a fungal skin or mucosal infection. In some embodiments, the fungal infection is due to Candida albicans.
  • the subject has become resistant to the antifungal when the antifungal is administered in the absence of the glycerolipid.
  • "Resistance" to the antifungal has the same meaning as set forth above.
  • an "antifungal” as used herein means a biocidal compound that can inhibit the growth of, or kill, fungi or fungal spores.
  • the antifungal may be selected from one or more of a polyene, an azole, an allylamine, and an echinocandin.
  • a polyene is a molecule with multiple conjugated double bonds.
  • a polyene antifungal is a rnacrocyclic polyene with a heavily hydro xylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic.
  • Polyene antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. As a result, the contents of the fungal ceil leak and result in cell death.
  • the polyene antifungal is selected from one or more of amphotericin B, candicidin, filipin, hamycin, natamycin, nystatin and rimocidin.
  • An azole antifungal can inhibit the enzyme lanosterol 14 ⁇ -demethylase, which is necessary to convert lanosterol to ergosterol. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of the membrane ultimately leading to inhibition of fungal growth.
  • the azole antifungal is selected from an imidazole, a triazole, and/or a thiazoie.
  • the imidazole may be selected from bifonazole, butoconazole, clotrimazole, econazole, fenticonazole, isoconazole, ketoconazole, Miconazole, miconazole, omoconazo!e, oxiconazole, sertaconazole, sulconazole and tioconazole.
  • the triazole may be selected from albaconazoie, efinaconazole, epoxyconazole, fluconazole, isavuconazole, itraconazole, posaconazole, propiconazole, ravuconazo!e, terconazole and voriconazole.
  • the thiazoie may include abafungin.
  • An al!y!amine can inhibit squalene epoxidase, which is another enzyme required for ergosterol synthesis in the fungal membrane, in some embodiments, the ally!amine antifungal may be selected from amorolfin, butenafine, naftifine, and terbinafine.
  • An echinocandin inhibits the synthesis of glucan in the cell wall via the enzyme 1 ,3- Beta-glucan synthase.
  • the echinocandin antifungal may be selected from anidulafungin, caspofungin and micafungin.
  • the antifungal for use in the composition of the present invention may also be selected from the group consisting of an aurone, benzoic acid, ciclopirox, flucytosine, griseofulvin, haloprogin, tolnaflate, undecylenic acid, crystal violet and Balsam of Peru.
  • the antifungal is selected from an azole and/or amphotericin B.
  • the term "subject" should be taken to encompass any subject which would benefit from administration of the composition of the present invention.
  • the subject is a human or animal subject.
  • the animal subject may be a mammal, a primate, a livestock animal (e.g. a horse, a cow, a sheep, a pig, or a goat), a companion animal (e.g. a dog, a cat), a laboratory test animal (e.g. a mouse, a rat, a guinea pig, a bird), an animal of veterinary significance, or an animal of economic significance.
  • composition of the present invention does not comprise a cationic surfactant.
  • the composition of the present invention has a pH in the physiological range of 5.5 (skin) to 7.35 (blood).
  • a composition comprising these two components can be used in a method for the treatment or prevention of an infection in a subject, a method for potentiating the activity of an antimicrobial agent in a subject, a method for reducing the dose of an antimicrobial agent required to treat or prevent an infection in a subject, or a method for increasing the potency of an antimicrobial agent required to treat or prevent an infection in a subject.
  • Other uses are contemplated.
  • the aforementioned methods require administering to the subject an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • Suitable glycerolipids and antimicrobial agents have already been described above, as too have the types of microorganisms causing infections that may be prevented or treated.
  • the term "effective amount” as used herein is the quantity of the composition which, when administered to a subject, improves the prognosis and/or health state of the subject with respect to their infection status.
  • the amount of composition to be administered to a subject will depend on the particular characteristics of one or more of the level or amount of resistance to the antimicrobial agent in the subject, the type of infection being inhibited, prevented or treated, the mode of administration of the composition, and the characteristics of the subject, such as general health, other diseases, age, sex, genotype, and body weight. A person skilled in the art will be able to determine appropriate dosages depending on these and other factors.
  • the effective amount of the composition to be used in the various embodiments of the present invention is not particularly limited.
