WO2019036770A1

WO2019036770A1 - Antimicrobial compositions and methods of use

Info

Publication number: WO2019036770A1
Application number: PCT/AU2018/050907
Authority: WO
Inventors: Nicky Dieter THOMAS; Katharina Richter; Clive Allan Prestidge
Original assignee: University of South Australia
Current assignee: Adelaide University
Priority date: 2017-08-24
Filing date: 2018-08-24
Publication date: 2019-02-28
Anticipated expiration: 2020-02-24

Abstract

The present invention relates to antimicrobial compositions and methods for their use. In particular, the compositions comprise a glycerolipid, such as Capmul MCM, Imwitor 742, or Imwitor 988, 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. Antimicrobial compositions encompassed by the present invention can be used for the treatment or prevention of an infection, such as a bacterial or fungal infection, or for reducing the viability of a microorganism, such as a bacterium. The present invention also relates to methods for potentiating the activity of an antimicrobial agent, for reducing the dose of an antimicrobial agent required to treat or prevent an infection, or for increasing the potency of an antimicrobial agent required to treat or prevent an infection, by administering an antimicrobial composition described herein. Kits comprising the antimicrobial compositions are also encompassed by the present invention.

Description

ANTIMICROBIAL COMPOSITIONS AND METHODS OF USE

PRIORITY CLAIM

[0001 ] This application claims priority from Australian provisional patent application number 2017903421 filed on 24 August 2017, the contents of which are to be taken as incorporated herein by this reference.

FIELD OF THE INVENTION

[0002] The present invention relates generally to antimicrobial compositions and methods for their use. In particular, 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.

BACKGROUND OF THE INVENTION

[0003] 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. Furthermore, antiseptics are typically used to reduce or prevent the possibility of infection, sepsis, or putrefaction caused by microorganisms.

[0004] Since the discovery of penicillin in 1928 by Alexander Fleming, and its subsequent purification and development as an antibacterial agent, antibiotics have underpinned modern medicine. In fact, their use has been indispensable for the treatment of serious infections such as tuberculosis, meningitis and pneumonia, for preventing surgical site infections, and for managing immunocompromised individuals.

[0005] However, it was not long after penicillin was introduced as an antibacterial to the mass population that resistance to the antibiotic was recognised. In fact it was Fleming himself that warned the "thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin- resistant organism". This is not limited to penicillin. Indeed infectious microorganisms have become increasingly resistant to the existing arsenal of antibiotic drugs, including resistance to all first-line and last-resort antibiotics.

[0006] The most recent World Economic Forum Global Risks reports have listed antibiotic resistance as one of the greatest global threats to humanity and global health systems. For example, it is estimated that antimicrobial resistance is responsible for 23,000 deaths annually in the United States, more than 25,000 in Europe, and 700,000 globally. According to a recent report commissioned by the UK government this number is expected to rise up to 10 million deaths per year by 2050. The associated economic cost is staggering with a current estimated 21 to 34 billion dollar burden to the United States alone each year.

[0007] However, despite the clear need for new antibiotics or new antimicrobial-based treatments, the development pipeline is currently thin. This is in part due to the need to identify antibacterial agents that act via novel mechanisms in order to effectively address the current drug resistance issues. According to one estimate, twenty novel classes of drugs are required for antibiotics to be working effectively for the next fifty years. The other factor to the constrained antibiotic development pipeline is the aversion of pharmaceutical and biotechnology companies to invest in the required research and development due to the short term that these treatments are typically administered. Furthermore, the return on investment is low given that newly developed drugs are considered as last resort therapy.

[0008] Apart from identifying antibacterial agents that act via novel mechanisms, several other strategies have been pursued to mitigate the antibiotic resistance issue. These have included bacteriophage therapy, re-purposing of already approved drugs with a different indication, re-formulation of marketed antibiotics and antiseptics to improve their effectivity, and the use of antibiotic peptides. However, while some of these approaches have shown promising results in vitro, numerous hurdles (in particular safety and regulatory) have to be overcome before entering the market.

[0009] Accordingly, there is a clear need to address the issue of antibiotic resistance in the face of global health concerns. Furthermore, there is a clear need for antimicrobial compositions that display enhanced activity over existing antimicrobial formulations, including the need for antimicrobial compositions that enable a reduction in the amount of antimicrobial agent delivered to achieve a desired outcome.

[0010] The discussion of documents, acts, materials, devices, articles and the like is included in this specification solely for the purpose of providing a context for the present invention. It is not suggested or represented that any or all of these matters formed part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

SUMMARY OF THE INVENTION

[0011 ] 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.

[0012] Accordingly, in a first aspect, the present invention provides a composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) 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.

[0013] In some embodiments, 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.

[0014] In some embodiments, 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.

[0015] In some embodiments, the glycerolipid comprises only medium chain length fatty acids. In some embodiments, the medium chain length fatty acids comprise caprylic acid. In some embodiments, 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.

[0016] In some embodiments, the medium chain length fatty acids comprise capric acid. In some embodiments, 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.

[0017] In some embodiments, the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.

[0018] In some embodiments, the antimicrobial agent is selected from an antibiotic, an antiseptic, and an antifungal.

[0019] In some embodiments, 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.

[0020] In some embodiments, the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.

[0021 ] In some embodiments, the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.

[0022] In some embodiments, the antiseptic is chlorhexidine.

[0023] In some embodiments, the antifungal is selected from an azole and/or amphotericin B.

[0024] In some embodiments, 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.

[0026] In some embodiments, the glycerolipid potentiates the activity of the antimicrobial for the treatment or prevention of an infection in the subject. In some embodiments, the subject has become resistant to the antimicrobial when administered in the absence of the glycerolipid.

[0027] In some embodiments, the infection is a bacterial infection. In some embodiments, the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis. In some embodiments, the bacterial infection is due to MRSA.

[0028] In some embodiments, the bacterial infection forms part of a biofilm. In some embodiments, the bacterial infection comprises an infected wound.

[0029] In some embodiments, the infection is a fungal infection. In some embodiments, the fungal infection is due to Candida albicans.

[0030] In some embodiments, the subject is a human or an animal.

[0031 ] In a second aspect, 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.

[0032] In some embodiments of the second aspect of the present invention, 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.

[0034] In some embodiments of the second aspect of the present invention, the glycerolipid comprises only medium chain length fatty acids. In some embodiments, the medium chain length fatty acids comprise caprylic acid. In some embodiments, 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.

[0035] In some embodiments of the second aspect of the present invention, the medium chain length fatty acids comprise capric acid. In some embodiments, 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.

[0036] In some embodiments of the second aspect of the present invention, the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.

[0037] In some embodiments of the second aspect of the present invention, the antimicrobial agent is selected from an antibiotic, an antiseptic, and an antifungal.

[0038] In some embodiments of the second aspect of the present invention, 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.

[0039] In some embodiments of the second aspect of the present invention, the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol. [0040] In some embodiments of the second aspect of the present invention, the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.

[0041 ] In some embodiments, the antiseptic is chlorhexidine.

[0042] In some embodiments, the antifungal is selected from an azole and/or amphotericin B.

[0043] In some embodiments of the second aspect of the present invention, the composition is in the form of a liquid, gel, paste, cream, powder, or aerosol.

[0044] In some embodiments of the second aspect of the present invention, the composition is topically administered to the subject.

[0045] In some embodiments of the second aspect of the present invention, the infection has become resistant to the antimicrobial when administered in the absence of the glycerolipid.

[0046] In some embodiments of the second aspect of the present invention, the infection is a bacterial infection. In some embodiments, the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis. In some embodiments, the bacterial infection is due to MRSA.

[0047] In some embodiments of the second aspect of the present invention, the bacterial infection forms part of a biofilm. In some embodiments, the bacterial infection comprises an infected wound.

[0048] In some embodiments of the second aspect of the present invention, the infection is a fungal infection. In some embodiments, the fungal infection is due to Candida albicans.

[0049] In some embodiments of the second aspect of the present invention, the subject is a human or an animal. [0050] In a third aspect, 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.

[0051 ] In a fourth aspect, 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:

(i) a glycerolipid; and

(ii) an antimicrobial agent,

[0052] In a fifth aspect, 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.

[0053] In a sixth aspect, 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.

[0054] In a seventh aspect, 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.

[0055] In an eighth aspect, 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.

[0056] In a ninth aspect, 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.

[0057] In a tenth aspect, 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.

[0058] In an eleventh aspect, 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.

[0059] In a twelfth aspect, 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. [0060] In a thirteenth aspect, 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.

[0061 ] In a fourteenth aspect, 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.

[0062] In a fifteenth aspect, 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.

[0063] In a sixteenth aspect, 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.

[0064] In a seventeenth aspect, 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.

