Antibacterial compositions comprising honey

Abstract

The present invention relates to honey, particularly to honey for use in preventing and / or treating an infection, preferably a bacterial infection by Streptococcus pneumoniae and / or Staphylococcus aureus. The present invention further relates to a composition suitable for oral administration and / or rectal administration and / or perineal administration and to a composition suitable for nasal administration and / or rectal administration and / or perineal administration, wherein the compositions comprise honey.

Description

[0001] Title: Antibacterial compositions comprising honey

[0002] Technical field

[0003] The present invention relates to compositions comprising honey, particularly to therapeutic compositions comprising honey. The present invention particularly relates to preventing and / or treating respiratory infections, especially caused by bacteria such as (Methicillin-resistant) Staphylococcus aureus and / or Streptococcus pneumoniae, or by viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza A and Influenza B.

[0004] Background of the invention

[0005] Respiratory infection, which typically affects the mucous membranes in the respiratory system (nose, mouth and airways), is frequent in both children and adults. Said infections may be chronic or acute and can be caused by a variety of pathogens, including bacteria. Two examples of bacteria involved with respiratory infection are Streptococcus pneumoniae and Staphylococcus aureus, which are among the most common causes of community-acquired and hospital-acquired pneumonia, respectively [Slupsky, Carolyn M., et al. Journal of proteome research 8.6 (2009): 3029-3036], To reduce the global burden of infectious diseases such as respiratory infection, antimicrobial agents are of great importance.

[0006] Honey has been used by humans since ancient times. It is not only valued as a nutritional product, but also for its medicinal properties. One of the most important findings relating to the medicinal use of honey, is its antibacterial activity against numerous bacteria, including Streptococcus pneumoniae and Staphylococcus aureus. Although not yet fully elucidated, factors such as the production of hydrogen peroxide (via glucose oxidase, which catalyses the oxidation of glucose to hydrogen peroxide), high osmolarity and low pH are nowadays considered to be important factors for honey’s antibacterial efficacy [Almasaudi, Saad. "The antibacterial activities of honey." Saudi Journal of Biological Sciences 28.4 (2021): 2188- 2196],

[0007] Despite its gained popularity in modern medicine, the use of honey is not yet widely applied and / or accepted in clinical setting. However, driven by its natural origin and its beneficial healing properties, honey has been subjected to a multitude of laboratory and clinical investigations during the past few decades. One of the challenges associated with using honey is related to its consistency, particularly to its stickiness and viscosity, which make it difficult to use. For this reason, several research efforts have been focusing on better delivery and application procedures of honey, such as described in US11154578B2, which provides a composition comprising honey in the form of a semi-solid cream and US9044489B2 which relates to diluted honey-comprising compositions. Other efforts that are widely reported on are aimed at better understanding honey’s bioactivity and / or enhancing the bioactivity of compositions comprising honey, for example by exploring synergistic effects between ingredients, as described in EP3856219A1.

[0008] While the beneficial properties of honey are recognized, optimal application of honey in treatment, as well as its comparative efficacy with existing therapies, remains insufficient. This is not only related to above-mentioned factors such as its challenging consistency and lack of understanding of its bioactive properties, but also to a lack of evidence and guidance on how and when to use honey in clinical setting.

[0009] Therefore, there is a need for better guidance on optimal use of honey in treating bacterial infections, particularly respiratory tract infections.

[0010] Summary of the invention

[0011] The present inventors have identified compositions comprising honey that exhibit antibacterial effects, particularly bacteriostatic effects against (Methicillin-resistant) Staphylococcus aureus and / or Streptococcus pneumoniae. More specifically, the present inventors have identified a composition comprising honey for oral administration and a composition comprising honey for nasal administration. Surprisingly, it was found that either composition can be used in combination with commonly used antibiotics, according to a surprisingly advantageous dosage scheme, leading to an immediate and prolonged protective and / or treatment efficacy against Staphylococcus aureus and / or Streptococcus pneumoniae, without periods of suboptimal efficacy, in comparison to when not combined with commonly used antibiotics according to the dosage regime. Moreover, the present inventors have surprisingly found that the bacteriostatic effect of use for honey is even further enhanced when the compositions according to the invention are administered at least both nasally and orally, preferably also rectally and / or at the perineum, and that this effect is beyond a mere additive effect.

[0012] More specifically, it was surprisingly found that both in the case of administering the compositions honey as well as in the case of administering commonly used antibiotics such as penicillin, there are periods of suboptimal protection. Importantly, it was found that these periods (to be seen starting from the moment of administration) do not overlap, offering the possibility of administering a combination according to a surprisingly advantageous dosage scheme, wherein first one, but ideally both of the compositions comprising honey are administered (i.e. both oral and nasal administration), and then second, in case infection is still present, continue with administration of suitable antibiotics. Apart from the surprisingly advantageous dosage scheme, the current invention further relates to reducing the use of antibiotics and / or to preventing resistance to antibiotics, especially to preventing resistance to antibiotics in an early stage of treatment.

[0013] Thus, honey can serve as a complementary treatment alongside traditional antibiotics, providing a potentiating effect that enhances antibiotic efficacy. This combination therapy not only increases the effectiveness of antibiotics but also offers an alternative in cases where antibiotics may prove ineffective. Moreover, the continuous use of honey, even in prolonged treatments, offers significant benefits, as it can be employed indefinitely without contributing to antibiotic resistance. This unique combination underscores the versatility and long-term viability of honey as both an alternative and supportive treatment in combating bacterial infections..

[0014] Detailed description of the invention

[0015] The present disclosure relates to honey for use in preventing and / or treating an infection, preferably a bacterial or viral infection, more preferably a bacterial infection by Streptococcus pneumoniae and / or Staphylococcus aureus, wherein the use comprises: a) providing the honey to a subject, preferably providing the honey by oral administration and / or nasal administration; b) within 1-48 hours after starting step a), determining if the subject has a(n) (bacterial) infection, preferably an infection by a Streptococcus pneumoniae and / or Staphylococcus aureus, c) if a (bacterial) infection is determined in step b), preferably if an infection by

[0016] Streptococcus pneumoniae and / or Staphylococcus aureus is determined in step b), (further) administering, preferably within 1-48 hours after starting step a), an antibiotic drug, preferably a single compound antibiotic drug, to the subject; wherein step b) and / or step c) of the use are preferred steps.

[0017] In the present disclosure, traditional use is also envisaged.