  • the antimicrobial agent is administered to the subject (as part of the composition) so as to expose the microorganism causing the infection in the subject to a concentration of antimicrobial agent in the range from 0.1 ⁇ g/ml to 1 ,000 ⁇ g/ml, 1 ⁇ g/ml to 1 ,000 ⁇ g/ml, 10 ⁇ g/ml to 1 ,000 ⁇ g/ml, 100 ⁇ g/ml to 1 ,000 ⁇ g/ml, 500 ⁇ g/ml to 1 ,000 ⁇ g/ml, 0.1 ⁇ g/ml to 500 ⁇ g/ml, 1 ⁇ g/ml to 500 ⁇ g/ml, 10 ⁇ g/ml to 500 ⁇ g/ml, 100 ⁇ g/ml to 500 ⁇ g/ml, 0.1 ⁇ g/ml to 250 ⁇ g/ml, 1 ⁇ g/ml to 250 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising cefepime so as to expose the microorganism causing the infection in the subject to a concentration of cefepime in the range from 0.1 ⁇ g/ml to 1 28 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising gentamicin so as to expose the microorganism causing the infection in the subject to a concentration of gentamicin in the range from 0.1 ⁇ g/ml to 128 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising cefazoline so as to expose the microorganism causing the infection in the subject to a concentration of cefazoline in the range from 0.1 ⁇ g/ml to 1024 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising chloramphenicol so as to expose the microorganism causing the infection in the subject to a concentration of chloramphenicol in the range from 8.0 ⁇ g/ml to 128 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising vancomycin so as to expose the microorganism causing the infection in the subject to a concentration of vancomycin in the range from 0.5 ⁇ g/ml to 64 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising colistin so as to expose the microorganism causing the infection in the subject to a concentration of colistin in the range from 0.5 ⁇ g/ml to 16 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising tobramycin so as to expose the microorganism causing the infection in the subject to a concentration of tobramycin in the range from 16 ⁇ g/ml to 256 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising meropenem so as to expose the microorganism causing the infection in the subject to a concentration of meropenem in the range from 0.125 ⁇ g/ml to 128 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising bacitracin so as to expose the microorganism causing the infection in the subject to a concentration of bacitracin in the range from 2.0 ⁇ g/ml to 2,000 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising erythromycin so as to expose the microorganism causing the infection in the subject to a concentration of erythromycin in the range from 0.5 ⁇ g/ml to 256 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising ciprofloxacin so as to expose the microorganism causing the infection in the subject to a concentration of ciprofloxacin in the range from 0.25 ⁇ g/ml to 256 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising amikacin so as to expose the microorganism causing the infection in the subject to a concentration of amikacin in the range from 2.0 ⁇ g/ml to 126 ⁇ g/ml.
  • the aforementioned methods comprise administering to the subject a composition comprising chlorhexidine so as to expose the microorganism causing the infection in the subject to a concentration of chlorhexidine in the range from 0.025 ⁇ g/ml to 2.0 ⁇ g/ml.
  • the antimicrobial agent is administered to the subject (as part of the composition) in an amount ranging from one of the following selected ranges: 1 ⁇ g/kg to 1000 mg/kg; 1 ⁇ g/kg to 100 mg/kg; 1 ⁇ g/kg to 10 mg/kg; 1 ⁇ g/kg to 1 mg/kg; 1 ⁇ g/kg to 100 ⁇ g/kg; 1 ⁇ g/kg to 10 ⁇ g/kg; 10 ⁇ g/kg to 1000 mg/kg; 10 ⁇ g/kg to 100 mg/kg; 10 ⁇ g/kg to 10 mg/kg; 10 ⁇ g/kg to 1 mg/kg; 10 ⁇ g/kg to 100 ⁇ g/kg; 100 ⁇ g/kg to 1000 mg/kg; 100 ⁇ g/kg to 100 mg/kg; 100 ⁇ g/kg to 10 mg/kg; 100 ⁇ g/kg to 1 mg/kg; 1 mg/kg to 1000 mg/kg; 1 mg/kg to 100 mg/kg; 1 mg/kg to 100 mg/kg; 1 mg/kg; 1
  • the glycerolipid is administered to the subject (as part of the composition) so as to expose the microorganism causing the infection in the subject to a concentration of glycerolipid in the range from 0.01 mg/g to 1 ,000 mg/g; 0.01 mg/g to 500 mg/g; 0.01 mg/g to 250 mg/g; 0.01 mg/g to 100 mg/g; 0.01 mg/g to 10 mg/g; 0.01 mg/g to 1 mg/g; 0.01 mg/g to 0.1 mg/g ; 0.01 mg/g to 0.05 mg/g 0.1 mg/g to 1 ,000 mg/g; 0.1 mg/g to 500 mg/g; 0.1 mg/g to 250 mg/g; 0.1 mg/g to 100 mg/g; 0.1 mg/g to 10 mg/g; 0.1 mg/g to 1 mg/g; 0.1 mg/g to 0.5 mg/
  • the aforementioned methods comprise administering to the subject a composition comprising Capmul MCM so as to expose the microorganism causing the infection in the subject to a concentration of Capmul MCM in the range from 0.01 mg/g to 1 ,000 mg/g.
  • the glycerolipid is administered to the subject (as part of the composition) in an amount ranging from one of the following selected ranges: 0.01 ⁇ g kg to 100 mg/kg; 0.01 ⁇ g kg to 10 mg/kg; 0.01 ⁇ g/kg to 1 mg/kg; 0.01 ⁇ g kg to 100 ⁇ g/kg; 0.01 ⁇ g kg to 10 ⁇ g/kg; 0.01 ⁇ g kg to 1 ⁇ g/kg; 0.1 ⁇ g/kg to 100 mg/kg; 0.1 ⁇ g/kg to 10 mg/kg; 0.1 ⁇ g/kg to 1 mg/kg; 0.1 ⁇ g/kg to 100 ⁇ g/kg; 0.1 ⁇ g/kg to 10 ⁇ g/kg; 0.1 ⁇ g/kg to 1 ⁇ g/kg; 0.1 ⁇ g/kg to 100 ⁇ g/kg; 0.1 ⁇ g/kg to 10 ⁇ g/kg; 0.1 ⁇ g/kg to 1 ⁇ g/kg; 1 ⁇ g/kg; 1 ⁇ g/
  • the infection is a bacterial infection caused by Staphylococcus aureus.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, vancomycin, and chloramphenicol.
