Honey combination therapies for skin and wound infections: A systematic review of the literature

Replaced AM with VoR 2020-11-24.Topical application of medical grade honey is recommended for the clinical management of wound infections. The suitability of honey as a wound healing agent is largely due to its antibacterial activity, immune modulatory properties, and biocompatibility. Despite the usefulness of honey in wound healing, chronic wound infections continue to be a global problem requiring new and improved therapeutic interventions. Several recent studies have investigated the effects of combining honey with other therapies or agents with the aim of finding more efficacious treatments. In this systematic review, the database PubMed was used to carry out a search of the scientific literature on the combined effects of honey and other therapies on antimicrobial activity and wound and skin healing. The search revealed that synergistic or additive antimicrobial effects were observed in vitro when honey was combined with antibiotics, bacteriophages, antimicrobial peptides, natural agents e.g. ginger or propolis and other treatment approaches such as the use of chitosan hydrogel. Outcomes depended on the type of honey, the combining agent or treatment and the microbial species or strain. Improved wound healing was also observed in vivo in mice when honey was combined with laser therapy or bacteriophage therapy. More clinical studies in humans are required to fully understand the effectiveness of honey combination therapies for the treatment of skin and wound infections.https://doi.org/10.2147/CCID.S28214313pubpu

Honey: a realistic antimicrobal for disorders of the skin

Resistance of pathogenic micro-organisms to antibiotics is a serious global health concern. In this review, research investigating the antimicrobial properties of honeys from around the world, against skin relevant microbes is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent microbicidal activity against dermatologically important microbes. Moreover, in vitro studies have shown that honey can reduce microbial pathogenicity as well as reverse anti-microbial resistance. Studies investigating the antimicrobial properties of honey in vivo have been more controversial. It is evident that innovative research is required to exploit the anti-microbial properties of honey for clinical use and to determine the efficacy of honey in the treatment of a range of skin disorders with a microbiological aetiolog

Influence of Subinhibitory Concentrations of Honey on Toxic Shock Syndrome Toxin -1 (TSST-1) Production by Two Strains of Staphylococcus Aureus