[0065] In an eighteenth aspect, 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. [0066] In a nineteenth aspect, 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.

[0067] In a twentieth aspect, 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.

[0068] In a twenty first aspect, 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.

[0069] In a twenty second aspect, 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.

BRIEF DESCRIPTION OF THE FIGURES

[0070] For a further understanding of the aspects and advantages of the present invention, reference should be made to the following detailed description, taken in conjunction with the accompanying figures which illustrate certain embodiments of the present invention.

[0071 ] FIGURE 1 - is a schematic of the microdilution method used for determination of the minimum inhibitory concentration (MIC) of various bacterial strains.

[0072] FIGURE 2 - graphs showing the results of a checkerboard assay in the Staphylococcus aureus clinical isolate SA 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. [0073] 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.

[0074] FIGURE 4 - graphs showing the results of a checkerboard assay in the methicillin resistant Staphylococcus aureus (MRSA) clinical isolate MRSA 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.

[0075] FIGURE 5 - graphs showing the results of a checkerboard assay in the methicillin resistant Staphylococcus aureus (MRSA) ATCC 33591 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.

[0076] 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.

[0077] 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.

[0078] 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. [0079] FIGURE 9 - 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 gentamicin. Data represents mean ± SD of at least 2-3 independent experiments.

[0080] 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.

[0081 ] 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.

[0082] 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.

[0083] FIGURE 13 - graphs showing susceptibility of Acinetobacter baumannii clinical isolate CI 1 towards antibiotic treatment alone (Chloramphenicol - top panels A and B; and Colistin - bottom panels C and D) or in combination with glycerolipid. Left panels (A and C) represent the MIC values obtained in planktonic bacteria, and the right panels (B and D) show corresponding biofilm MBICs.

[0084] 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, and the right panels (B and D) show corresponding biofilm MBICs. [0085] FIGURE 15 - graphs showing 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, and the right panels (B, D and F) show corresponding biofilm MBICs.

[0086] FIGURE 16 - graphs showing susceptibility of Enterococcus faecium clinical isolate CI 1 towards antibiotic treatment alone (Gentamicin - top panels A and B; and Meropenem - bottom panels C and D) or in combination with glycerolipid. Left panels (A and C) represent the MIC values obtained in planktonic bacteria, and the right panels (B and D) show corresponding biofilm MBICs.

[0087] FIGURE 17 - graphs showing susceptibility of Pseudomonas aeruginosa clinical isolate CI ML towards antibiotic treatment alone (Cefepime - 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, and the right panels (B and D) show corresponding biofilm MBICs.

[0088] 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, and (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.

[0089] 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.

[0090] 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.

[0091 ] 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. [0092] 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.

[0093] 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.

[0094] FIGURE 24 - graphs showing susceptibility of Staphylococcus aureus (MRSA) ATCC 33591 strain towards to antibiotic treatment alone or in combination with glycerolipid. (A) Gentamicin, (B) Erythromycin and (C) Tobramycin susceptibility was investigated in planktonic susceptibility assays. Data points represented as the mean +/- SD.

[0095] FIGURE 25 - graphs showing susceptibility of Enterococcus clinical isolates to topical antibiotic treatment alone or in combination with glycerolipid. (A) Enterococcus faecium clinical isolate CI 1 Gentamicin susceptibility, and (B) 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.

[0096] FIGURE 26 - graphs showing susceptibility of Staphylococcus aureus (MRSA) clinical isolates to topical antibiotic treatment alone or in combination with glycerolipid. (A) 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.

[0097] 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.

[0098] 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.

[0099] FIGURE 29 - graphs showing susceptibility of Pseudomonas aeruginosa clinical isolates to topical antibiotic treatment alone or in combination glycerolipid. 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.

[0100] 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). The combination of Gentamicin (2 ug/mL) and Capmul (2 mg/mL) showed the same effect (P<0.05) as a single treatment with 64 ug/mL gentamicin. Results are mean ±SD (n=4).

DETAILED DESCRIPTION OF THE INVENTION

[0101 ] As indicated above, the inventors have determined that the activity of an antimicrobial agent can be potentiated when combined with a glycerolipid. Accordingly, amongst other applications, 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.

[0102] Certain disclosed embodiments provide compositions, methods, products, and uses thereof that have one or more advantages. For example, 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 Enterococcus faecalis, including when present in a biofilm; to provide one or more advantages, or to provide a commercial alternative. Other advantages of some embodiments of the present disclosure are provided herein.

[0103] Accordingly, in one embodiment, the present invention provides a composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) an antimicrobial agent,

[0104] As used herein, 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. In some embodiments, the acyl group is unbranched and saturated. In some embodiments, 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.

[0105] Methods for making a glycerolipid for use in the present invention would be known in the art. For example, 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. Alternatively, a glycerolipid may be obtained from coconut oil, or palm oil, or palm kernel oil by fractionated distillation followed by esterification with glycerol. [0106] 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. For example, 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).

[0107] In some embodiments, 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.

[0108] In some embodiments, the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid. For example, 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, about 55% to 100% w/w, 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 100% 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 100% 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 100% w/w, about 70% to 95% w/w, about 70% to 90% w/w, about 70% to 85% w/w, about 70% to 80% w/w, about 70% to 75% w/w, about 75% to 100% w/w, about 75% to 95% w/w, about 75% to 90% w/w, about 75% to 85% w/w, about 75% to 80% w/w, about 80% to 100% w/w, about 80% to 95% w/w, about 80% to 90% w/w, about 80% to 85% w/w, about 85% to 100% w/w, about 85% to 95% w/w, about 85% to 90% w/w, about 90% to 100% w/w, about 90% to 95% w/w, or about 95% to 100% w/w, of the total glyceride content of the glycerolipid. [0109] In some embodiments, 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.

[0110] In some embodiments, 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.

[0111 ] In some embodiments, the diglyceride content of the glycerolipid is about 20% to about 50% w/w of the total glyceride content of the glycerolipid. For example, 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, of the total glyceride content of the glycerolipid.

[0112] In some embodiments, 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.

[0113] In some embodiments, the monoglyceride content of the glycerolipid is about 60% w/w, the diglyceride content of the glycerolipid is about 33% w/w, and the triglyceride content of the glycerolipid is about 5% w/w, of the total glyceride content of the glycerolipid.

[0114] In some embodiments, the monoglyceride content of the glycerolipid is about 59% w/w, the diglyceride content of the glycerolipid is about 34% w/w, and the triglyceride content of the glycerolipid is about 6% w/w, of the total glyceride content of the glycerolipid.

[0115] In some embodiments, the monoglyceride content of the glycerolipid is about 50% w/w, the diglyceride content of the glycerolipid is about 39% w/w, and the triglyceride content of the glycerolipid is about 8% w/w, of the total glyceride content of the glycerolipid.

[0116] As indicated above, the glycerolipid may be formed by linking glycerol to a C6 to C22 fatty acid acyl group. However, in some embodiments the glycerolipid may only comprise medium chain length fatty acids, i.e. fatty acids with aliphatic tails of 6 to 12 carbons. In this instance, the acyl group may be derived from, for example, caprylic acid (C8), capric acid (C10), and/or lauric acid (C12). In some embodiments, the glycerolipid only comprises caprylic acid and capric acid.

[0117] In some embodiments, 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. In some embodiments, the caprylic acid content of the glycerolipid is about 55% to about 99% w/w of the total fatty acid content of the glycerolipid. For example, 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/w, about 70% to 95% w/w, about 70% to 90% w/w, about 70% to 85% w/w, about 70% to 80% w/w, about 70% to 75% w/w, about 75% to 99% w/w, about 75% to 95% w/w, about 75% to 90% w/w, about 75% to 85% w/w, about 75% to 80% w/w, about 80% to 99% w/w, about 80% to 95% w/w, about 80% to 90% w/w, about 80% to 85% w/w, about 85% to 99% w/w, about 85% to 95% w/w, about 85% to 90% w/w, about 90% to 99% w/w, or about 90% to 95% w/w, of the total fatty acid content of the glycerolipid.

[0118] In some embodiments, 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. In some embodiments, the capric acid content of the glycerolipid is about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid. For example, 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 15% to 42% w/w, about 15% to 40% w/w, about 15% to 35% w/w, about 15% to 30% w/w, about 15% to 25% w/w, about 15% to 20% w/w, about 20% to 42% 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 42% w/w, about 25% to 40% w/w, about 25% to 35% w/w, about 25% to 30% w/w, about 30% to 42% w/w, about 30% to 40% w/w, about 30% to 35% w/w, about 35% to 42% w/w, about 35% to 40% w/w, or about 40% to 42% w/w, of the total fatty acid content of the glycerolipid.