  • the present invention provides a method for the treatment or prevention of a Staphylococcus aureus infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, vancomycin, and chloramphenicol.
  • the infection is a bacterial infection caused by MRSA.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefepime, gentamicin, erythromycin, tobramycin, and ciprofloxacin.
  • the present invention provides a method for the treatment or prevention of a MRSA infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefepime, gentamicin, erythromycin, tobramycin, and ciprofloxacin.
  • the infection is a bacterial infection caused by Pseudomonas aeruginosa.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, cefepime, and tobramycin.
  • the present invention provides a method for the treatment or prevention of a Pseudomonas aeruginosa infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, cefepime, and tobramycin.
  • the infection is a bacterial infection caused by Escherichia coli.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and tobramycin.
  • the present invention provides a method for the treatment or prevention of an Escherichia coli infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and tobramycin.
  • the infection is a bacterial infection caused by Klebsiella pneumoniae.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and colistin.
  • the present invention provides a method for the treatment or prevention of a Klebsiella pneumoniae infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and colistin.
  • the infection is a bacterial infection caused by Acinetobacter baumannii.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of colistin, chloramphenicol, gentamicin, amikacin, and ciprofloxacin.
  • the present invention provides a method for the treatment or prevention of an Acinetobacter baumannii infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of colistin, chloramphenicol, gentamicin, amikacin, and ciprofloxacin.
  • the infection is a bacterial infection caused by Enterococcus faecium.
  • the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, meropenem, erythromycin, and bacitracin.
  • the present invention provides a method for the treatment or prevention of an Enterococcus faecium infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, meropenem, erythromycin, and bacitracin.
  • the infection is a bacterial infection caused by Staphylococcus epidermidis.
  • the glycerolipid is Capmul MCM and the antiseptic is chlorhexidine.
  • the present invention provides a method for the treatment or prevention of a Staphylococcus epidermidis infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antiseptic, wherein the glycerolipid is Capmul MCM and the antiseptic is chlorhexidine.
  • the infection is a bacterial infection caused by Enterococcus faecalis.
  • the glycerolipid is Capmul MCM and the antibiotic is tobramycin.
  • the present invention provides a method for the treatment or prevention of an Enterococcus faecalis infection in a subject, the method comprising administering to the subject a composition comprising a glycerolipid and an antibiotic, wherein the glycerolipid is Capmul MCM and the antibiotic is tobramycin.
  • the aforementioned methods may be used in treatment regimes that are beneficial for wound healing, treatment regimes that are beneficial for wound healing of an infected wound (such as that following surgery), treatment regimes that are beneficial for wound healing where the wound occurs during surgery or is a burn wound, treatment regimes that are beneficial for wound healing of chronic wounds, diabetic wounds and diabetic ulcers, treatment regimes that are beneficial for bacterial infections, including bacterial infections associated with a biofilm, and treatment regimes that are beneficial for fungal infections.
  • the present invention provides a method of treating an infected wound in a subject, the method comprising administering to the wound an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid, thereby treating the infected wound in the subject.
  • the method comprises topical administration of the composition.
  • the present invention provides a method of treating an infected wound in a subject, the method comprising topically administering to the wound an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid, thereby treating the infected wound in the subject.
  • the present invention provides a method of treating or preventing a bacterial infection of a wound, the method comprising administering to the wound an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid, thereby treating or preventing bacterial infection of the wound.
  • wounds are as described herein, such as a cut or abrasion, or a wound arising during surgery.
  • the method comprises topical administration of the composition.
  • the present invention provides a method of treating or preventing a bacterial infection of a wound, the method comprising topically administering to the wound a composition comprising a glycerolipid and an antibiotic or antiseptic, wherein the glycerolipid potentiates the activity of the antibiotic or antiseptic, wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid, thereby treating or preventing bacterial infection of the wound.
  • the present invention provides a method of reducing the viability of a microorganism, the method comprising exposing the microorganism to an effective amount of a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the present invention provides a method for reducing viability of a bacterium resistant to an antibiotic, the method comprising exposing the bacterium to an effective amount of a composition comprising a glycerolipid and an antibiotic or antiseptic, wherein the glycerolipid potentiates the activity of the antibiotic or antiseptic, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • microorganisms including bacteria and fungi
  • Methods for assessing the viability of microorganisms are known in the art. Exemplary microorganisms, including bacteria and fungi, are described above.
  • the microorganism is present in vitro.
  • the microorganism is present in a non-biological setting, such as being present in/on a device, a system, a container, a fluid, a surface, or a site.
  • a non-biological setting such as being present in/on a device, a system, a container, a fluid, a surface, or a site.
  • the aforementioned methods may be used to treat a medical device (such as an implant) or instrumentation, a surface, or to treat a water storage container or water pipes.