[0018] Herein, with the term ‘honey’ is meant a viscous substance produced by honeybees and other insects from the nectar of flowers. Whereas the composition of honey may vary due to factors such as floral source, origin and purity, generally honey has a content of 80-85% carbohydrates, 15-17% water, 0.3% proteins, 0.2% ashes and minor quantities of aminoacids, phenols, pigments and vitamins [Khan, Shahid Ullah, et al. Saudi journal of biological sciences 25.2 (2018): 320-325], Herein, diluted honey compositions and / or compositions comprising honey in addition to other components, are also encompassed. Honey can also be described as a hypertonic sugar solution. In an embodiment, the present disclosure may also relate to other hypertonic sugar solution for use according to the present disclosure.

[0019] In a preferred embodiment, the honey for use according to the present disclosure, relates to honey for use in preventing and / or treating any bacterial infection, preferably bacterial infections of the respiratory tract, which herein refer to bacterial infections affecting the nose, mouth and / or airways. The honey for use may be used in preventing and or treating bacterial infections by any of the bacteria from the list consisting of, but not limited to: Streptococcus species such as Streptococcus pneumoniae, or Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Staphylococcus species such as Staphylococcus aureus, or Klebsiella pneumoniae, Pseudomonas aeruginosa, Moraxella catarrhalis, Bordetella pertussis, Streptococcus pyogenes (Group A Streptococcus), Corynebacterium diphtheriae, Neisseria meningitidis, Acinetobacter baumannii, Burkholderia cepacia, or any combination thereof.

[0020] In addition or alternative to its antibacterial properties, the honey for use according to the present disclosure can also be employed in the prevention and / or treatment of viral infections, particularly those affecting the respiratory tract. Such viral infections include, but are not limited to, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes COVID-19, Influenza A and Influenza B viruses responsible for seasonal flu, as well as respiratory viruses such as Rhinovirus and Respiratory Syncytial Virus (RSV), Human parainfluenza viruses (HPIVs). These viruses typically affect the nose, mouth, and airways, causing a range of symptoms from mild upper respiratory tract infections to severe pneumonia. The present disclosure provides antiviral potential is likely linked to the honey forming a protective barrier on mucosal surfaces, and / or its ability to modulate immune responses, thus providing a supportive role in reducing viral load and enhancing the body's natural defenses. This allows for inclusion in therapeutic strategies, particularly for the prevention of viral transmission or in the early stages of viral infection to mitigate symptoms and hasten recovery.

[0021] In addition or alternatively, also other types of infections are foreseen, such as fungal infections, for example due to Aspergillus fumigatus, or Candida albicans. These are also foreseen as targets of the treatment / prevention strategy as disclosed herein.

[0022] In another preferred embodiment, the honey for use according to the present disclosure is provided at least 1 time daily, preferably 2 times daily, even more preferably at least 3 times daily, yet even more preferably at least 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24 times daily in step a). In addition and / or alternatively, the honey is provided as often as appropriate, preferably at most 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 times daily. In addition and / or alternatively, the honey may be provided every 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours. In addition and / or alternatively, the honey may be provided for as long as desired in step a), preferably for at least 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 hours after step a). In addition and / or alternatively, the honey may be provided for at most 14, 12, 10, 8, 6, 4 days, preferably for at most 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 66 hours. It is preferred that in step a), no single compound or other antibiotic (other than honey) is administered.

[0023] In another preferred embodiment, the subject of step a) of the present disclosure may be a carrier i.e. the subject of step a) of the present disclosure may be harboring a potential pathogen e.g. bacteria, preferably Streptococcus pneumoniae and / or Staphylococcus aureus, but not showing signs and / or symptoms of (bacterial) infection. In a particularly preferred embodiment, the subject of step a) of the present disclosure may be a farmer, preferably a pig farmer.

[0024] In another preferred embodiment, it is determined (diagnosed) in step b) of the present disclosure if the subject has a bacterial infection, wherein step b) may be performed within 2 weeks after starting step a), preferably within 1 week after starting step a), more preferably within 6, 5, 4, 3 days after step a), even more preferably within 6-48, 8-48, 10-48, 12-48, 14- 48, 16-48, 18-48, 20-48, 22-48, 24-48 hours after starting step a). The determination or diagnosis of step b) of the present disclosure may be performed using any method known in the art and known to the skilled person, which typically involves a combination of clinical evaluation and laboratory tests. The subject may for example undergo a physical examination, which may reveal signs associated with bacterial infections. Examples of such signs are fever, swelling, redness and localized pain. In addition to this, the subject may undergo blood tests, urine tests, cultures of samples from the infected site, wherein the infected site is preferably the nose, mouth and / or airways.

[0025] In yet another preferred embodiment, if a (bacterial) infection is determined in step b) of the present disclosure, an antibiotic drug is administered, preferably within 6, 5, 4, 3 days after step a), even more preferably within 6-48, 8-48, 10-48, 12-48, 14-48, 16-48, 18-48, 20-48, 22- 48, 24-48 hours after starting step a), most preferably within 1-48 hours after starting step a), to the subject, wherein the antibiotic drug can be any antibiotic drug known in the art to prevent and / or treat infection with the bacteria (potentially) causing the infection. Preferably, the antibiotic drug is selected from the list comprising penicillin, amoxicillin, ceftriaxone, macrolides (e.g., azithromycin, clarithromycin), ampicillin, ciprofloxacin, tetracyclines (e.g., doxycycline), fluoroquinolones (e.g., levofloxacin), vancomycin, clindamycin, linezolid, piperacillin-tazobactam, cefepime, meropenem, amoxicillin-clavulanate, cefixime, cefuroxime, rifampicin, cephalosporins and trimethoprim-sulfamethoxazole. In another preferred embodiment, the antibiotic drug is a single compound antibiotic drug, preferably selected from the group consisting of vancomycin, daptomycin, linezolid, penicillin, macrolides, clindamycin, cephalosporins, rifampicin. Preferably, the antibiotic drug is administered for as long as typically prescribed to prevent and / or appropriate to treat infection with said bacteria, according to any suitable dosing regimen. More preferably, the antibiotic drug is administered for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 days. In addition and / or alternatively, the antibiotic drug is administered for at most 30, 29, 2827, 26, 25, 24, 23, 22, 21 , 20, 19, 18, 17, 16, 15, 14, 13, 12, 11 , 10, 9, 8, 7, 6, 5, 4, 3 days. In addition and / or alternatively, the antibiotic drug is administered at least once every other day, preferably at least daily, more preferably at least twice daily, even more preferably at least three times daily. In addition and / or alternatively, the antibiotic drug is administered at most 4, 3, 2, 1 time(s) daily. In a preferred embodiment, the antibiotic drug may be administered via any administration route known in the art, preferably via oral administration, via intravenous administration, topical administration and / or by inhaling. Preferably, if a (bacterial) infection is determined in step b) of the present disclosure, the antibiotic drug of step c) replaces the honey of the present disclosure i.e. the subject discontinuous to be provided with the honey. More preferably, if a (bacterial) infection is determined in step b) of the present disclosure, the antibiotic drug of step c) is further administered to the subject i.e. while the subject continuous to be provided with the honey of the present disclosure.