[0119] In some embodiments, 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.

[0120] In some embodiments, 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.

[0121 ] In some embodiments, 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.

[0122] In some embodiments, the glycerolipid may be purchased from commercial sources such as ABITEC Corporation (Columbus, Ohio, USA) or Cremer Oleo GmbH & Co. KG (Hamburg, Germany). In this regard, in some embodiments the glycerolipid may be selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.

[0123] In some embodiments, 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:

(i) a glycerolipid; and

(ii) an antibiotic,

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. [0124] 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. 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.

[0125] Examples of 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. Examples of 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, dalfopristin and quinupristin), retapamulin, ethionamide, mupirocin, oxazolidinones (such as linezolid, posizolid, radezolid and torezolid) and telithromycin.

[0126] Examples of 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, ceftizoxime, ceftriaxone, cefepime, ceftaroline fosamil and ceftobiprole), monobactams (such as aztreonam), fosfomycin, polymyxin B, bacitracin, colistin, glycopeptides (such as teicoplanin, vancomycin, telavancin, dalbavancin and oritavancin), and beta-lactamase inhibitors (such as clavulanic acid, sulbactam, tazobactam, tebipenem, avibactam and relebactam).

[0127] Examples of 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.

[0128] Examples of RNA synthesis inhibitors include, but are not limited to, rifamycins such as rifampin and rifapentine.

[0129] Mechanosensitive channels of large conductance (MscL) consists of pore- forming membrane proteins that are responsible for translating physical forces applied to cell membranes into electrophysiological activities. MscL have a relativel large conductance, 3 nS, making them permeable to ions, water, and small proteins when opened. Examples of MscL can be found at http://www.tcdb. org/search/result.php?tc=1 .A.22.3. One specific example is Ramizol, which belongs to the styrylbenzene class of antibiotics.

[0130] Examples of 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.

[0131 ] 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.

[0132] In some embodiments, 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. For example, the antibiotic may be selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin. [0133] In some embodiments, the antimicrobial agent is an antiseptic. Accordingly, in a further aspect, the present invention provides a composition comprising:

(i) a glycerolipid; and

(ii) an antiseptic,

wherein 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.

[0134] Antiseptics for use in the present invention include alcohols, chlorhexidine, triclosan, hydrogen peroxide, iodine, octenidine dihydrochloride, polyhexanide, Balsam of Peru, and Dakin's solution. In one specific embodiment, chlorhexidine is used. In some embodiments, the composition is suitable for administration to a subject.

[0135] The inventors have surprisingly found that presence of a glycerolipid potentiates the activity of the antibiotic or antiseptic. As used herein, to "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. In other words, 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.

[0136] Methods for measuring the activity of the antibiotic or antiseptic would be well known in the art. For example, 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. For example, 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. [0137] Methods for determination of MICs, MBCs and MBICs would be well known in the art, some of which are described herein. Furthermore, MIC values for various antibiotics and bacteria can be obtained from the Antimicrobial Index at http://antibiotics.toku-e.com.

[0138] In some embodiments, 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. For example, 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.

[0139] The composition of the present invention is suitable for administration to a subject. This means that the composition can take a number of physical forms depending on the nature of the use of the composition and required mode of administration. In this regard, 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, β-tricalcium phosphate or a combination thereof. Other routes of administration are contemplated.

[0140] 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. In some embodiments, an administration vehicle (e.g., liquid, gel, paste, powder, cream, pill, tablet, capsule, injectable solution, aerosol, etc) would contain the composition and/or additional substance(s). In this regard, 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.

[0141 ] In some embodiments, 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. The term "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. Some examples of 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 as sodium lauryl sulfate and magnesium stearate, as well as colouring agents, releasing agents, coating agents, sweetening, flavouring and perfuming agents, preservatives and antioxidants can also be present.

[0142] The preparation of such pharmaceutical compositions is known in the art, for example as described in Remington's Pharmaceutical Sciences, 18th ed., 1990, Mack Publishing Co., Easton, Pa. and U.S. Pharmacopeia: National Formulary, 1984, Mack Publishing Company, Easton, Pa, which are incorporated herein by reference in their entirety.

[0143] In some embodiments, 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. [0144] 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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] 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.

[0149] The 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.

[0150] 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. A variety of 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.

[0151 ] As indicated above, in some embodiments the 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.

[0152] In some embodiments, the composition of the present invention may be formulated for parenteral administration. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal, and intracranial injection or infusion techniques.

[0153] 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. Examples of such 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. Among the acceptable vehicles and solvents that may be employed are water, saline, Ringer's solution, dextrose solution, isotonic sodium chloride solution, and Hanks' solution. In addition, sterile, fixed oils are conventionally employed as solvents or suspending mediums. For this purpose, 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.

[0154] 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.

[0155] In some embodiments, 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.

[0156] The composition of the present invention may also be formulated using controlled release technology. For example, the composition may be administered as a sustained- release pharmaceutical. To further increase the sustained release effect, 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. 20,000 to 400,000), 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).

[0157] Alternatively, 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. Methods for delivering agent(s) via scaffolds are known in the art. For example, a biomaterial scaffold including a scaffold produced from collagen, hydroxyapatite, β- 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.

[0158] 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. Such 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.

[0159] 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.

[0160] In some embodiments, 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 to 1 00 mg/g ; 1 mg/g to 10 mg/g ; 10 mg/g to 1 ,000 mg/g; 1 0 mg/g to 500 mg/g ; 1 0 mg/g to 250 mg/g ; 1 0 mg/g to 1 00 mg/g; 100 mg/g to 1 ,000 mg/g; 100 mg/g to 500 mg/g ; 1 00 mg/g to 250 mg/g ; 250 mg/g to 1 ,000 mg/g ; 250 mg/g to 500 mg/g ; and 500 mg/g to 1 ,000 mg/g. Other ranges are contemplated with the ultimate amount dictated by the glycerolipid used, and the antimicrobial agent which is combined with the glycerolipid.

[0161 ] In some embodiments, 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 μg/ml to 1 ,000 μg/ml, 1 μg/ml to 1 ,000 μg/ml, 10 μg/ml to 1 ,000 μg/ml, 100 μg/ml to 1 ,000 μg/ml, 500 μg/ml to 1 ,000 μg/ml, 0.1 μg/ml to 500 μg/ml, 1 μg/ml to 500 μg/ml, 1 0 μg/ml to 500 μg/ml, 1 00 μg/ml to 500 μg/ml, 0.1 μg/ml to 250 μg/ml, 1 μg/ml to 250 μg/ml, 10 μg/ml to 250 μg/ml, 1 00 μg/ml to 250 μg/ml, 0.1 μg/ml to 100 μg/ml, 1 μg/ml to 100 μg/ml, or 10 μg/ml to 100 μg/ml. Other ranges are contemplated with the ultimate amount dictated by the antimicrobial agent used, and the glycerolipid which is combined with the antimicrobial agent.

[0162] As indicated above, the inventors have determined that glycerolipids with the characteristics defined herein can potentiate the activity of antimicrobial agents. Accordingly, amongst other applications, the composition of the present invention may be used to treat or prevent an infection in a subject.

[0163] 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 one or more symptoms in the subject; (viii) a cure of a disease, condition or state in the subject. [0164] 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. In some embodiments, 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.

[0165] In some embodiments, 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.

[0166] In some embodiments, the microorganism is a bacterium and therefore infection is due to a bacterium. In some embodiments, the bacterium comprises a Gram positive bacterium, a Gram negative bacterium, a Gram test non-responsive bacteria, an aerobic bacterium, or an anaerobic bacterium.