  • the microorganism may be present in or on an instrument, a medical device or an implant (which is potentially contaminated with a microorganism, such as a bacterium) for use in a subject and as such may need to be treated prior to use, so as to eliminate the microorganism and/or to reduce the likelihood of the subject becoming infected with the microorganism.
  • a microorganism such as a bacterium
  • instruments, medical devices or implants include, but are not limited to, catheters, intravenous catheters, vascular prosthesis, cerebrospinal fluid shunts, prosthetic heart valves, urinary catheters, joint prostheses and orthopaedic fixation devices, cardiac pacemakers, peritoneal dialysis catheters, intrauterine devices, biliary tract stents, dentures, breast implants, and contact lenses.
  • Such instruments, medical devices or implants may, for example, be treated with a composition comprising the glycerolipid and antimicrobial agent.
  • the glycerolipid may be combined with an antiseptic such as chlorhexidine for such applications.
  • surfaces which may be, or are, contaminated with a microorganism can be treated with a composition of the present invention to reduce or eliminate the microorganism thereby preventing subsequent transmission to a subject.
  • the glycerolipid may be combined with an antiseptic such as chlorhexidine for such applications.
  • an antiseptic such as chlorhexidine for such applications.
  • such a composition may be in the form a liquid which can be sprayed onto the surface to be treated.
  • Other formulations are contemplated as described above.
  • a "surface" encompasses any surface which may be exposed to the air and therefore exposed to a microorganism. Exemplary surfaces are those found in domestic settings, laboratory settings, hospitals, nursing homes, schools, childcare centres, and the like.
  • the present invention provides a method of treating an instrument, a medical device, an implant, or a surface, the method comprising exposing the instrument, medical device, implant, or surface, to a composition comprising a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • the microorganism is present in a biological setting. In some embodiments, the microorganism is present in vitro in a biological setting.
  • the microorganism is present in a biological system.
  • biological system refers to a cellular system and includes one or more cells in vivo, ex vivo, in vitro; a tissue or organ in vivo or ex vivo, or an entire subject.
  • the biological system comprises one or more cells in vitro, one or more cells in culture, one or more cells ex vivo, a tissue or organ, or a human or animal subject.
  • the microorganism is present in vivo. In some embodiments, a subject is infected with the microorganism.
  • the aforementioned methods are used to reduce the viability of one or more microorganisms. In some embodiments, the methods are used to kill one or more microorganisms.
  • the methods reduce the viability of the microorganisms by 50% or more, by 60% or more, by 70% or more, by 80% or more, by 90% or more, by 95% or more, by 99% or more, by 99.9% or more, by 99.99% or more, or by 99.999% or more.
  • the methods comprise reducing the viability of the microorganism by 10 fold or more, by 100 fold or more, by 1000 fold or more, by 10 4 fold or more, by 10 5 fold or more, or by 10 6 fold or more. Other levels of reduction of viability are contemplated.
  • the methods substantially kill all the microorganisms. In some embodiments, the methods reduce the viability of microorganisms to below detectable levels. In some embodiments, the methods reduce the viability of microorganisms to below a clinically relevant level.
  • exposing refers to directly and/or indirectly contacting and/or treating a microorganism with a glycerolipid and an antimicrobial agent.
  • a microorganism may be exposed directly, but separately, to the glycerolipid and the antimicrobial agent, or may be exposed to a composition comprising the glycerolipid and the antimicrobial agent.
  • the microorganism may, for example, be exposed to the glycerolipid and the antimicrobial agent directly, but separately, or exposed to a composition comprising the glycerolipid and the antimicrobial agent, such as a liquid composition.
  • the microorganism may for example be exposed to the glycerolipid and the antimicrobial agent directly or indirectly, such as a tissue or organ being perfused with a composition comprising the glycerolipid and the antimicrobial agent.
  • the microorganism may for example be exposed to the glycerolipid and the antimicrobial agent directly or indirectly, either separately or in the form of a composition comprising the glycerolipid and the antimicrobial agent, for example such as by topical application directly to a site of infection.
  • kits may comprise the composition of the invention, the individual components of the composition, and/or instructions for performing a method described herein.
  • the kit may be used for the treatment or prevention of an infection in a subject.
  • the kit comprises a glycerolipid and an antimicrobial agent, wherein the glycerolipid potentiates the activity of the antimicrobial agent, and wherein the triglyceride content of the glycerolipid is ⁇ 10% w/w of the total glyceride content of the glycerolipid.
  • Suitable glycerolipids, antibiotics and exemplary microorganisms that cause infection are described above.
  • the glycerolipid and antimicrobial agent are provided as separate components of the kit, and the kit includes instructions for mixing the components in defined amounts to treat or prevent the infection.
  • the glycerolipid and antimicrobial agent are provided already combined as a single composition.
  • the kit may again include instructions for administering the composition in defined amounts to treat or prevent the infection.
  • the kit may include instructions for suitable operational parameters in the form of a label or separate insert.
  • the purpose of the present study was to explore the interaction of glycerolipids and antibiotics and to investigate potential synergistic effects against planktonic and biofilm-associated bacteria.