[0026] In a preferred embodiment, the honey according to the present disclosure is in step a) provided by both oral administration and nasal administration to a subject.

[0027] In addition and / or alternatively, the honey according to the present disclosure is used in preventing and / or treating bacterial infections of Streptococcus pneumoniae and / or Methicillin-resistant Staphylococcus aureus (MRSA).

[0028] Also foreseen in the present disclosure is a use wherein in step a) of the present disclosure an antibiotic drug is provided instead of honey, and / or in step c) of the present disclosure honey is administered instead of an antibiotic drug.

[0029] In a preferred embodiment, the honey for use according to the present disclosure is comprised in a composition, preferably in a composition (suitable) for oral administration and / or a composition (suitable) for nasal administration. In an embodiment, the honey according to the present disclosure, when provided by oral administration in step a), preferably comprises administering a composition for oral administration comprising the honey to the oral cavity and / or throat of the subject. Herein, oral administration includes, but is not limited to, (oral) inhalation. In another embodiment, the honey according to the present disclosure, when provided by nasal administration in step a), preferably comprises administering a composition for nasal administration comprising the honey to any part of the subjects nose. In a preferred embodiment, the honey, when provided by nasal administration, comprises administering the honey to the nose cavity and / or nostril(s) and / or nasal alar rim and / or nasal alar sill.

[0030] In a preferred embodiment, the composition for oral administration according to the present disclosure has a pH of lower than 7, preferably lower than 6, more preferably lower than 5, most preferably lower than or equal to 4.5. In a preferred embodiment, the composition for oral administration has a pH of at least 1, 2, 2.5, 2.75, 3, 3.5, 3.75, 4. In another preferred embodiment, the composition for oral administration according the present disclosure has a pH between preferably between 1-5, preferably between 2-4, more preferably between 2.5- 4.5, most preferably between 3-4.5. In addition and / or alternatively, the composition for nasal administration according to the present disclosure preferably has a pH of 4 or higher, preferably a pH of at least 5, 5.5, 6. In a preferred embodiment, the composition for nasal administration has a pH of at most 10, 9, 8, 7.5, 7. In addition and / or alternatively, the composition for nasal administration according to the present disclosure preferably has a pH between 3-9, preferably between 4-9, more preferably between 5-9, yet even more preferably between 5-7, most preferably between 6-7.

[0031] In an embodiment, the composition for oral administration according to the present disclosure preferably further comprises agents with soothing and / or antibacterial properties, such as Althea officinalis, Glycyrrhiza glabra, Citrus aurantium, Foeniculum vulgare, Foeniculi aetheroleum, lllicium verum, Menthae piperitae aetheroleum, Pimpinella anisum, Salviae officinalis aetheroleum, Malva sylvestris, Primula elatior, Angelica archangelica, Calendula officinalis, Cetraria islandica, Drosera rotundifolia, Echinacea purpurea, Eucalyptus globulus, Eucalypti aetheroleum, Hyssopus officinalis, Levomentholum, Marrubium vulgare, Menthae arvensis aetheroleum, Matricaria recutita, Pimpinella saxifrage, Pimpinella major, Plantago lanceolata, Rosae x centifolia, Salvia officinalis, Thymus serpyllum, Thymus vulgaris, Thymus zygis, Tilia cordata, Tilia platyphyllos, Verbena officinalis, Verbascum denisiflorium, Verbascum phlomoides, Achillea millefolium, Alchemilla xanthochlora, Anisi aetheroleum, Hyssopus officinalis, Iris germanica, Limonis aetheroleum, Melissa officinalis, Mentha x piperita, Menthae arvensis, Salvia triloba, Salviae lavandulifoliae, Angelica archangelica, Echinacea purpurea, Levomentholum, Matricaria recutita, Pimpinella major, Pimpinella saxifrage, Pulmonaria officinalis, Rosae gallica, Rosae x centifolia, Salvia officinalis, Thymus zygis, Tilia cordata, Tilia platyphyllos, Verbascum denisiflorium, Verbascum phlomoides, Verbena officinalis, Veronica officinalis, Thymus serpyllum, Calendula officinalis, Cetraria islandica, Eucalypti aetheroleum, Eucalyptus globulus, Marrubium vulgare, Papaver rhoeas, Plantago lanceolata, Thymus vulgaris, Thymus zigis Primula veris, Thymol crystals, Populus nigra-Buds, Glycyrrhiza glabra-Roots, Verbascum thapsiforme, aloe vera, Grindelia robusta, chamomile, elderberry, and / or green tea and / or extracts thereof. In a particularly preferred embodiment, the composition for oral administration according to the present disclosure preferably further comprises Althea officinalis and / or an extract of Althea officinalis. Althaea officinalis is a plant belonging to the Malvaceae family and to the Althaea genus, known for its soothing properties.

[0032] In a preferred embodiment, the composition for oral administration comprises between 20-70 wt.% Althea officinalis and / or an extract of Althea officinalis, preferably between 30-65, more preferably 35-60, even more preferably between 40-60, most preferably between 45-55 wt.% Althea officinalis and / or an extract of Althea officinalis, wherein the wt.% is drawn on the total weight of the composition for oral administration. Preferably the composition for oral administration comprises at least 20 wt.% Althea officinalis and / or an extract of Althea officinalis, preferably at least 25, 30, 35, 40, 45, 50 wt.% Althea officinalis and / or an extract of Althea officinalis, wherein the wt.% is drawn on the total weight of the composition for oral administration. Preferably the composition suitable for oral administration comprises at most 75 wt.% Althea officinalis and / or an extract of Althea officinalis, preferably at most 70, 65, 60, 55 wt.% Althea officinalis and / or an extract of Althea officinalis, wherein the wt.% is drawn on the total weight of the composition for oral administration. In addition and / or alternatively, the composition for nasal administration according to the present disclosure preferably further comprises a tonicity adjusting agent such as glycerol, sodium chloride, dextrose, mannitol, sorbitol, potassium chloride and / or calcium chloride, preferably glycerol. In a preferred embodiment, the composition for nasal administration comprises between 20-75 wt.% glycerol, preferably between 30-70, more preferably between 40-65, most preferably 45-55 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration. Preferably the composition for nasal administration comprises at least 20 wt.% glycerol, preferably at least 25, 30, 35, 40 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration. Preferably the composition suitable for nasal administration comprises at most 80 wt.% glycerol, preferably at most 75, 70, 65, 60, 55, 50, 45 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration.