[0167] 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, Butyrivibrio, Calymmatobacterium, Campylobacter, Capnocytophaga, Cardiobacterium, Catonella, Cedecea, Cellulomonas, Centipeda, Chlamydia, Chlamydophila, Chromobacterium, Chyseobacterium, Chryseomonas, Citrobacter, Clostridium, Collinsella, Comamonas, Corynebacterium, Coxiella, Cryptobacterium, Delftia, Dermabacter, Dermatophilus, Desulfomonas, Desulfovibrio, Dialister, Dichelobacter, Dolosicoccus, Dolosigranulum, Edwardsiella, Eggerthella, Ehrlichia, Eikenella, Empedobacter, Enterobacter, Enterococcus, Erwinia, Erysipelothrix, Escherichia, Eubacterium, Ewingella, Exiguobacterium, Facklamia, Filifactor, Flavimonas, Flavobacterium, Francisella, Fusobacterium, Gardnerella, Globicatella, Gemella, Gordona, Haemophilus, Hafnia, Helicobacter, Helococcus, Holdemania, Ignavigranum, Johnsonella, Kingella, Klebsiella, Kocuria, Koserella, Kurthia, Kytococcus, Lactobacillus, Lactococcus, Lautropia, Leclercia, Legionella, Leminorella, Leptospira, Leptotrichia, Leuconostoc, Listeria, Listonella, Megasphaera, Methylobacterium, Microbacterium, Micrococcus, Mitsuokella, Mobiluncus, Moellerella, Moraxella, Morganella, Mycobacterium, Mycoplasma, Myroides, Neisseria, Nocardia, Nocardiopsis, Ochrobactrum, Oeskovia, Oligella, Orientia, Paenibacillus, Pantoea, Parachlamydia, Pasteurella, Pediococcus, Peptococcus, Peptostreptococcus, Photobacterium, Photorhabdus, Plesiomonas, Porphyrimonas, Prevotella, Propionibacterium, Proteus, Providencia, Pseudomonas, Pseudonocardia, Pseudoramibacter, Psychrobacter, Rahnella, Ralstonia, Rhodococcus, Rickettsia Rochalimaea Roseomonas, Rothia, Ruminococcus, Salmonella, Selenomonas, Serpulina, Serratia, Shewenella, Shigella, Simkania, Slackia, Sphingobacterium, Sphingomonas, Spirillum, Staphylococcus, Stenotrophomonas, Stomatococcus, Streptobacillus, Streptococcus, Streptomyces, Succinivibrio, Sutterella, Suttonella, Tatumella, Tissierella, Trabulsiella, Treponema, Tropheryma, Tsakamurella, Turicella, Ureaplasma, Vagococcus, Veillonella, Vibrio, Weeksella, Wolinella, Xanthomonas, Xenorhabdus, Yersinia, and Yokenella; Gram-positive bacteria such as, M. 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, E. hirae, Burkholderia cepacia, Burkholderia pseudomallei, Francisella tularensis, Bacteroides fragilis, Fusobascterium nucleatum, and Cowdria ruminantium. Other types of bacteria are contemplated. [0168] In some embodiments, the microorganism comprises a bacterium of the genus Staphylococcus, or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises Staphylococcus aureus or Staphylococcus epidermidis or a small colony variant or antimicrobial resistant variant thereof. In some embodiments, the microorganism comprises methicillin-resistant Staphylococcus aureus (MRSA) and therefore the bacterial infection is due to MRSA.

[0169] In some embodiments, 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.

[0170] In some embodiments, 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.

[0171 ] In some embodiments, 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.

[0172] In some embodiments, 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.

[0173] In some embodiments, 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.

[0174] As well as the continued resistance to antibiotic effectiveness, a further complication is that some bacterial infections are difficult to treat given that the bacteria are resident in a biofilm. A 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.

[0175] The 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. Indeed, 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.

[0176] Accordingly, in some embodiments the bacterial infection forms part of a biofilm. Examples of 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).

[0177] In some embodiments, the bacterial infection comprises an infected wound. Examples of 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. In some embodiments, the bacterial infection comprises a post-surgery infected wound, for example an infected wound following abdominal surgery or sinus surgery.

[0178] Methods for assessing bacterial infection are known in the art. For example, bacterial infection in a wound would delay healing of the wound. As such 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. An exemplary scratch wound assay can be found in Chen Y, 2012, Bio-protocol 2(5): e100. Other commonly used wound assays can be found in Kopecki W et al., 2017, Wound Practice and Research, 25(1 ): 6-13. A further specific wound assay is described in Example 4 below.

[0179] In some embodiments, the microorganism is a fungus and therefore the infection is due to a fungus. In this regard, the antimicrobial agent is an antifungal.

[0180] Accordingly, in a further aspect the present invention provides a composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) an antifungal,

wherein 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.

[0181 ] The level of potentiation, and methods for measuring the potentiation, of the antifungal are as described above with respect to an antibiotic or antiseptic.

[0182] Examples of fungal infections are described herein and 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, Trichtophyton, Trichurus, and Ulocladium. Other types of fungi are contemplated.

[0183] In some embodiments, the infection may be due to a fungal skin or mucosal infection. In some embodiments, the fungal infection is due to Candida albicans.

[0184] In some embodiments, 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.

[0185] An "antifungal" as used herein means a biocidal compound that can inhibit the growth of, or kill, fungi or fungal spores. In some embodiments, the antifungal may be selected from one or more of a polyene, an azole, an allylamine, and an echinocandin.

[0186] 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.

[0187] In some embodiments, the polyene antifungal is selected from one or more of amphotericin B, candicidin, filipin, hamycin, natamycin, nystatin and rimocidin.

[0188] An azole antifungal can inhibit the enzyme lanosterol 14 α-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.

[0189] In some embodiments, the azole antifungal is selected from an imidazole, a triazole, and/or a thiazoie. For example, 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. [0190] 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.

[0191 ] An echinocandin inhibits the synthesis of glucan in the cell wall via the enzyme 1 ,3- Beta-glucan synthase. In some embodiments, the echinocandin antifungal may be selected from anidulafungin, caspofungin and micafungin.

[0192] 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.

[0193] In some embodiments, the antifungal is selected from an azole and/or amphotericin B.

[0194] As used herein, the term "subject" should be taken to encompass any subject which would benefit from administration of the composition of the present invention. In some embodiments, 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.

[0195] In some embodiments, the composition of the present invention, or a formulation thereof, does not comprise a cationic surfactant.

[0196] In some embodiments, the composition of the present invention, or a formulation thereof, has a pH in the physiological range of 5.5 (skin) to 7.35 (blood).

[0197] In recognition that the activity of an antimicrobial agent can be potentiated by the presence of a glycerolipid, 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. [0198] 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.

[0199] 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.

[0200] In some embodiments of the aforementioned methods, 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 μg/ml to 1 ,000 μg/ml, 1 μg/ml to 1 ,000 μg/ml, 10 μg/ml to 1 ,000 μg/ml, 100 μg/ml to 1 ,000 μg/ml, 500 μg/ml to 1 ,000 μg/ml, 0.1 μg/ml to 500 μg/ml, 1 μg/ml to 500 μg/ml, 10 μg/ml to 500 μg/ml, 100 μg/ml to 500 μg/ml, 0.1 μg/ml to 250 μg/ml, 1 μg/ml to 250 μg/ml, 1 0 μg/ml to 250 μg/ml, 100 μg/ml to 250 μg/ml, 0.1 μg/ml to 1 00 μg/ml, 1 μg/ml to 1 00 μg/ml, or 10 μg/ml to 100 μg/ml. Other ranges are contemplated with the ultimate amount dictated by the antimicrobial agent used, and the glycerolipid which is combined with the antimicrobial agent.

[0201 ] In some embodiments, 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 μg/ml to 1 28 μg/ml. [0202] In some embodiments, 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 μg/ml to 128 μg/ml.

[0203] In some embodiments, 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 μg/ml to 1024 μg/ml.

[0204] In some embodiments, 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 μg/ml to 128 μg/ml.

[0205] In some embodiments, 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 μg/ml to 64 μg/ml.

[0206] In some embodiments, 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 μg/ml to 16 μg/ml.

[0207] In some embodiments, 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 μg/ml to 256 μg/ml.

[0208] In some embodiments, 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 μg/ml to 128 μg/ml. [0209] In some embodiments, 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 μg/ml to 2,000 μg/ml.

[0210] In some embodiments, 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 μg/ml to 256 μg/ml.

[0211 ] In some embodiments, 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 μg/ml to 256 μg/ml.

[0212] In some embodiments, 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 μg/ml to 126 μg/ml.

[0213] In some embodiments, 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 μg/ml to 2.0 μg/ml.

[0214] In some embodiments of the aforementioned methods, 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 μg/kg to 1000 mg/kg; 1 μg/kg to 100 mg/kg; 1 μg/kg to 10 mg/kg; 1 μg/kg to 1 mg/kg; 1 μg/kg to 100 μg/kg; 1 μg/kg to 10 μg/kg; 10 μg/kg to 1000 mg/kg; 10 μg/kg to 100 mg/kg; 10 μg/kg to 10 mg/kg; 10 μg/kg to 1 mg/kg; 10 μg/kg to 100 μg/kg; 100 μg/kg to 1000 mg/kg; 100 μg/kg to 100 mg/kg; 100 μg/kg to 10 mg/kg; 100 μg/kg to 1 mg/kg; 1 mg/kg to 1000 mg/kg; 1 mg/kg to 100 mg/kg; 1 mg/kg to 10 mg/kg; 10 mg/kg to 1000 mg/kg; 10 mg/kg to 100 mg/kg; and 100 mg/kg to 1000 mg/kg body weight of the subject. The dose and frequency of administration may be determined by one of skill in the art. [0215] In some embodiments of the aforementioned methods, 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/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 to 100 mg/g; 1 mg/g to 10 mg/g; 10 mg/g to 1 ,000 mg/g; 10 mg/g to 500 mg/g; 10 mg/g to 250 mg/g; 10 mg/g to 100 mg/g; 100 mg/g to 1 ,000 mg/g; 100 mg/g to 500 mg/g; 100 mg/g to 250 mg/g; 250 mg/g to 1 ,000 mg/g; 250 mg/g to 500 mg/g; and 500 mg/g to 1 ,000 mg/g. Other ranges are contemplated with the ultimate amount dictated by the glycerolipid used, and the antimicrobial agent which is combined with the glycerolipid.