  • the antimicrobial effects of individual compounds and antibiotic/glycerolipid combinations were tested against four ESKAPE pathogens ⁇ Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae) that are responsible for the majority of nosocomial infections.
  • Mueller Hinton broth was purchased from Becton-Dickinson (BD, Wayville, SA, Australia) and was used as growth medium unless noted differently.
  • Mueller Hinton agar and Tryptic soy agar were purchased from BD, and AlamarBlue Cell Viability Reagent was purchased from ThermoFisher Scientific (Adelaide, SA, Australia).
  • Glycerol monocaprylocaprate Type I Capmul MCM EP/NF; Imwitor 742
  • glycerol monocaprylate Type I (Imwitor 988) were a gift from Abitec (Janesville, Wl, USA) and 101 Oleo GmbH (Witten, Germany), respectively.
  • Gentamicin, cefepime, cefazolin, and sodium chloride were of analytical-grade and purchased from Sigma-Aldrich (Castle Hill, NSW, Australia). High purity water was obtained from a Milli-Q purification system (Millipore, Billerica, MA, USA).
  • ESKAPE pathogens were selected for susceptibility testing: Staphylococcus aureus (clinical isolate SA CM ); methicillin resistant Staphylococcus aureus (clinical isolate, MRSA CM ); methicillin resistant Staphylococcus aureus (MRSA) ATCC 33591 ; Pseudomonas aeruginosa (P. aeruginosa, clinical isolate PA CM ); Escherichia coli (E.coli) ATCC 1 1229; and Klebsiella pneumoniae (K. pneumoniae) ATCC 700603.
  • ESKAPE pathogens were obtained from either the American Type Culture Collection (ATCC) (Manassas, Virginia, USA) or as clinical isolates (CI) from SA Pathology (Frome Road, Sydney, South Australia 5000, Australia).
  • the minimum inhibitory concentration (MIC) was determined by the broth microdilution method as described previously (for example, see Wiegand I et al, 2008, Nature Protocols, 3(2): 163-175, and (CLSI), C.a.L.S.I., Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 2012, Wayne, PA, USA). Single colonies from a fresh streak-out plate were suspended in sterile saline and adjusted to an absorbance (OD 600 ) of 0.10 ⁇ 0.02, corresponding to a cell density of 1 -2 x 10 8 colony forming units (CFU)/mL .
  • OD 600 absorbance
  • a 1 in 100 dilution of the bacterial suspension in suitable medium was prepared and thoroughly mixed in a sterile tube and served as inoculum.
  • the bacterial suspension was used within 30 minutes of preparation.
  • the wells of a clear, sterile flat bottom 96-well microtiter plate (Greiner bio- one, Interpath, Heidelberg, VIC, Australia) were filled with inoculum, sterile broth, and antibiotic as shown in Figure 1 .
  • Samples (10 ⁇ L_) of the final positive control (wells in column 1 1 ) were verified for cell density (target 5 x 10 5 CFU/mL) by suitable dilution in broth and plating onto 2 agar plates. Following incubation for 16-20 h at 37°C the colonies were counted.
  • the fractional inhibitory concentration index (FICI) for the combination of each antibiotic and glycerolipid was calculated using the checkerboard method (Sopirala MM et al., 2010, Antimicrobial Agents and Chemotherapy, 54(1 1 ): 4679-4683).
  • the formula FICA + FICB FICI was calculated (where FICA denotes the MIC of compound A in combination divided by the MIC of compound A alone; and FICB denotes the MIC of compound B in combination divided by the MIC of compound B alone).
  • Synergy was defined as FICI ⁇ 0.5, additive effects as 0.5 ⁇ FICI ⁇ 1 ; indifference as 1 ⁇ FICI ⁇ 4, and FICI >4 denoted antagonism.
  • Biofilms were grown on the bottom of microtiter plates as described previously (Thomas N et al., 2015, J. Materials Chem. B, 3(14): 2770-2777; and Peeters E et al., 2008, Microbiological Methods, 72(2): 157-165).
  • An overnight culture was adjusted to a cell density of 1 -2 x 10 8 CFU/mL, diluted 1/15 with broth and then 100 ⁇ were added to the wells of a black 96 well plate (Greiner bio-one). The outer wells of the plate were filled with sterile PBS to prevent evaporation of the inner wells.
  • the percentage of biofilm killing (BK) after exposure to combinations of antibiotics and lipids was calculated from the fluorescence intensities (Fl) of unexposed (control) biofilms and biofilms exposed to antibiotics/lipids according to Equation 1 below (Thomas N et al., 2015, supra).
  • MBIC biofilm inhibitory concentration
  • the MICs and MBICs of the tested antibiotics and glycerolipids are summarised in Table 1 .
  • the MBIC was increased compared to the MIC.
  • the MIC of cefepime in PA CM was 2 mg/L
  • the corresponding MBIC increased 64-fold to 128 mg/L.
  • the reduced susceptibility towards antimicrobials has been related to the reduced metabolic activity of biofilm-associated bacteria.
  • the bacteria are encased in an extracellular matrix that protects the bacteria from antimicrobials by reducing their penetration through the matrix or by increased exposure to enzymes (e.g. ⁇ -lactamase) resulting in reduced exposure to antimicrobials.