Antibiotic resistant bacteria are a worldwide health concern and it is essential to develop new antimicrobial agents to kill these bacteria and to reduce the use of antibiotics. Staphyloccus aureus (S.aureus) an important medical pathogen is responsible for many wound infections and up to 25% of all strains produce the toxic shock syndrome toxin (TSST-1) which stimulates the release of inflammatory cytokines which cause fever and shock. Here we report on the inhibition of two penicillin resistant TSST-1 producing strains of S.aureus by seven different honeys. Bacterial growth was reduced after 24 hours at 37oC, from 10.0 log 10 in the TSB growth control to less than 1.0 log 10 in Highland, Chilean and Manuka honey. TSST-1 production was reduced from 256ng/ml in the TSB growth control to less than 30 ng/ml in sub inhibitory concentrations of all honeys.sch_die[1] Lowy, F.D. 1998. Staphylococcus aureus infections. New England Journal of Medicine, 339 (8) pp.520-532. [2] Andrey, D.O., Renzoni, A., Monod, A.,Lew, D.P.,Ambrose.L.C and Kelly, W.L. 2010. Control of the Staphyloccocus aureus toxic shock tst promoter by the global regulator SarA. J of Bacteriology, 192 (22),pp 6077-6085. [3] Boyle-Vavra, S., Carey, R.B. and Daum, R.S. 2001. Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate. The Journal of Antimicrobial Chemotherapy, 48 (5) Nov, pp.617-625 [4] Qiu, J., Wang, D., Xiang, H., Feng, H., Jiang, Y., Xia, L., et al 2010. Subinhibitory concentrations of thymol reduce enterotoxins A and B and -hemolysin production in Staphylococcus aureus isolates. PLoS one, 5 (3) pp.e9736. [5] Werner, G., Strommenger, B. and Witte, W. 2008. Acquired vancomycin resistance in clinically relevant pathogens. Future Microbiology(95) 547-562. [6] Dinges, M.M., Orwin, P.M. and Schlievert, P.M. 2000. Exotoxins of Staphylococcus aureus. Clinical microbiology reviews, 13 (1) Jan, pp.16-34, table of contents. [7] Lappin.E and Ferguson.A.J .2009. toxic shock syndrome (TSS) is an acute , multi- system toxin-mediated illness . Lancet. Infectious diseases 9.(5) pp 281-290 [8] Miethke, T., Duschek, K., Wahl, C., Heeg, K. and Wagner, H. 1993. Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1. European Journal of Immunology, 23 (7) pp.1494-1500. [9] Kramer, S. 1954. Levey. An older pharmacopoeia. JAMA, 155 (1) pp.26. [10] George, N.M. and Cutting, K.F. 2007. Antibacterial honey (Medihoney): in-vitro activity against clinical isolates of MRSA, VRE, and other multiresistant Gram-negative organisms including Pseudomonas aeruginosa. Wounds, 19 (9) pp.231. [11] Molan, P.C. 2006. The evidence supporting the use of honey as a wound dressing. The international Journal of Lower Extremity Wounds, 5 (1) Mar, pp.40-54. [12] Kwakman, P.H., Te Velde, A.A., De Boer, L., Vandenbroucke-Grauls, C.M. and Zaat, S.A. 2011. Two major medicinal honeys have different mechanisms of bactericidal activity. PLoS One, 6 (3) pp.e17709. [13] Schneider, M., Coyle, S., Warnock, M., Gow, I. and Fyfe, L. 2012. Anti-Microbial Activity and Composition of Manuka and Portobello Honey. Phytotherapy Research, 27 (8) pp.1162-1168. [14] White Jr, J.W. 1957. The composition of honey . Bee World, 38 (3) pp57-66 [15] Adenekan,M.O., Amusa,N.A, Lawal,A.O and Okpeze,V.E. 2010. Physico-chemical and microbiological properties of honey samples .J of Microbiol Antimicrobiol ,2, (8),pp100-104 [16] Kwakman, P.H., te Velde, A.A., de Boer, L., Speijer, D., Vandenbroucke-Grauls, C.M. and Zaat, S.A. 2010. How honey kills bacteria. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24 (7) Jul, pp.2576-2582. [17] Khan, F., Hill, J., Kaehler, S., Allsopp, M. and Vuuren, S. 2014. Antimicrobial properties and isotope investigations of South African honey. Journal of Applied Microbiology, [18] Carnworth.R., Graham.E.M., Reynolds.K and Pollock.P.J 2013. The antimicrobial activity of honey against common would isolates. The Veterinary Journal.10.1016. [19] Fyfe,L, Armstrong.F and Stewart. J 1998. Inhibition of Listeria monocytogenes and Salmonella enteridits by combinations of plant essential oils and derivatives of benzoic acid ; the development of synergistic antimicrobial combinations. International Journal of Antimicrobial Agents .9. 195-199 [20] Smith-Palmer, A., Stewart, J. and Fyfe, L. 2002. Inhibition of Listeriolysin 0 and phosphatidylcholine specific production in Listeria monocytogenes by subinhibitory concentrations of plant essential oils, of plant essential oils on the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus. Journal of Medical Microbiology, 51 , pp567 [21] Smith-Palmer, A., Stewart, J. and Fyfe, L. 2004. Influence of subinhibitory concentrations of plant essential oils on the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus. Journal of Medical Microbiology, 53 (Pt 10) Oct, pp.1023-1027. [22] Kakonien, V., Maruka, A., Kornyova, O., Charczun, N., Ligor, M. and Buszewski, B. 2009. Quantitative and qualitative determination of phenolic compounds in honey. Chemin technologija, 52 (3) pp.74-80. [23] Benzie, I.F. and Strain, J. 1996. The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power-: the FRAP assay. Analytical Biochemistry, 239 (1) pp.70-76. [24] Singleton, V. and Rossi, J.A. 1965. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. American Journal of Enology and Viticulture, 16 (3) pp.144-158 [25] White Jr, J.W. and Subers, M.H. 1963. Studies on honey inhibine. 2. A chemical assay. J Apic Res, 2 pp.93-100. [26] Kwakman, P.H., Te Velde, A.A., De Boer, L., Vandenbroucke-Grauls, C.M. and Zaat, S.A. 2011. Two major medicinal honeys have different mechanisms of bactericidal activity. PLoS One, 6 (3) pp.e17709. [27] Jenkins, R.E., Burton, N., and Cooper, R. 2013. Proteomic and genomic analysis of methicillin-resistant Staphylococcus aureus (MRSA) exposed to manuka honey in vitro demonstrated down-regulation of virulence markers. Journal of Antimicrobial Chemtherapy, doi;10.1093. pp1-13 [28] James,J.F., Chu,M.C., Lee.L., Peck,S.A. ,McKissick,C., Sullivan, H., et al 1989. Effect of magnesium on in vitro production of toxic shock syndrome toxin-1 . Reviews in Infectious Disease .Supplement 1,S157-166. [29] Yarwood,J.M and Schlievert, P.M 2000. Oxygen and carbon dioxide regulation of toxic shock syndrome toxin1 production by Staphylococcus aureus MN8. Journal of Clinical Microbiology. 38 (5) pp1797-1803 [30] Chan,P.F and Foster.S.J 1998. The role of the environmental factors in the regulation of virulence -determinant expression in Staphylococcus aureus .Microbiology .144 (9)pp 2469-2479 [31] van Langevelde,P ., van Dissel,j.T., Meurs.C.J.C Renz,J. and Groeneveld,P.H.P 1997 Antimicrobial agents and Chemotherapy .41,(8) 1682-1685 [32] Jenkins, R.E. and Cooper, R. 2012. Synergy between oxacillin and manuka honey sensitizes methicillin-resistant Staphylococcus aureus to oxacillin. The Journal of Antimicrobial Chemotherapy, 67 (6) Jun, pp.1405-1407. [33] Cowan.M.M 1999. Plant products as antimicroibial agents . Clinical Microbiology Reviews, American Society of Microbiology, 12,(4) pp 564-582 l [34] Brudzynski, K., Abubaker, K. and Miotto, D. 2012. Unraveling a mechanism of honey antibacterial action: Polyphenol/H<sub>2</sub>O<sub>2</sub>-induced oxidative effect on bacterial cell growth and on DNA degradation. Food Chemistry, 133 (2) pp.329-336.3pub3971pub