[0216] In some embodiments, 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.

[0217] In some embodiments of the aforementioned methods, 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 μg kg to 100 mg/kg; 0.01 μg kg to 10 mg/kg; 0.01 μg/kg to 1 mg/kg; 0.01 μg kg to 100 μg/kg; 0.01 μg kg to 10 μg/kg; 0.01 μg kg to 1 μg/kg; 0.1 μg/kg to 100 mg/kg; 0.1 μg/kg to 10 mg/kg; 0.1 μg/kg to 1 mg/kg; 0.1 μg/kg to 100 μg/kg; 0.1 μg/kg to 10 μg/kg; 0.1 μg/kg to 1 μg/kg; 1 μg/kg to 100 mg/kg; 1 μg/kg to 10 mg/kg; 1 μg/kg to 1 mg/kg; 1 μg/kg to 100 μg/kg; 1 μg/kg to 10 μg/kg; 10 μg kg to 100 mg/kg; 10 μg kg to 10 mg/kg; 10 μg kg to 1 mg/kg; 10 μg kg to 100 μg/kg; 100 μg kg to 100 mg/kg; 100 μg kg to 10 mg/kg; 100 μg kg to 1 mg/kg; 1 mg/kg to 10 mg/kg; and 10 mg/kg to 100 mg/kg body weight of the subject. The dose and frequency of administration may be determined by one of skill in the art.

[0218] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Staphylococcus aureus. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, vancomycin, and chloramphenicol. [0219] Accordingly, in a further aspect 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.

[0220] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by MRSA. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefepime, gentamicin, erythromycin, tobramycin, and ciprofloxacin.

[0221 ] Accordingly, in a further aspect 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.

[0222] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Pseudomonas aeruginosa. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, cefepime, and tobramycin.

[0223] Accordingly, in a further aspect 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.

[0224] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Escherichia coli. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and tobramycin.

[0225] Accordingly, in a further aspect 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.

[0226] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Klebsiella pneumoniae. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of cefazolin, gentamicin, and colistin.

[0227] Accordingly, in a further aspect 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.

[0228] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Acinetobacter baumannii. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of colistin, chloramphenicol, gentamicin, amikacin, and ciprofloxacin.

[0229] Accordingly, in a further aspect 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.

[0230] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Enterococcus faecium. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is selected from one or more of gentamicin, meropenem, erythromycin, and bacitracin.

[0231 ] Accordingly, in a further aspect 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. [0232] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Staphylococcus epidermidis. In some embodiments, the glycerolipid is Capmul MCM and the antiseptic is chlorhexidine.

[0233] Accordingly, in a further aspect 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.

[0234] In some embodiments of the aforementioned methods, the infection is a bacterial infection caused by Enterococcus faecalis. In some embodiments, the glycerolipid is Capmul MCM and the antibiotic is tobramycin.

[0235] Accordingly, in a further aspect 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.

[0236] In some embodiments, 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.

[0237] Accordingly, in a further aspect 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.

[0238] In some embodiments, the method comprises topical administration of the composition. [0239] In a further aspect 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.

[0240] In a further aspect 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. Examples of wounds are as described herein, such as a cut or abrasion, or a wound arising during surgery.

[0241 ] In some embodiments, the method comprises topical administration of the composition.

[0242] In a further aspect 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.

[0243] Exemplary bacterial species which may cause infection of a wound are described above.

[0244] In a further aspect, 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. [0245] In a further aspect, 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.

[0246] Methods for assessing the viability of microorganisms, including bacteria and fungi, are known in the art. Exemplary microorganisms, including bacteria and fungi, are described above.

[0247] In some embodiments, the microorganism is present in vitro.

[0248] In some embodiments, 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. For example, 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.

[0249] In some embodiments, 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. Examples of 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. In one embodiment, the glycerolipid may be combined with an antiseptic such as chlorhexidine for such applications.

[0250] Furthermore, 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. In some embodiments, the glycerolipid may be combined with an antiseptic such as chlorhexidine for such applications. Accordingly, 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. As used herein, 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.

[0251 ] Accordingly, in a further aspect 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.

[0252] In some embodiments, the microorganism is present in a biological setting. In some embodiments, the microorganism is present in vitro in a biological setting.

[0253] In some embodiments, the microorganism is present in a biological system. The term "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. In certain embodiments, 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.

[0254] In some embodiments, the microorganism is present in vivo. In some embodiments, a subject is infected with the microorganism.

[0255] In some embodiments, 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.

[0256] In some embodiments, 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. In some embodiments, 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 10⁴ fold or more, by 10⁵ fold or more, or by 10⁶ fold or more. Other levels of reduction of viability are contemplated.

[0257] In some embodiments, 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.

[0258] The term "exposing", and related terms such as "expose" and "exposure", as used herein refers to directly and/or indirectly contacting and/or treating a microorganism with a glycerolipid and an antimicrobial agent.

[0259] Methods for exposing a microorganism to compositions are known in the art. For example, 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.

[0260] For a microorganism in vitro, 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.

[0261 ] For a microorganism ex vivo, 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.

[0262] For a microorganism in vivo, 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.

[0263] The concentration or amount of glycerolipid and antimicrobial agent that the microorganism is exposed to has been described above. [0264] In one aspect, the present invention provides a kit. The kit may comprise the composition of the invention, the individual components of the composition, and/or instructions for performing a method described herein.

[0265] In some embodiments, the kit may be used for the treatment or prevention of an infection in a subject. In some embodiments, 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.

[0266] In some embodiments, 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. In some embodiments, the glycerolipid and antimicrobial agent are provided already combined as a single composition. In this instance, the kit may again include instructions for administering the composition in defined amounts to treat or prevent the infection. In some embodiments, the kit may include instructions for suitable operational parameters in the form of a label or separate insert.

[0267] It is to be noted that where a range of values is expressed, it will be clearly understood that this range encompasses the upper and lower limits of the range, and all values in between these limits.

[0268] The term "about" as used in the specification means approximately or nearly and in the context of a numerical value or range set forth herein is meant to encompass variations of +/- 10% or less, +/- 5% or less, +/- 1 % or less, or +/- 0.1 % or less of and from the numerical value or range recited or claimed.

[0269] As used herein, the singular forms "a," "an," and "the" may refer to plural articles unless specifically stated otherwise.

[0270] Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers. [0271 ] All methods described herein can be performed in any suitable order unless indicated otherwise herein or clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the example embodiments and does not pose a limitation on the scope of the claimed invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential.

[0272] It will be apparent to the person skilled in the art that while the invention has been described in some detail for the purposes of clarity and understanding, various modifications and alterations to the embodiments and methods described herein may be made without departing from the scope of the inventive concept disclosed in this specification.

[0273] Furthermore, the description provided herein is in relation to several embodiments which may share common characteristics and features. It is to be understood that one or more features of one embodiment may be combinable with one or more features of the other embodiments. In addition, a single feature or combination of features of the embodiments may constitute additional embodiments.

[0274] The subject headings used herein are included only for the ease of reference of the reader and should not be used to limit the subject matter found throughout the disclosure or the claims. The subject headings should not be used in construing the scope of the claims or the claim limitations.

[0275] The invention is further illustrated in the following examples. The examples are for the purpose of describing particular embodiments only and are not intended to be limiting with respect to the above description. It will be appreciated by those skilled in the art that the disclosure may be embodied in many other forms.

EXAMPLE 1

Glvcerolipids Potentiate the Activity of Antibiotics against Resistant Bacteria

[0276] 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.

MATERIALS AND METHODS

[0277] 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) and 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).

[0278] Six strains from the ESKAPE group of 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, Adelaide, South Australia 5000, Australia).

Bacterial Culture

[0279] Bacteria were propagated from frozen stock (-80°C) and incubated overnight (18- 24 h) at 37°C on Tryptic Soy Agar (TSA) unless stated otherwise.

Minimum Inhibitory Concentration

[0280] 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 (OD₆₀₀) of 0.10 ± 0.02, corresponding to a cell density of 1 -2 x 10⁸ colony forming units (CFU)/mL . A 1 in 100 dilution of the bacterial suspension in suitable medium (Mueller Hinton unless noted differently) 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 .