[0033] In an embodiment, the composition for oral administration according to the present disclosure preferably further comprises honey and Althea officinalis or extract thereof in a honey:Althea officinalis (or extract thereof) in a wt.% ratio between 4:1 and 1 :4, preferably between 3:1 and 1 :3, more preferably between 1:1 and 1:3, even more preferably between 1:1 and 1 :2. In addition and / or alternatively, the composition for nasal administration according to the present disclosure preferably comprises honey and glycerol in a wt.% ratio between 1:1 and 4:1 , preferably between 1:1 and 3:1 , more preferably between 1 :1 and 2:1 , most preferably between 1 :1 and 1.5:1.

[0034] In an embodiment, the composition for oral administration and / or the composition for nasal administration according the present disclosure preferably further comprise(s) one or more preservative(s). Preferably, the composition for oral administration comprises less than 1 wt.% of preservative(s), preferably less than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 , 0.05, 0.02, wherein the wt.% is drawn on the total weight of the composition for oral administration. In addition and / or alternatively, the composition for oral administration preferably comprises at most 1 wt.% of one or more preservative, preferably at most 0.5, 0.3, 0.1, 0.05, 0.03, 0.02, 0.01 wt.% of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for oral administration. Preferably, the composition for nasal administration comprises less than 1 wt.% of preservatives, preferably less than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, wherein the wt.% is drawn on the total weight of the composition for nasal administration. In addition and / or alternatively, the composition for nasal administration preferably comprises at most 1 wt.% of one or more preservative, preferably at most 0.5, 0.3, 0.1, 0.05, 0.03, 0.02, 0.01 wt.% of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for nasal administration. Selection of specifically a composition for oral administration and / or a composition for nasal administration with a pH lower than 7, preferably lower than 6, 5, 4.5, more preferably a pH between 2.5-4.5 for the composition for oral administration and / or a pH between 5-7 for the composition for nasal administration, may allow for less than 1 , 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, 0.02 wt.% preservatives.

[0035] In an embodiment, the composition for oral administration and / or the composition for nasal administration comprise(s) one or more preservative(s) selected from the group consisting of benzoic acid, flavonoids, parabens, phenolic acids, abscisic acid, sorbic acid and pharmaceutically acceptable salts and combinations thereof, such as potassium sorbate. Preferably the composition for oral administration comprises at least two preservative(s), wherein the at least two preservatives comprise potassium sorbate and / or sodium benzoate. In addition and / or alternatively, the composition for nasal administration comprises at least one preservative(s), wherein the preservative comprises potassium sorbate.

[0036] In an embodiment, the composition for oral administration according to the present disclosure can be in any form known to the person skilled in the art, such as in lozenges or troches, in the form of a spray, an inhalation liquid, a gargle, syrup, pastille, and / or dissolvable strips, but is preferably in liquid form, preferably in the form of a spray. In addition and / or alternatively, the composition for nasal administration according to the present disclosure can be in any form known to the person skilled in the art, such as a spray, drops, balm, cream, lotion, salve, gels, ointments, powder, strips, wipes, foams and / or patches, but is preferably in the form of a cream and / or ointment and / or salve.

[0037] In an embodiment, the honey according to the present disclosure is, in step a), when provided by nasal administration to a subject, preferably provided via a carrier, wherein the carrier is suitable for conforming to the (human) nose cavity and / or nostrils and / or wherein the carrier is a porous adsorbent substance, preferably a sponge. In a preferred embodiment, the carrier comprises a fibrous network, which, is able to adsorb and / or absorb the honey through its outer surface and into the inner network. In addition and / or alternatively, the carrier releases the honey upon compression. In addition and / or alternatively, the carrier may comprise any suitable natural or synthetically manufactured absorbent material, preferably polyvinyl alcohol, as long as the carrier retains the capacity to generally hold its shape and preferably expand slightly when absorbing the honey through the outer surface. Preferably, the carrier is both rigid and flexible enough to allow manipulation during insertion of the carrier into the nose cavity and / or nostrils and removal therefrom. Surprisingly, the current inventors found that providing the honey via the carrier, provides superior results compared to when providing the honey via another means, such as by hand and or with a typical cotton swab. Without being bound to theory, this superior result is thought to be related to optimal delivery of honey to nose (i.e. nose cavity and / or nostril) contact, without discomfort, such as pain or a running and / or dripping nose. In addition / alternatively, providing the honey via the carrier may enhance therapeutic adherence.

[0038] In an embodiment, the honey according to the present disclosure preferably further comprises in step a), providing the honey by rectal administration and / or perineal administration to the subject and / or administering a composition comprising the honey to the rectum and / or perineum of the subject. Herein, rectal administration preferably refers to administration on and / or around the rectum, preferably not to internal administration via and in the rectum (i.e. enteral rectal administration) of the subject of step a) of the present disclosure. The perineal administration as described herein may be in the context of treating medical conditions such as hemorrhoids, anal fissures, anal abscesses, anal fistulas, etc. The present disclosure may include administration to any region of the body where there is a transition from dry to moist (wet).

[0039] In an embodiment, the honey according to the present disclosure can be any honey, preferably selected from the group consisting of acacia honey, manuka honey, clover honey, wildflower honey, alfalfa honey, buckwheat honey, eucalyptus honey, orange blossom honey and / or any combination thereof, preferably any honey originated from the European Union and / or South-America.

[0040] In addition to the above, the present disclosure further provides for the following steps: a) providing the honey by oral administration and / or nasal administration and / or rectal administration and / or perineal administration to at least 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500 subjects; b)within 1-48 hours after starting step a), determining if the subjects have an infection by

[0041] Streptococcus pneumoniae and / or (Methicillin-resistant) Staphylococcus aureus, c) determining an infection by Streptococcus pneumoniae and / or (Methicillin-resistant)

[0042] Staphylococcus aureus in at least one subject; d)administering, preferably within 1-48 hours after starting step a), an antibiotic drug to the at least one subject determined to have infection by Streptococcus pneumoniae and / or (Methicillin-resistant) Staphylococcus aureus.