  • the MBIC was typically higher compared to the MIC for antibiotics, the MICs and MBICs of glycerolipids were comparable, with the exception of the MRSA clinical isolate for which a much higher MBIC was observed.
  • the MICs of the tested mono/diglycerides were substantially lower in Gram-positive bacteria (S. aureus/MRSA) compared to Gram-negative species, in particular in P. aeruginosa and K. pneumoniae.
  • the tested mono/diglycerides showed comparable antimicrobial activity irrespective of their composition (i.e. fatty acid chain length and mono/diglyceride ratios). Different concentrations were however required against S. aureus ( ⁇ 1 mg/mL) and E. coli ( ⁇ 8 mg/mL).
  • Capmul MCM EP/NF contains 45-75% monoacylglycerols (60.1 % in the batch used in the present study), 20-50% diacyclglycerols (32.9% in the batch used in the present study), and ⁇ 10% triacylglycerols (5% in the batch used in the present study). Furthermore, Capmul MCM EP/NF contains 50-90% caprylic acid (83.2% in the batch used in the present study), 10-50% of capric acid (16.8% in the batch used in the present study) and ⁇ 3% of lauric acid (0% in the batch used in the present study).
  • Imwitor 742 contains 45-75% monoacylglycerols (59% in the batch used in the present study), 20-50% diacyclglycerols (34% in the batch used in the present study), and ⁇ 10% triacylglycerols (6% in the batch used in the present study). Furthermore, Imwitor 742 contains 50-90% caprylic acid (57.7% in the batch used in the present study), 10-50% of capric acid (41 .9% in the batch used in the present study) and ⁇ 3% of lauric acid (0.21 % in the batch used in the present study).
  • Imwitor 988 contains 45-75% monoacylglycerols (50% in the batch used in the present study), 20-50% diacyclglycerols (39.4% in the batch used in the present study), and ⁇ 10% triacylglycerols (8% in the batch used in the present study). Furthermore, Imwitor 988 contains a minimum of 90% caprylic acid (99.1 % in the batch used in the present study), a maximum of 10% capric acid (-1 % in the batch used in the present study), and a maximum of 1 % lauric acid (less than 0.1 % in the batch used in the present study).
  • the observed enhanced antimicrobial effects of antibiotic/glycerolipid combinations could be: i) the improved penetration of antibiotics through the cell membranes of bacteria facilitated by surface-active mono/diglycerides; ii) destabilisation of the bacterial cell membrane; iii) enhanced transporter-mediated uptake of antibiotics; iv) interference with metabolic activity increasing antibiotic susceptibility; v) interference with the quorum sensing system of biofilms; and vi) interference with the production of biofilm matrix components.
  • Example 1 The studies described above in Example 1 were extended to include the testing of additional bacterial strains against further glycerolipid/antibiotic combinations. For these extended studies, minimum inhibitory concentrations (MIC), minimum biofilm inhibitory concentrations (MBIC) and synergy assays (checkerboard design) were carried out using the same methods as described in Example 1 .
  • MIC minimum inhibitory concentrations
  • MBIC minimum biofilm inhibitory concentrations
  • synergy assays checkerboard design
  • a number of bacterial strains and eight antibiotics (comprising various classes of systemically used antibiotics) were combined and assessed for their antimicrobial effects against both planktonic and biofilm bacteria. Treatment of the bacterial strains was conducted with antibiotics alone, or in combination with the mono/diglyceride Capmul MCM.
  • ESKAPE bacterial strains tested were methicillin resistant Staphylococcus aureus (MRSA) ATCC 33591 strain, Acinetobacter baumanii clinical isolate CI 1 ; Escherichia coli clinical isolate CI 8, Klebsiella pneumoniae ATCC 700603 strain, Enterococcus faecium ATCC 19434 strain, and Pseudomonas aeruginosa clinical isolate CI ML.
  • ESKAPE strains were obtained from either the American Type Culture Collection (ATCC) (Manassas, Virginia, USA) or as clinical isolates (CI) from SA Pathology (Frome Road, Sydney, South Australia 5000, Australia).
  • the antibiotics tested included chloramphenicol, gentamicin, vancomycin, colistin, tobramycin, cefazolin, meropenem, and cefepime.
  • the antibiotics were obtained from Sigma-Aldrich (Castle Hill, NSW, Australia).
  • Assays were carried out in 96 well plates. MICs were assessed both visually and by plate reading (OD 600 ), and anti-biofilm effects (24 hour old biofilms) were quantified by AlamarBlue and fluorescence measurements. In all cases bacteria were exposed for 24 hours to the respective treatments. All experiments were carried out at least as 2 technical and 2 biological replicates (MIC/MBIC), and checkerboard as biological replicates (2 different days).