[0281 ] Briefly, 100 μL of sterile broth was added to the wells of column 12 (negative control) and 50 μL of sterile broth was added to the wells of column 1 1 (positive control). Next, 50 μL of the diluted bacterial suspension was added to the wells of column 1 1 , resulting in a final cell density of approximately 5 x 10⁵ CFU/mL and volume of 100 μL_. Inoculum (100 μL ) was then added to the wells of columns 1 to 10. Thereafter, 100 μL_ of treatment was added to the wells of column 1 and mixed thoroughly with the bacterial suspension taking care not to contaminate the surrounding wells. This resulted in a 1 :1 dilution of the treatment in column 1 and a volume of 200 μL_. Serial dilution was carried out by transferring 100 μL_ of the first treatment/bacteria mixture to the next column (i.e. column 2) using a multi-channel pipette. The content was mixed thoroughly. Column 1 then contained 100 μL_ of the bacterial/treatment mixture, and column 2 contained 200 μL_. This procedure was repeated until all 10 columns were diluted and the 100 μL of the treatment/bacteria mix in column 10 were discarded. The plate was then wrapped in aluminium foil to prevent evaporation and protect the antibiotics from light, and incubated statically for 16-20 h (typically 18 hours) at 37°C. The lowest concentration of the antibiotic (or lipid) that prevented the visible growth of the organism was defined as the MIC.

Quality Control Inoculum

[0282] Samples (10 μL_) of the final positive control (wells in column 1 1 ) were verified for cell density (target 5 x 10⁵ 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.

Checkerboard Assay in Planktonic Bacteria

[0283] To evaluate the interaction of antibiotic and glycerolipid and determine potentially synergistic antimicrobial effects of their combination, a checkerboard assay was carried out. First a dilution series of both compounds was prepared in the desired concentration range. Compound 1 was added in horizontally decreasing concentrations while compound 2 was added vertically at decreasing concentrations. The MIC was defined as the lowest concentration of antibiotic that prevented the visible growth of the organism used in combinations with glycerolipids. Table 1 summarises the antibiotics that were tested alone and in combination with glycerolipids.

[0284] 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.

Biofilm Growth

[0285] 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 10⁸ CFU/mL, diluted 1/15 with broth and then 100 μΐ 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 plates were incubated for 24 hours at 37°C on a gyratory shaker (Ratek Instruments, Boronia, VIC, Australia) at 70 rpm. Following the removal of the media the wells were carefully washed twice with sterile saline to remove adhering planktonic bacteria. Checkerboard Assay in Biofilms

[0286] The procedure was similar to the checkerboard assay in planktonic bacteria, however a higher initial concentration of antibiotic was used. Biofilms were grown as described above before exposing them for 24 hours to either glycerolipids or antibiotics alone or to combinations thereof using the checkerboard assay. To determine cell viability in biofilms the resazurin/resorufin (AlamarBlue) cell viability assay (Life Technologies, Mulgrave, VIC, Australia) was used according to the manufacturer's protocol.

[0287] Briefly, a 1 in 10 dilution of AlamarBlue stock solution was prepared in medium and 100 μL_ of this solution was added to the washed biofilms. The plates were incubated at 37°C and the fluorescence (excitation λ = 505 nm, emission λ = 600 nm) was measured every 30 minutes in an EnSpire multiplate reader (Perkin Elmer, Waltham, MA, USA) until maximum fluorescence was reached in maximum growth controls. 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).

% BK = (Fl controls - Fl exposed)/ Fl controls ^χ 100% Equation 1

[0288] Complete biofilm killing was defined as 100 ± 5% BK. The minimum biofilm inhibitory concentration (MBIC) was defined as the lowest concentration at which no growth of bacteria was detected (i.e. lowest concentration to achieve 100% BK).

RESULTS AND DISCUSSION

Antimicrobial activity of antibiotics and glycerolipids in planktonic and biofilm associated bacteria - effect of single compounds

[0289] The MICs and MBICs of the tested antibiotics and glycerolipids are summarised in Table 1 . In all cases, and consistent with previous reports, the MBIC was increased compared to the MIC. For example, while 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. Moreover, in biofilms 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. β-lactamase) resulting in reduced exposure to antimicrobials. [0290] While 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).

[0291 ] Following MIC and MBIC studies checkerboard assays were carried out in planktonic bacteria and in biofilms to investigate the antimicrobial effects of antibiotic/lipid combinations. Pathogens for which high MIC or MBIC were determined in the initial screening (indicating resistance against the respective antibiotic) were selected for further studies using checkerboard assays (bold numbers in Table 1 ).

Checkerboard Assays - Screening of Monoglycerides/Diglycerides

[0292] The USP- NF and Ph. Eur. monographs for mono/diglycerides (Glyceryl Monocaprylocaprate Type I and Glycerol Monocaprylocaprate Type I, respectively) allow relatively broad ratios of monoacylglycerols (45%-100%), diacyclglycerols (20% -50%) and triacylglycerols (≤10%) resulting in various commercially available mono/diglyceride products. Moreover, the commercial mono/diglycerides differ in the relative composition of the fatty acids that have been used in the esterification of glycerol.

[0293] As an example, 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).

[0294] As another example, 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).

[0295] As a further example, 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).

[0296] To investigate the effect of mono/diglycerides and fatty acid composition on the antimicrobial effects in combination with antibiotics, three different mono/diglycerides were tested (i.e. Capmul MCM, Imwitor 742, and Imwitor 988) in combination with gentamicin in a clinical isolate of S. aureus.

[0297] All glycerolipids tested enhanced the antimicrobial effect of gentamicin to a similar extent with comparable MICs (range: 0.25-1 mg/L depending on the glycerolipid amount) observed in checkerboard assays (see Figures 2 and 3) indicating a class-effect of mono/diglycerides. Capmul MCM was selected as the glycerolipid for the subsequent checkerboard assays in other organisms and antibiotics (as detailed below).

Antimicrobial Activity in Planktonic and Biofilm Associated Bacteria

[0298] As is evident from Figures 2 to 1 1 , the combination of mono/diglycerides with antibiotics substantially lowered the MIC and/or the MBIC of the tested ESKAPE pathogens, i.e. substantially less antibiotic was required in combination with the glycerolipids to inhibit bacterial growth compared to antibiotic alone.

[0299] The susceptibility towards antibiotics increased 8 to 250-fold, most notably in two clinical isolates (S. aureus and MRSA). This is an important finding as clinical isolates are often multi-resistant and extremely challenging to treat. It is particularly important to note that the gentamicin resistant strain (MRSA ATCC 33591 , clinical breakpoint of > 1 mg/L according to EUKAST 2017 breakpoint http://www.eucast.org/clinical_breakpoints/) became sensitive when the antibiotic (≤ 1 mg/L gentamicin) was combined with 0.0635 mg/g mono/diglyceride (see Figure 5). [0300] The increased susceptibility was independent of the phenotype of these Gram- positive bacteria as the elevated antimicrobial activity was observed both in the planktonic and biofilm mode of growth. Interestingly, the combination of antibiotic and glycerolipid demonstrated no enhanced antimicrobial effects compared to antibiotic alone against Gram-negative planktonic E. coli, K. pneumoniae (quality control strains) and P. aeruginosa (clinical isolate) (see Figures 6 to 1 1 ). However, when grown as biofilms these strains also demonstrated enhanced sensitivity to antibiotic/lipid combinations.

[0301 ] It is worth noting that enhanced antimicrobial effects in planktonic bacteria and biofilms were observed for different antibiotic classes, i.e. for cephalosporins (cefazolin/cefepime) and the aminoglycoside gentamicin. This suggests that a specific mechanism of action of the antibiotic (interruption of cell-membrane synthesis or protein synthesis, respectively) was not critical for enhancing its antimicrobial effect. While not wishing to be bound by theory, 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.

Interaction of Antibiotic/ Glycerolipid Combinations

[0302] To quantify the interaction between antibiotics and glycerolipids, the fractional inhibitory concentration (FIC) index was calculated which can be used to describe the type of interaction between antibiotics and other compounds (see de la Fuente-Nunez C et al., 2015, Chem. Biol., 22(2): 196-205). As evidenced in Table 2, in all cases additive or synergistic effects of antibiotic/glycerolipid combinations were identified. Synergistic antimicrobial effects were found against all biofilms, except E.coli for which additive effects were shown. In contrast, synergy was observed both against the planktonic and biofilm forms of S. aureus.