[0043] Also foreseen is a method for prevention or treatment of an infection, preferably a bacterial infection, more preferably an infection by Streptococcus pneumoniae and / or Staphylococcus aureus, e.g. for a subject in need thereof, the method comprising the steps as disclosed herein.

[0044] The present disclosure further relates to a composition suitable for oral and / or rectal administration and / or perineal administration, wherein the composition preferably comprises:

[0045] - honey;

[0046] - one or more preservative(s) and / or;

[0047] - one or more of the agents with soothing and / or antibacterial properties, preferably Althea officinalis and / or an extract of Althea officinalis, more preferably a combination of Althea officinalis (and / or an extract of Althea officinalis) and Thymus vulgaris. Said composition for oral and / or rectal administration and / or perineal administration may also be used in the form of a nasal spray.

[0048] Preferably, the composition suitable for oral administration and / or rectal administration and / or perineal administration according to the present disclosure comprises between 1-70 wt.% of honey, preferably between 2-65, more preferably between 3-60, even more preferably between yet even more preferably between 5-55, yet even more preferably between 10-50 most preferably between 20-40 wt.% of honey, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. In another preferred embodiment, the composition suitable for oral administration and / or rectal administration and / or perineal administration comprises at least 10, 20, 25, 30, 31, 32, 33, 34, 35, 36 wt.% honey, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. In addition and / or alternatively, the composition suitable for oral administration and / or rectal administration and / or perineal administration comprises at most 100, 90, 80, 85, 80, 75, 70, 65, 60, 55, 50, 45 wt.% honey, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration.

[0049] The composition suitable for oral administration and / or rectal administration and / or perineal administration according to the present disclosure may additionally and / or alternatively comprise one or more preservative(s). Preferably, the composition suitable for oral administration and / or rectal administration and / or perineal administration comprise(s) between 0.001-5 wt.% of one or more preservative(s), preferably between 0.005-3, more preferably between 0.01-2, most preferably between 0.01-1, most preferably between 0.01- 0.1 wt.% of one or more preservative(s). Preferably, the composition for oral administration and / or rectal administration and / or perineal administration comprise(s) one or more preservative(s) selected from the group consisting of benzoic acid, flavonoids, parabens, phenolic acids, abscisic acid, sorbic acid and pharmaceutically acceptable salts and combinations thereof, such as potassium sorbate. Preferably, the composition for oral administration and / or rectal administration and / or perineal administration comprises less than 1 wt.% of preservative(s), preferably less than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 , 0.05, 0.02 of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. In addition and / or alternatively, the composition for oral administration and / or rectal administration and / or perineal administration preferably comprises at most 1 wt.% of one or more preservative, preferably at most 0.5, 0.3, 0.1, 0.05, 0.03, 0.02, 0.01 wt.% of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration.

[0050] The composition suitable for oral administration and / or rectal administration and / or perineal administration according to the present disclosure may additionally and / or alternatively comprise(s) one or more of the agents with soothing and / or antibacterial properties. Preferably, the composition suitable for oral administration and / or rectal administration and / or perineal administration comprises between 20-70 wt.% of one or more of the agents with soothing and / or antibacterial properties, preferably between 30-65, more preferably 35-60, even more preferably between 40-60, most preferably between 45-55 wt.% of one or more of the agents with soothing and / or antibacterial properties, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. Preferably the composition suitable for oral administration and / or rectal administration and / or perineal administration comprises at least 20 wt.% of one or more of the agents with soothing and / or antibacterial properties, preferably at least 25, 30, 35, 40, 45, 50 wt.% of one or more of the agents with soothing and / or antibacterial properties, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. Preferably the composition suitable for oral administration and / or rectal administration and / or perineal administration comprises at most 75 wt.% of one or more of the agents with soothing and / or antibacterial properties, preferably at most 70, 65, 60, 55 wt.% of one or more agents of the with soothing and / or antibacterial properties, wherein the wt.% is drawn on the total weight of the composition for oral administration and / or rectal administration and / or perineal administration. In addition and / or alternatively, the one or more agents with soothing and / or antibacterial properties comprise(s) at least Althea officinalis and / or an extract of Althea officinalis.

[0051] Preferably, the composition suitable for oral administration and / or rectal administration and / or perineal administration has a pH of lower than 7, preferably lower than 6, more preferably lower than 5, most preferably lower than or equal to 4.5. In a preferred embodiment, the composition for oral administration and / or rectal administration and / or perineal administration has a pH of at least 1, 2, 2.5, 2.75, 3, 3.5, 3.75, 4. In another preferred embodiment, the composition for oral administration and / or rectal administration and / or perineal administration according the present disclosure has a pH between preferably between 1-5, preferably between 2-4, more preferably between 2.5-4.5, most preferably between 3-4.5.

[0052] The present disclosure further relates to a composition suitable for nasal and / or rectal administration and / or perineal administration, wherein the composition preferably comprises:

[0053] - honey; preservatives and / or; glycerol.

[0054] Preferably, the composition suitable for nasal administration and / or rectal administration and / or perineal administration according to the present disclosure comprises between 1-70 wt.% of honey, preferably between 3-65, more preferably between 5-60, even more preferably between yet even more preferably between 10-55, yet even more preferably between 20-50 most preferably between 30 and 40 wt.% of honey, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration. In another preferred embodiment, the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprises at least 10, 20, 25, 30, 31 , 32, 33, 34, 35, 36 wt.% honey, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration. In addition and / or alternatively, the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprises at most 100, 90, 80, 85, 80, 75, 70, 65, 60, 55, 50, 45 wt.% honey, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration.

[0055] The composition suitable for nasal administration and / or rectal administration and / or perineal administration according to the present disclosure may additionally and / or alternatively comprise one or more preservative(s). Preferably, the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprise(s) between 0.001-5 wt.% of one or more preservative(s), preferably between 0.005-3, more preferably between 0.01-2, most preferably between 0.01-1, most preferably between 0.01- 0.1 wt.% of one or more preservative(s). Preferably, the composition for nasal administration and / or rectal administration and / or perineal administration comprise(s) one or more preservative(s) selected from the group consisting of benzoic acid, flavonoids, parabens, phenolic acids, abscisic acid, sorbic acid and pharmaceutically acceptable salts and combinations thereof, or any combination thereof, such as potassium sorbate. Preferably, the composition for nasal administration and / or rectal administration and / or perineal administration comprises less than 1 wt.% of preservative(s), preferably less than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 , 0.05, 0.02 of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration. In addition and / or alternatively, the composition for nasal administration and / or rectal administration and / or perineal administration preferably comprises at most 1 wt.% of one or more preservative, preferably at most 0.5, 0.3, 0.1, 0.05, 0.03, 0.02, 0.01 wt.% of one or more preservative, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration.