  • the ESKAPE bacterial strains tested were Escherichia coli ATCC 1 1229 strain, Enterococcus faecalis ATCC 29212 strain, Klebsiella pneumoniae ATCC 700603 strain, Enterococcus faecium ATCC 19434 strain, Acinetobacter baumannii ATCC 19606 strain, Staphylococcus aureus (MRSA) ATCC 33591 strain, Enterococcus faecium clinical isolate CI 1 , Enterococcus faecalis clinical isolate CI 2, Staphylococcus aureus (MRSA) clinical isolates CI Ba, CI Ru, and CI Se, Acinetobacter baumannii clinical isolates CI 17 and CI 19, and Pseudomonas aeruginosa clinical isolates CM 8 and CI Ma.
  • ESKAPE pathogens were obtained from either the American Type Culture Collection (ATCC) (Manassas, Virginia, USA) or as clinical isolates (CI) from SA Pathology (Frome Road, Sydney, South Australia 5000, Australia).
  • ATCC American Type Culture Collection
  • CI clinical isolates
  • SA Pathology Frome Road, Sydney, South Australia 5000, Australia.
  • MIC minimum inhibition concentration
  • the screening also included Staphylococcus epidermidis ATCC 35984 and 14990 strains (not an ESKAPE pathogen) as it is an important opportunistic pathogen causing hospital acquired infections (e.g. catheter infections).
  • the S. epidermidis strains were tested against the antiseptic chlorhexidine.
  • the antibiotics tested included, gentamicin, tobramycin, colistin, bacitracin, erythromycin, ciprofloxacin, and amikacin. Note that gentamicin, tobramycin, and colistin are used both systemically and topically.
  • the antibiotics and chlorhexidine were obtained from Sigma-Aldrich (Castle Hill, NSW, Australia).
  • the bacteria count following extraction from the dermis after 24 hour treatment indicated a colony count (CFU) as high as 1 X10 9 (untreated dermis), while an extremely high gentamicin (64 ug/MI) concentration (i.e. too high for administration to humans) were required to reduce the CFU 10-fold to approximately 1 X10 8 .
  • a comparable effect (P ⁇ 0.05) was, however, achieved when using a combination of gentamicin (2 ug/MI) plus Capmul (2 mg/MI), demonstrating the ability of Capmul to dramatically reduce the antibiotic concentration relative to administration of the antibiotic alone. This further evidences the effectiveness of the antibiotic/glycerolipid combination for therapeutic applications in subjects.
  • Full thickness excisional wound models in an animal are performed to assess the efficacy of antibiotic/glycerolipid or antiseptic/glycerolipid combinations in treating bacterial infection.
  • One such model is the punch biopsy assay performed for example in rats.
  • a 6 mm biopsy punch is used to create an excisional wound on the back of a rat.
  • a pair of scissors and/or a scalpel blade is used to aid in the removal of skin if necessary.
  • a piece of dry sterile gauze is placed on each wound to absorb excess blood.
  • 50 ⁇ L_ of a bacterial suspension to be tested (5 x 10 7 CFU/mL) is instilled into each wound and allowed to absorb for 1 -2 minutes. After inoculation the wound site is covered with Tegaderm (3M Australia), and then wrapped using Vetrap® (3M Australia) or equivalent. This facilitates the development of a bacterial biofilm (i.e. bacteria embedded in a slime) reflecting the hallmarks of a chronic infection, characterized by a high bacterial burden and treatment recalcitrance.
  • compositions of the present invention comprising antimicrobial agent/glycerolipid combinations
  • Exemplary models are provided below.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the eyes can be performed using ex vivo rabbit and human corneas as described in Pinnock A et al., 2017, Graefe's Arch. Clin. Exp. Ophthalmol., 255 (2): 333-342.
  • Exemplary formulations for treating sites of infection in the eyes include eye drops in the form of a solution or emulsion suitable for use during the day, and a cream or ointment for night application. Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the ears can be performed using a rat model for outer ear infection (for example see Emgard P and Hellstrom S, 1997, Eur. Arch. Otorhinolaryngol., 254(3): 1 15-1 19), or a mouse model for middle ear infection (for example see Melhus A and Ryan AF, 2003, APMIS, 1 1 1 (10): 989-994).
  • exemplary formulations for treating sites of infection in the ears include ear drops in the form of a solution or emulsion, gels, creams and ointments. Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the nose or sinuses can be performed using various sheep models. See for example, Ha KR et al., 2007, Am. J. Rhinol., 21 (3): 339-345; Drilling A et al., 2014, International forum of allergy & rhinology, 4(3): 176-186; and Jardeleza C et al., 2015, Transl. Res., 166(6): 683- 692.
  • Exemplary formulations for treating sites of infection in the nose and sinuses include drops, emulsions, or other solutions which can be squirted into the sinuses (such as nebulizer or spray-type formulations). Other formulations are contemplated as described above.
  • a number of animal models can be used to assess antimicrobial agent/glycerolipid compositions of the present invention for treating infection of skin and soft tissue. With respect to abscesses, assays outlined in Mansour SC et al., 2016, EBioMedicine, 12: 219- 226, or Avci P et al., 2013, Expert Opinion on Drug Discovery, 8(3): 331 -355, may be used.