[0303] To the best of our knowledge this is the first study to report amplified (either additive or synergistic) antimicrobial effects of mono/diglyceride-antibiotic combinations against planktonic bacteria and biofilms. Despite their clinical importance, biofilms are not routinely investigated in antimicrobial efficacy studies. The findings presented here are highly significant as bacteria adopting the sessile biofilm state of growth are extremely tolerant to antibiotics (Stewart PS and J. William Costerton, 2001 , The Lancet, 358(9276): 135-138). Several factors contribute to this phenomenon, including: i) the existence of nutrient and oxygen gradients reducing the physiological activity within the cells of the biofilm which in turn compromises the activity of antibiotics that rely on metabolic active cells; and ii) chemical or physical inactivation of antibiotics by the biofilm matrix (Bjarnsholt T, 2013, Acta Pathologica et Microbiologica Scandinavica, 121 : 1 -58; and Fux CA et al., 2005, Trends in Microbiology, 13(1 ): 34-40). Moreover, the close proximity of bacteria within the biofilm matrix promotes the development of resistance by the rapid exchange of resistance genes. Together these adaptive mechanisms facilitate the survival of bacteria even in adverse conditions. Clinically this corresponds to prolonged antibiotic therapy, infection relapse, repeated surgical intervention, high health care costs as well as high mortality in the majority of device- and tissue-related infections (Bjarnsholt T, 2013, supra). The increased susceptibility of planktonic bacteria or biofilms against antibiotic/glycerolipid combinations demonstrated in this study represents a promising alternative treatment strategy for biofilm-associated infections and a possible exit route out of the current antibiotic resistance dilemma.

[0304] By combining approved antibiotics with pharmaceutical grade glycerolipids this study reports on a unique approach to potentiate the antimicrobial effects of clinically relevant antibiotics. Demonstrated herein is dramatically enhanced antibiotic activity of these combinations compared to individual treatments against planktonic and biofilm- associated S. aureus (including MRSA), P. aeruginosa, E. coli and K pneumoniae.

EXAMPLE 2

Testing of Glycerolipid/Antibiotic Combinations

[0305] 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 .

Screening of ESKAPE pathogens with systemic antibiotics

[0306] 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.

[0307] The 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, Adelaide, South Australia 5000, Australia). [0308] The antibiotics tested included chloramphenicol, gentamicin, vancomycin, colistin, tobramycin, cefazolin, meropenem, and cefepime. The antibiotics were obtained from Sigma-Aldrich (Castle Hill, NSW, Australia).

[0309] Assays were carried out in 96 well plates. MICs were assessed both visually and by plate reading (OD₆₀₀), 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).

[0310] The susceptibilities of the ESKAPE pathogens towards frequently used systemic antibiotics were evaluated with and without the presence of the mono-diglyceride Capmul MCM. First, the MICs and MBICs were established without added Capmul to guide the concentration selection for subsequent combination treatments using a checkerboard design. Figures 12 to 17 summarise the findings for each pathogen 1 ) in planktonic (free floating) bacteria (left columns); and 2) as (surface attached) biofilm (right columns). Biofilms were included as they are notoriously less sensitive and far more difficult to treat compared to planktonic cells.

[0311 ] Synergistic effects were observed for combination treatments. Importantly, this was observed across different classes of antibiotics (e.g. aminoglycosides, beta- lactam/cephalorosporines, macrolides, etc). Moreover, there was no clear trend observed against Gram positive or Gram negative bacteria. Interestingly, some strains (e.g. Pseudomonas, Escherichia) showed enhanced susceptibility in their biofilm mode of growth while not being affected in their planktonic state. Given the difficulties in biofilm- associated infections this is a very positive outcome for therapeutic intervention.

[0312] Consistent with the results seen in Example 1 , the presence of a glycerolipid significantly increased the sensitivity of all tested systemic antibiotics, independent from their mode of action and across ESKAPE pathogens. The most notable synergistic interactions were observed between Capmul and gentamicin (see Figures 12C and 12D; Figure 15F; Figures 16A and 16B; and Figure 17D), Capmul and vancomycin (see Figure 12F), Capmul and chloramphenicol (see Figures 13A and 13B), Capmul and colistin (see Figures 13C and 13D; and Figures 15C and 15D), Capmul and tobramycin (see Figure 14B), Capmul and cefazolin (see Figure 15B), and Capmul and cefepime (see Figure 17B).

Screening of ESKAPE pathogens with topical antimicrobial agents

[0313] 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, Adelaide, South Australia 5000, Australia). First, the strains were extensively screened against an array of topical antibiotics via minimum inhibition concentration (MIC) assays. 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.

[0314] 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).

[0315] A total of 38 bacterial strains were subjected to planktonic (free-floating) MIC assays against the topical antibiotics, and antiseptic agent as indicated above. Following European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, antimicrobial agent resistance was determined based on MIC results and the EUCAST cut-off values for the respective antimicrobial agent and bacterial strain. These cut-off values are determined by the various antimicrobial committees that comprise EUCAST and are based on collated clinical data. Cut-off values refer to the concentration at which the specific antimicrobial agent is likely to be effective at treating a respective bacterial infection in a given patient. [0316] Of the entire 38 strains tested, those identified as resistant organisms were then subjected to further investigation whereby topical antimicrobial agents were combined with the mono-diglyceride Capmul MCM to determine the potential of enhancing topical antimicrobial agent efficacy.

[0317] Combination studies were performed on both planktonic (free-floating) bacteria and biofilms (surface-attached). Bacteria produce biofilms as part of their strategy to evade the effects of antimicrobials, hence are notoriously difficult to treat. The results are represented in Table 3 and shown in Figures 18 to 24 which highlight findings from planktonic/ biofilm susceptibility studies for ESKAPE organisms obtained from ATCC, and Figures 25 to 29 which highlight findings from selected ESKAPE clinical isolates obtained from SA Pathology.

[0318] Consistent with the results seen above as well as those in Example 1 , the presence of a glycerolipid significantly increased the sensitivity of topical antimicrobial agent, independent from their mode of action and across ESKAPE pathogens.

EXAMPLE 3

Artificial Dermis Testing

[0319] Advanced biofilm assays using an artificial dermis (Richter et al. 2017, Frontiers Cellular Infection Microbiology, 7 (Article 280): 1 to 10) were carried out to identify a concentration of gentamicin and Capmul MCM that would perform synergistically under more stringent conditions compared to a simple 96-well plate assay. Since collagen (a protein component of the dermis model) is a nutrient source for bacteria even a modest reduction of bacteria can be considered beneficial.

[0320] A range of antibiotic (gentamicin)/Capmul concentrations and combinations were tested. It was evident that the effective concentration (0.5 ug/MI and 1 ug/MI) identified in the simple microwell plates were not effective in the artificial dermis.

[0321 ] As shown in Figure 30, the bacteria count following extraction from the dermis after 24 hour treatment indicated a colony count (CFU) as high as 1 X10⁹ (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 X10⁸. 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.

EXAMPLE 4

Animal Wound Assay

[0322] 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.

[0323] 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. Following the completion of wounding, a piece of dry sterile gauze is placed on each wound to absorb excess blood. Once excessive bleeding has ceased, 50 μL_ of a bacterial suspension to be tested (5 x 10⁷ 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.

[0324] Disease progression is monitored daily using a whole animal live imaging system I VIS (Lumina S5, Perkin Elmer) over 10 consecutive days. Once the infection is fully established (day 6) treatments with the antibiotic/glycerolipid or antiseptic/glycerolipid combinations are applied daily. Measurable study outcomes can include: (i) the reduction in the bacterial load following combination treatment vs individual compound treatment vs controls; and (ii) bioluminescence data correlating with bacterial count at study end (day 10) following wound excision and extraction of bacteria. EXAMPLE 5

Animal Models of Disease Phenotypes

[0325] A number of animal models of various disease phenotypes may be used to assess the efficacy of compositions of the present invention (comprising antimicrobial agent/glycerolipid combinations) in treating infection at various sites of the body. Exemplary models are provided below.

[0326] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the eyes (such as conjunctivitis or keratitis) 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.

[0327] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the ears (such as outer and inner ear infection - otitis externa and otitis media), which are often an issue in companion dogs or humans, 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.

[0328] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the nose or sinuses (such as microbial sinusitis and rhinosinusitis) 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. [0329] 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.

[0330] 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.

[0331 ] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the bones (such as osteomyelitis) 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.

[0332] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the bladder (such as bacterial cystitis, and urinary tract infections) 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.

[0333] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the vagina (such as bacterial vaginosis, or yeast infections such as Candidiasis) 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.

[0334] Assessment of antimicrobial agent/glycerolipid compositions of the present invention for treating infection of the large intestine (such as Clostridium difficile infection) 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.

[0335] Assessment of antimicrobial agent/glycerolipid 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.

EXAMPLE 6

Treatment of Subjects

[0336] 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.