[0056] The composition suitable for nasal administration and / or rectal administration and / or perineal administration according to the present disclosure may additionally and / or alternatively comprise(s) glycerol. Preferably, the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprises between 20-75 wt.% glycerol, preferably between 30-70, more preferably between 40-65, most preferably 45-55 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration. Preferably the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprises at least 20 wt.% glycerol, preferably at least 25, 30, 35, 40 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration. Preferably the composition suitable for nasal administration and / or rectal administration and / or perineal administration comprises at most 80 wt.% glycerol, preferably at most 75, 70, 65, 60, 55, 50, 45 wt.% glycerol, wherein the wt.% is drawn on the total weight of the composition for nasal administration and / or rectal administration and / or perineal administration.

[0057] Preferably, the composition suitable for nasal administration and / or rectal administration and / or perineal administration has a pH of 4 or higher, preferably a pH of at least 5, 5.5, 6. In a preferred embodiment, the composition for nasal administration and / or rectal administration and / or perineal administration has a pH of at most 10, 9, 8, 7.5, 7. In addition and / or alternatively, the composition for nasal administration and / or rectal administration and / or perineal administration according to the present disclosure preferably has a pH between 3-9, preferably between 4-9, more preferably between 5-9, yet even more preferably between 5-7, most preferably between 6-7.

[0058] The compositions as described herein preferably are for use in the prevention and / or treatment of bacterial infections or viral infections (or fungal infections), in particular as set out in detail herein. The composition, e.g. the composition suitable for oral administration and / or nasal administration may be administered in the form of vapor, particularly vapor for inhalation. Vapor administration offers a targeted method to deliver the active components of honey directly to the respiratory tract, providing an efficient and non-invasive approach for treating / preventing infections of the nose, mouth, airways, and lungs. The vaporized form allows for the rapid dispersion of the antibacterial and antiviral properties of honey over the mucosal surfaces of the respiratory tract, where it can act locally to inhibit pathogen growth / replication, reduce inflammation, and support the immune response.

[0059] To achieve vapor administration, the composition can optionally be aerosolized using a suitable device such as a nebulizer, vaporizer, or inhaler. Nebulizers work by converting liquid honey compositions into a fine mist, which can then be inhaled deeply into the lungs. Vaporizers, on the other hand, heat the composition to produce a vapor that can be inhaled into the nasal and oral cavities. Inhalers, typically used in asthma treatments, could be adapted to deliver small doses of vaporized honey compositions for targeted therapeutic effects. These devices offer a controlled and precise delivery of the composition, ensuring that the honey reaches the respiratory mucosa without being degraded or losing efficacy. Additionally, the use of vapor allows for widespread distribution across the respiratory tract, making it especially suitable for treating conditions like bronchitis, pneumonia, and other infections where the pathogen affects deeper areas of the airways and lungs. Vapor administration can be particularly beneficial in the early stages of respiratory infections, where localized application may prevent further spread of the pathogen and provide immediate relief from symptoms like congestion and irritation. Vapor administration may also offer advantages in terms of patient compliance, as it allows for easy and comfortable use, especially for individuals who may have difficulty swallowing oral formulations or for children and the elderly, where non-invasive methods are preferred.

[0060] It is also foreseen that the compositions suitable for oral and / or rectal administration and / or perineal administration and / or the composition suitable for nasal administration and / or rectal administration and / or perineal administration may further comprise additional ingredients, such as colorants or flavorings, preferably citrus and / or thyme (extract), which may further enhance the organoleptic properties of the compositions suitable for oral and / or rectal administration and / or perineal administration and / or the composition suitable for nasal administration and / or rectal administration and / or perineal administration.

[0061] Brief description of the figures

[0062] Figure 1. Box plots showing zone inhibition measurements of the disc diffusion test with the composition for oral use, the composition for nasal use, and an antibiotic after 24 and 48 hours of incubation of Streptococcus pneumoniae.

[0063] Figure 2. Box plots showing zone inhibition measurements of the disc diffusion test with the composition for oral use, the composition for nasal use, and an antibiotic after 24 and 48 hours of incubation of Staphylococcus aureus. Figure 3 shows graphical representation of 5 different tested Staphylococcus strains. 1. Gmel 80%, 2. Gmel 51.8%, 3. Gmel 13%, 4. Throatspray 80%, 5. Throatspray 51.8%, 6.

[0064] Throatspray 13%, 7. Honey 80%, 8. Honey 51.8%, 9. Honey 13%, 10. Althea / Thyme 80%, 11. Althea / Thyme 51.8%, 12. Althea / Thyme 13%, 13. Positive control, 14. Neg control Mer, 15. Neg. control Flu. The order of the columns is as shown: ATCC, JBZ1, JBZ2, JBZ3, JBZ4, JBZ5, controls.

[0065] Examples

[0066] Example 1. The effect of the composition for oral use and the composition for nasal use on the bacteriostatic activity of Streptococcus pneumoniae and Staphylococcus aureus

[0067] The aim of this experiment is to evaluate the antibacterial (i.e. bacteriostatic) activity of the composition for oral use with regard to Streptococcus pneumoniae and Staphylococcus aureus.

[0068] Method

[0069] The composition for oral administration and the composition for nasal administration were prepared as described in Table 1 and 2. The bacteriostatic activity was evaluated using a disc diffusion test. More specifically, a bacterial culture of Streptococcus pneumoniae and Staphylococcus aureus was inoculated on an agar surface, after which a filter disk impregnated with either of the composition for oral administration of the composition for nasal administration was placed on the agar surface. The agar plates were incubated for 24 and 48 hours, after which the zones of inhibition formed around each disk were measured. As a control, antibiotic penicillin was used.