  • Exemplary formulations for treating sites of infection as a result of an abscess include disinfecting soap or solution following surgical cut and draining of pus, and an emulsion or lotion once the cut is closed. Other formulations are contemplated as described above. With respect to acne, an assay outlined in Jang Y H et al., 2015, Annals of Dermatology, 27(3): 257-264 may be used. Exemplary formulations for treating acne- based infection include topical ointments, creams, gels, solutions, emulsions, and the like. Other formulations are contemplated as described above. With respect to wounds, a number of animal models can be utilised as reviewed in Kopecki W et al., 2017, supra).
  • Exemplary formulations for treating sites of infection as a result of a wound include ointments, creams, gels, solutions, emulsions, and the like. Other formulations are contemplated as described above. With respect to the treatment of nail infections, appropriate assays include the rabbit model of onchomycosis described in Shimamura T et al., 201 1 , Antimicrob. Agents Chemother., 55(7): 3150-3155. Exemplary formulations for treating nail infections include topical formulations in the form of gels, creams, pastes, or other liquid formulations that can be incorporated into nail polish or lacquer. Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the lungs can be performed using various rodent pneumonia models such as those described in McConnell MJ et al., 2013, FEMS Microbiol. Rev., 37(2): 130-155; and Mizgerd JP and Skerrett SJ, 2008, Am. J. Physiol. Lung Cell. Mol. Physiol., 294(3): L387-398.
  • Exemplary formulations for treating sites of infection in the lungs include dry powder formulations or liquid formulations administered via a nebulizer. Other formulations are contemplated as described above.
  • compositions of the present invention for treating infection of the bones can be performed using a rodent model of osteomyelitis such as that described in Orhan Z et al., 2006, Journal of Bone & Joint Surgery, British Volume, 88-B(2): 270-275.
  • exemplary formulations for treating sites of infection in bones include polymeric or lipid nano/microparticles; silica or polymer lipid hybrid particles (SLH/PLH; Solid lipid nanoparticles (SLN), or Bone cement (surgery/implant). Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the bladder can be performed using a murine model as described in Hannan TJ et al., 2016, Methods Mol. Biol., 1333: 159-175.
  • Exemplary formulations for treating sites of infection in the bladder include liquid installation solutions/emulsions. Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the vagina can be performed using a murine model described in Gilbert NM et al., 2013, PLoS ONE, S(3): e59539.
  • Exemplary formulations for treating sites of infection in the vagina include suppositories or pessaries. Other formulations are contemplated as described above.
  • Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the large intestine can be performed using a number of animal models such as those described in Best EL et al., 2012, Gut Microbes, 3(2): 145-167.
  • Exemplary formulations for treating sites of infection in the large intestine include oral formulations (such as tablets or capsules) that are coated so as to open in the large intestine. Other formulations are contemplated as described above.
  • compositions of the present invention for treating or preventing infections in the mouth can be performed on suitable subjects.
  • exemplary formulations include antiseptic mouthwashes, sprays, lozenges, this films and the like. Other formulations are contemplated as described above.
  • An antimicrobial agent/glycerolipid composition of the present invention may be prepared by combining a therapeutically effective amount of the antimicrobial agent with the glycerolipid. Suitable amounts of the antimicrobial agent have been described above.
  • the composition may then be administered in an appropriate formulation to a subject suffering from a microorganism infection such as a bacterial infection.
  • the dose and timing of administration may be selected by a medical practitioner based on the nature, location and severity of the infection to be treated, and taking into account the various patient characteristics.
  • An appropriate formulation for the composition is also based on the nature and location of the infection to be treated. Subjects are monitored following administration. Effectiveness of the composition is evaluated by analysis of infection retraction.

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Abstract

L'invention concerne des compositions antimicrobiennes et des procédés pour leur utilisation. En particulier, les compositions comprennent un glycérolipide, tel que Capmul MCM, Imwitor 742 ou Imwitor 988, et un agent antimicrobien, le glycérolipide potentialisant l'activité de l'agent antimicrobien. Les agents antimicrobiens selon la présente invention comprennent des antibiotiques, des antiseptiques et des antifongiques. Les compositions antimicrobiennes de la présente invention peuvent être utilisées pour le traitement ou la prévention d'une infection, telle qu'une infection bactérienne ou fongique, ou pour réduire la viabilité d'un micro-organisme, tel qu'une bactérie. La présente invention concerne également des procédés pour potentialiser l'activité d'un agent antimicrobien, pour réduire la dose d'un agent antimicrobien nécessaire pour traiter ou prévenir une infection ou pour augmenter la puissance d'un agent antimicrobien requis pour traiter ou prévenir une infection, par l'administration d'une composition antimicrobienne décrite dans la description. La présente invention concerne également des kits comprenant la composition antimicrobienne.
PCT/AU2018/050907 2017-08-24 2018-08-24 Compositions antimicrobiennes et procédés d'utilisation WO2019036770A1 (fr)

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CN112791048A (zh) * 2020-12-31 2021-05-14 海南海神同洲制药有限公司 一种硝酸舍他康唑栓及其制备方法
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220117859A1 (en) * 2018-11-30 2022-04-21 3M Innovative Properties Company Topical antimicrobial microemulsions with fluorescent materials
CN112791048A (zh) * 2020-12-31 2021-05-14 海南海神同洲制药有限公司 一种硝酸舍他康唑栓及其制备方法

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