Claims

1 . A composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) an antimicrobial agent,

2. The composition of claim 1 , wherein the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid.

3. The composition of claim 1 or claim 2, wherein the monoglyceride content of the glycerolipid is about 45% to about 75% w/w of the total glyceride content of the glycerolipid.

4. The composition of any one of claims 1 to 3, wherein the monoglyceride content of the glycerolipid is about 50% to about 60% w/w of the total glyceride content of the glycerolipid.

5. The composition of any one of claims 1 to 4, wherein the diglyceride content of the glycerolipid is about 20% to about 50% w/w of the total glyceride content of the glycerolipid.

6. The composition of any one of claims 1 to 5, wherein the diglyceride content of the glycerolipid is about 30% to about 40% w/w of the total glyceride content of the glycerolipid.

7. The composition of any one of claims 1 to 6, wherein the glycerolipid comprises only medium chain length fatty acids.

8. The composition of claim 7, wherein the medium chain length fatty acids comprise caprylic acid.

9. The composition of claim 8, wherein the caprylic acid comprises >50% w/w of the total fatty acid content of the glycerolipid.

10. The composition of claim 8 or claim 9, wherein the caprylic acid comprises about 55% to about 99% w/w of the total fatty acid content of the glycerolipid.

1 1 . The composition of any one of claims 7 to 10, wherein the medium chain length fatty acids comprise capric acid.

12. The composition of claim 1 1 , wherein the capric acid comprises < 50% w/w of the total fatty acid content of the glycerolipid.

13. The composition of claim 1 1 or claim 12, wherein the capric acid comprises about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid.

14. The composition of any one of claims 1 to 13, wherein the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.

15. The composition of any one of claims 1 to 14, wherein the antimicrobial agent is an antibiotic.

16. A composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) an antibiotic,

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.

17. The composition of claim 15 or claim 16, wherein 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.

18. The composition of any one of claims 15 to 17, wherein the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.

19. The composition of any one of claims 15 to 17, wherein the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.

20. The composition of any one of claims 1 to 14, wherein the antimicrobial agent is an antiseptic.

21 . A composition comprising:

(i) a glycerolipid; and

(ii) an antiseptic,

22. The composition of claim 21 , wherein the composition is suitable for administration to a subject.

23. The composition of any one of claims 20 to 22, wherein the antiseptic is chlorhexidine.

24. The composition of any one of claims 1 to 14, wherein the antimicrobial agent is an antifungal.

25. A composition suitable for administration to a subject, the composition comprising:

(i) a glycerolipid; and

(ii) an antifungal,

26. The composition of claim 24 or claim 25, wherein the antifungal is selected from an azole and/or amphotericin B.

27. The composition of any one of claims 1 to 26, wherein the composition is in the form of a liquid, gel, paste, cream, powder, or aerosol.

28. The composition of any one of claims 1 to 27, wherein the composition is formulated for topical administration to the subject.

29. The composition of any one of claims 1 to 28, wherein the glycerolipid potentiates the activity of the antimicrobial agent for the treatment or prevention of an infection in the subject.

30. The composition of claim 29, wherein the subject has become resistant to the antimicrobial agent when administered in the absence of the glycerolipid.

31 . The composition of claim 29 or claim 30, wherein the infection is a bacterial infection.

32. The composition of claim 31 , wherein the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis.

33. The composition of claim 31 , wherein the bacterial infection is due to MRSA.

34. The composition of any one of claims 31 to 33, wherein the bacterial infection forms part of a biofilm.

35. The composition of any one of claims 31 to 34, wherein the bacterial infection comprises an infected wound.

36. The composition of claim 29 or claim 30, wherein the infection is a fungal infection.

37. The composition of claim 36, wherein the fungal infection is due to Candida albicans.

38. The composition of any one of claims 1 to 37, wherein the subject is a human or an animal.

39. 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.

40. The method of claim 39, wherein the monoglyceride content of the glycerolipid is about 45% to about 100% w/w of the total glyceride content of the glycerolipid.

41 . The method of claim 39 or claim 40, wherein the monoglyceride content of the glycerolipid is about 45% to about 75% w/w of the total glyceride content of the glycerolipid.

42. The method of any one of claims 39 to 41 , wherein the monoglyceride content of the glycerolipid is about 50% to about 60% w/w of the total glyceride content of the glycerolipid.

43. The method of any one of claims 39 to 42, wherein the diglyceride content of the glycerolipid is 20% to 50% w/w of the total glyceride content of the glycerolipid.

44. The method of any one of claims 39 to 43, wherein the diglyceride content of the glycerolipid is about 32% to about 40% w/w of the total glyceride content of the glycerolipid.

45. The method of any one of claims 39 to 44, wherein the glycerolipid comprises only medium chain length fatty acids.

46. The method of claim 45, wherein the medium chain length fatty acids comprise caprylic acid.

47. The method of claim 46, wherein the caprylic acid comprises >50% w/w of the total fatty acid content of the glycerolipid.

48. The method of claim 46 or claim 47, wherein the caprylic acid comprises about 55% to about 99% w/w of the total fatty acid content of the glycerolipid.

49. The method of any one of claims 45 to 48, wherein the medium chain length fatty acids comprise capric acid.

50. The method of claim 49, wherein the capric acid comprises <50% w/w of the total fatty acid content of the glycerolipid.

51 . The method of claim 49 or claim 50, wherein the capric acid comprises about 1 % to about 42% w/w of the total fatty acid content of the glycerolipid.

52. The method of any one of claims 39 to 51 , wherein the glycerolipid is selected from the group consisting of Capmul MCM, Capmul MCM C8, Capmul MCM C10, Imwitor 742 and Imwitor 988.

53. The method of any one of claims 39 to 52, wherein the antimicrobial agent is an antibiotic.

54. 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 antibiotic, 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.

55. The method of claim 53 or claim 54, wherein 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.

56. The method of any one of claims 53 to 55, wherein the antibiotic is selected from one or more of a cephalosporin, an aminoglycoside, a glycopeptide, a carbapenem, a macrolide, a quinolone, and a phenicol.

57. The method of any one of claims 53 to 56, wherein the antibiotic is selected from one or more of cefepime, cefazolin, gentamicin, chloramphenicol, vancomycin, colistin, tobramycin, meropenem, bacitracin, erythromycin, ciprofloxacin, and amikacin.

58. The method of any one of claims 39 to 52, wherein the antimicrobial agent is an antiseptic.

59. 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 antiseptic, wherein 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.

60. The method of claim 58 or claim 59, wherein the antiseptic is chlorhexidine.

61 . The method of any one of claims 39 to 52, wherein the antimicrobial agent is an antifungal.

62. 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 antifungal, wherein 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.

63. The method of claim 61 or claim 62, wherein the antifungal is selected from an azole and/or amphotericin B.

64. The method of any one of claims 39 to 63, wherein the composition is in the form of a liquid, gel, paste, cream, powder, or aerosol.

65. The method of any one of claims 39 to 64, wherein the composition is topically administered to the subject.

66. The method of any one of claims 39 to 65, wherein the infection has become resistant to the antimicrobial agent when administered in the absence of the glycerolipid.

67. The method of any one of claims 39 to 66, wherein the infection is a bacterial infection.

68. The method of claim 67, wherein the bacterial infection is due to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Staphylococcus epidermidis, and/or Enterococcus faecalis.

69. The method of claim 67, wherein the bacterial infection is due to MRSA.

70. The method of any one of claims 67 to 69, wherein the bacterial infection forms part of a biofilm.

71 . The method of any one of claims 67 to 70, wherein the bacterial infection comprises an infected wound.

72. The method of any one of claims 39 to 66, wherein the infection is a fungal infection.

73. The method of claim 72, wherein the fungal infection is due to Candida albicans.

74. The method of any one of claims 39 to 73, wherein the subject is a human or an animal.

75. 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.

76. A kit for use in, or when used for, the treatment or prevention of an infection in a subject, the kit comprising:

(i) a glycerolipid; and

(ii) an antimicrobial agent,

77. 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.

78. 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 antimicrobial agent, and wherein the triglyceride content of the glycerolipid is≤10% w/w of the total glyceride content of the glycerolipid.

79. 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 antimicrobial agent, and wherein the triglyceride content of the glycerolipid is≤10% w/w of the total glyceride content of the glycerolipid.

80. 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.

81 . 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 antimicrobial agent thereby reducing the dose of the antibiotic 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.

82. 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.

83. 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.

84. A method for reducing viability of a bacterium resistant to an antibiotic or antiseptic, 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.

85. 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.

86. 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.

87. 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.

88. 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.

89. 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.

90. 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.

91 . 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.

92. 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.

93. 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.

94. 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.