[0070] Table 1 Table 2

[0071] Results

[0072] As can be seen in Figure 1, compared to penicillin, both the composition for oral administration and composition for nasal administration showed a clearly higher zone of inhibition for Streptococcus pneumoniae after 24 hours. After 48 hours, the zone of inhibition on the plates exposed to penicillin generally increased. However, the plates exposed to the composition for nasal administration, still showed a superior (i.e. higher) zone of inhibition compared to the plates exposed to penicillin. This effect was not shown for the composition for oral administration, which, although still showing a clear zone of inhibition (higher than for penicillin after 24 hours), had now a more narrow zone.

[0073] As can be seen in Figure 2, a similar trend was seen for the plates inoculated with Staphylococcus aureus, wherein after 24 hours, both the composition for oral administration and the composition for nasal administration showed a higher zone of inhibition than when penicillin was used. After 48 hours, this trend was still visible, with both the composition for oral administration and the composition for nasal administration having the highest zones of inhibition. As for Streptococcus pneumoniae, the composition for nasal administration showed superior over the composition for oral administration.

[0074] As can been seen from these experiments, both the composition for oral administration and the composition for nasal administration, as well as the antibiotic result in zones of inhibition, both for Streptococcus pneumoniae and for Staphylococcus aureus. Although the composition for oral administration and the composition for nasal administration show superior zones of inhibition compared to the antibiotic, the effect of the compositions reduces over the time span evaluated, whereas the effect of the antibiotic increases. Overall, the shown data suggests that either of the compositions comprising honey on their own, are ideal to use in the early phase of infection (as it shows immediate effect and is superior to antibiotics), after which it should be established in time whether (further) administration of antibiotics may be desirable. Example 2. Effect of nasal and oral administration

[0075] The aim of this experiment is to evaluate the effect of the administration route on the prevent symptoms associated with respiratory disease.

[0076] Methods

[0077] Before visiting hospital with known cases of Streptococcus pneumoniae infection, 80 human subjects are treated with either the composition for oral administration, the composition for nasal administration, or the both the composition for oral and nasal administration. As a control, a single-compound oral or nasal placebo was given. The composition(s) are administered three times daily. Vulnerable populations (i.e. children and older adults) are excluded from the study. Efficacy of the treatment is evaluated after 48 hours after commencement of the treatment, by means of physical examination, which includes evaluation of the following symptoms: fever, cough, chest pain, shortness of breath, difficulty breathing fatigue. The results of the physical examination are translated to scores, wherein:

[0078] - = several new cases of Streptococcus pneumoniae infection

[0079] + = few new cases of Streptococcus pneumoniae infection

[0080] +++ = no new cases of Streptococcus pneumoniae infection

[0081] Results

[0082] As can be seen from Table 3, individual administration of either the composition for oral administration or the composition for nasal administration results in acceptable results, improved compared to no treatment. Interestingly, when comparing treatment with both the composition for oral administration and the composition for nasal administration, even more superior results are obtained.

[0083] Table 3 Example 3. Effect of pH

[0084] The aim of this experiment is to evaluate the effect of pH on the antibacterial (i.e. bacteriostatic) activity of the composition for oral use (hereafter ‘oral’) and the composition for nasal use compositions (hereafter ‘nasal’).

[0085] Method

[0086] The composition for oral use and the composition for nasal use are prepared as described in Example 1 and subsequently aliquoted for each pH condition to be tested. The pH of each composition is adjusted using citric acid or sodium hydroxide (under control of a calibrated pH meter). The bacteriostatic activity is evaluated using a disc diffusion test. More specifically, a bacterial culture of Streptococcus pneumoniae is inoculated on an agar surface, after which a filter disk impregnated with either of the compositions is placed on the agar surface. The agar plates are incubated for 24 hours, after which the zones of inhibition formed around each disk are measured and translated to a score, wherein:

[0087] - = suboptimal zone of inhibition

[0088] + = acceptable zone of inhibition

[0089] ++ = good zone of inhibition n.d. = will not be determined

[0090] Result

[0091] As can be seen from table 4 for the oral composition, a pH between 2 and 6 results in acceptable to even good zones of inhibition. Based on the results, it seems that the oral composition performs best when having a pH between 3 and 5. Interestingly, for the nasal composition, the optimum pH values are slightly higher. In general, pH values between 4-8 result in acceptable to even good zones of inhibition. The best zones of inhibition are found when the composition comprises a pH between 5 and 7.

[0092] Table 4.

[0093] Example 4. Bacteriostatic effect of honey and / or antibiotics

[0094] The aim of this experiment is to evaluate the antibacterial (i.e. bacteriostatic) activity of the composition for oral use and / or an antibiotic with regard to Streptococcus pneumoniae over time.

[0095] Method

[0096] The bacteriostatic activity is evaluated using a disc diffusion test, for which a bacterial culture of Streptococcus pneumoniae is inoculated on an agar surface. A composition comprising honey is prepared as described in Example 1. A filter disk, previously impregnated with either of the compositions (prepared as in experiment 1), or a suitable antibiotic (e.g. penicillin) is placed on the agar surface. As can be seen in table 5, a combination of the composition comprising honey and an antibiotic is also evaluated. The agar plates are incubated for 72 hours, after which the zones of inhibition formed around each disk are measured and translated to a score, wherein:

[0097] - = suboptimal zone of inhibition + = acceptable zone of inhibition +++ = good zone of inhibition n.d. = will not be determined

[0098] Results

[0099] As can be seen from Table 5, both the composition comprising honey (i.e. ‘Honey’) and the antibiotic (i.e. ‘Antibiotic’) alone result in suboptimal zones of inhibition (i.e. bacteriostatic activity). Interestingly, the best results are obtained when combining both the composition comprising honey and the antibiotic. The results do not only show that it is the combination between the composition comprising honey and the antibiotic that result in superior results, but also that the timing matters. More specifically, when comparing dosing regimen number 2, 3, 5 and 6, it can be seen that acceptable results are obtained when the composition comprising honey is administered first (i.e. from the start). Interestingly, when said composition is administered first, after which a switch is made to antibiotics within 12-48 hours from the start, even better results are obtained.

[0100] Table 5

[0101] Example 5

[0102] Healthcare institutions are vulnerable to resistant bacteria such as MRSA, which is insensitive to most antibiotics. Honey-based products offer a promising solution to combat MRSA and reduce antibiotic resistance. The aim of this example was to investigate whether Gmel and Honey & Althea throat spray exhibit bacteriostatic activity against various clinical strains of Staphylococcus aureus, and to compare these effects with those of the antibiotics Meropenem and Flucioxacillin.

[0103] Figure 3 shows graphical representation of different tested Staphylococcus strains originating from the Jeroen Bosch Hospital (JBZ1-5) in Den Bosch (NL). 80% means 80% of the volume in the cuvet means 160 microliter H&A spray and 40 microliter medium with bacteria. 50% means 100 microliter H&A versus 100 microliter medium. 13% means 26 microliter H&A versus 174 microliter medium. The Honey & Althea throat spray contains Thyme to correct taste. Please note that in the Figure, Thyme is Althea / Thyme solution as it is a carrier for honey in the liquid.

[0104] Bacterial growth is best limited at lower dilution (<13%) with the different formulations, but with pure honey bacterial growth is also limited at higher dilutions (>13%). A possible explanation for this is that, even at higher dilution, pure honey remains more viscous, which inhibits bacterial growth, although this is not certain. A clinical disadvantage of using pure honey is that it is extremely sticky. The antibacterial effect of the formulations of G-Mel and the Honey & Althea Throat Spray, as well as the contribution of thyme in the throat spray, was also tested on different strains of Staphylococcus aureus in comparison to two antibiotics, i.e. negative control 1 is the antibiotic meropenem and negative control 2 is the antibiotic flucloxacilline.

Claims

CLAIMS1. Honey for use in preventing and / or treating an infection by Streptococcus pneumoniae and / or Staphylococcus aureus, wherein the use comprises: a)providing the honey by oral administration and / or nasal administration to a subject; b)within 12-48 hours after starting step a), determining if the subject has an infection byStreptococcus pneumoniae and / or Staphylococcus aureus, c) if an infection by Streptococcus pneumoniae and / or Staphylococcus aureus is determined in step b), administering, within 12-48 hours after starting step a), a single compound antibiotic drug to the subject.

2. Honey for use according to claim 1, wherein the honey in step a) is provided by oral administration and nasal administration.

3. Honey for use according to any one of claims 1 or 2, wherein the Staphylococcus aureus is Methicillin-resistant Staphylococcus aureus (MRSA).

4. Honey for use according to any one of claims 1 to 3, wherein:- the oral administration of step a) comprises administering a composition for oral administration comprising the honey to the oral cavity and / or throat of the subject; and / or- the nasal administration of step a) comprises administering a composition for nasal administration comprising the honey to the nose cavity and / or nostril(s) and / or nasal alar rim and / or nasal alar sill.

5. Honey for use according to any one of claims 1 to 4, wherein:- the oral administration of step a) comprises administering a composition for oral administration comprising the honey, wherein the composition for oral administration has a pH of lower than 5, preferably between 2.5-4.5; and / or- the nasal administration of step a) comprises administering a composition for nasal administration comprising the honey, wherein the composition for nasal administration has a pH of 5 or higher, preferably between 5-7.

6. Honey for use according to claim 5, wherein:- the composition for oral administration further comprises Althea officinalis and / or an extract of Althea officinalis; and / or- the composition for nasal administration further comprises glycerol.

7. Honey for use according to any one of claims 5 or 6, wherein:- the composition for oral administration comprises honey and Althea officinalis or extract thereof in a wt.% ratio between 3:1 and 1:3, preferably between 1:1 and 1 :3, more preferably between 1 :1 and 1:2; and / or- the composition for nasal administration comprises honey and glycerol in a wt.% ratio between 1 :1 and 3:1, preferably between 1:1 and 2:1 , most preferably between 1 :1 and 1.5:1; wherein the wt.% is drawn on the total weight of the composition.

8. Honey for use according to any one of claims 5 to 7, wherein the composition for oral administration and / or the composition for nasal administration further comprise(s) one or more preservative(s), wherein the wt.% of preservative(s) is less than 1 wt.%, preferably less than 0.5 wt.%, wherein the wt.% is drawn on the total weight of the composition.

9. Honey for use according to any one of claims 5 to 8, wherein :- the composition for oral administration comprises one or more preservative(s), wherein the preservatives comprise potassium sorbate and / or sodium benzoate;- the composition for nasal administration comprises one or more preservatives, wherein the preservatives comprise potassium sorbate.

10. Honey for use according to any one of claims 5 to 9, wherein:- the composition for oral administration is in liquid form, preferably in the form of a spray and / or inhalation liquid; and / or- the composition for nasal administration in the form of a gel, cream, ointment, balm, lotion and / or salve.

11. Honey for use according to any one of claims 1 to 10, wherein the nasal administration in step a) is via a carrier, wherein the carrier is suitable for conforming to the (human) nose cavity and / or nostrils, and / or wherein the carrier is a porous absorbent substance, preferably a sponge, preferably a sponge comprising polyvinyl alcohol.

12. Honey for use according to any one of claims 1 to 11 , wherein step a) further comprises providing the honey by rectal administration and / or perineal administration to the subject and / or wherein step a) comprises administering a composition comprising the honey to the rectum and / or perineum of the subject.

13. Honey for use according to any one of claims 1 to 12, wherein the honey is selected from the group consisting of acacia honey, manuka honey, clover honey, wildflower honey, alfalfa honey, buckwheat honey, eucalyptus honey, orange blossom honey and / or any combination thereof.

14. Honey for use according to any one of claims 1 to 13, wherein the use comprises: a) providing the honey by oral administration and / or nasal administration and / or rectal administration and / or perineal administration to at least 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500 subjects; b)within 12-48 hours after starting step a), determining if the subjects have an infection byStreptococcus pneumoniae and / or (Methicillin-resistant) Staphylococcus aureus, c) determining an infection by Streptococcus pneumoniae and / or (Methicillin-resistant)Staphylococcus aureus in at least one subject; djadministering a single compound antibiotic drug to the at least one subject determined to have infection by Streptococcus pneumoniae and / or (Methicillin-resistant) Staphylococcus aureus.

15. Honey for use according to any one of claims 1 to 14, wherein the single compound antibiotic drug is selected from the group consisting of vancomycin, daptomycin, linezolid, penicillins, macrolides, clindamycin, cephalosporins, rifampicin.

16. A composition suitable for oral administration administration comprising:- 5-60 wt.% honey;- 0.01-1 wt.% preservative(s);- 40-60 wt.% Althea officinalis and / or an extract of Althea officinalis; wherein the composition has a pH of between 2.5 and 4.5; wherein the wt.% is drawn on the total weight of the composition.

17. A composition suitable for nasal administration comprising:- 2-60 wt.% honey;- 0.01-1 wt.% preservative(s);- 30-60 wt.% glycerol; wherein the composition has a pH of between 5 and 7; wherein the wt.% is drawn on the total weight of the composition.

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