Honey: A Therapeutic Agent for Disorders of the Skin

Problems with conventional treatments for a range of dermatological disorders have led scientists to search for new compounds of therapeutic value. Efforts have included the evaluation of natural products such as honey. Manuka honey, for example, has been scientifically recognised for its anti-microbial and wound healing properties and is now used clinically as a topical treatment for wound infections. In this review, scientific evidence for the effectiveness of honey in the treatment of wounds and other skin conditions is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent anti-microbial activity against skin relevant microbes. Moreover, a number of in vitro studies suggest that honey is able to modulate the skin immune system. Clinical research has shown honey to be efficacious in promoting the healing of partial thickness burn wounds while its effectiveness in the treatment of non-burn acute wounds and chronic wounds is conflicted. Published research investigating the efficacy of honey in the treatment of other types of skin disorders is limited. Nevertheless, positive effects have been reported, for example, kanuka honey from New Zealand was shown to have therapeutic value in the treatment of rosacea. Anti-carcinogenic effects of honey have also been observed in vitro and in a murine model of melanoma.  It can be concluded that honey is a biologically active and clinically interesting substance but more research is necessary for a comprehensive understanding of its medicinal value in dermatology.

A Randomised Double Blind Placebo Controlled Trial of a Nucleotide-Containing Supplement Nucell on Symptoms of Participants with the Common Cold - A Pilot Study

Objectives: To ascertain whether a nucleotide containing nutritional supplement Nucell attenuates self-reported symptoms of the common cold. Design: A randomised controlled trial. Setting: A University. Participants: Participants with self-reported symptoms of the common cold but otherwise healthy individuals. Intervention: Nucell capsules containing a yeast-based nucleotide preparation or placebo were provided over a 28 day period. Outcome Measures: Subjective ratings of symptoms were recorded by self-administered questionnaires using a nine-point scale. Salivary IgA concentrations were analysed from samples collected during the first 7 days and then at days 14,21 and 28 of supplementation. Total and white blood cell counts were also measured throughout the intervention. Results: Thirty-six participants completed the study. Nineteen received Nucell and 17 received the placebo. The mean age of participants was similar (29.8 + 2.5 in Nucell group v 30.7 + 2.7 in control group) and the time participants had been suffering from cold-related symptoms was not significantly different in each treatment group (2.5 + 0.40 days in Nucell v 2.9 + 0.47 days in control group). Severity of self-reported symptoms was significantly attenuated in the Nucell treated group in the first week of supplementation for questions asked with respect to taste, painful sinuses and earache (p< 0.05). Supplementation with Nucell did not adversely affect total or differential white blood counts. Conclusion: These results suggest that Nucell supplementation administered as a treatment for cold-related symptoms may reduce the severity of specific symptoms particularly in the early infective phase. In conclusion, Nucell supplementation may provide subjective relief of some cold-related symptoms and may be of significant benefit administered as a treatment in participants where sinus pain, earache and diminished taste are common symptoms.sch_diepub4363pu

Inhibition and changes in antibiotic sensitivity of bacteria cultured aerobically and anaerobically in four different medicinal honeys

The growing prevalence of bacterial antibiotic resistance has led to a rediscovery of the antimicrobial properties of honey. This study investigated the antibacterial activity in aerobic and anaerobic conditions, the effect on bacterial antibiotic sensitivity, and the composition of four medical-grade honeys Medihoney®, Comvita® Antibacterial Wound Gel™, Revamil® gel, and Surgihoney™RO®.A broth assay was used to assess the antibacterial activity of the honeys against Staphylococcus aureus and Pseudomonas aeruginosa in aerobic and anaerobic conditions. A disk diffusion test was used to investigate the effect of exposure to a subinhibitory concentration of the honeys to the sensitivity of bacteria to a range of antibiotics. The composition of each honey was characterised by measuring: sugar content, pH, hydrogen peroxide activity, total polyphenolic content and antioxidant capacity.The honeys differed widely in antibacterial activity. Medihoney® was the most effective reducing the growth of both bacteria to < 1 compared to 9 log10 cfu/mL in the growth controls at all tested concentrations. Revamil® gel was the least active of the honeys only having a negligible effect on bacterial growth at the 25% honey concentration. All honeys were equally or more active in anaerobic conditions than in aerobic conditions. The polyphenolic content may influence the activity of honey. Various honey-antibiotic combinations were identified that enhanced antibiotic sensitivity in bacteria. More research is needed to clarify the role of polyphenols in honey activity and further explore the potential synergies between the honeys and antibiotics.1pubpub

Influence of sub-inhibitory concentrations of plant essential oils on the production of enterotoxins A and B and alpha toxin by Staphylococcus aureus

The data presented show the ability of subinhibitory concentrations of plant essential oils to influence the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus. Subinhibitory concentrations of the oils of bay, clove, cinnamon, nutmeg and thyme had no significant effect on the overall quantity of extracellular protein produced. Haemolysis due to alpha-toxin was significantly reduced after culture with all five plant essential oils. This reduction was greatest with the oils of bay, cinnamon and clove. These three oils also significantly decreased the production of enterotoxin A; the oils of clove and cinnamon also significantly decreased the production of enterotoxin B.Paper adds to the growing body of evidence that children can acquire phonological systems before they are able to master the phonetic skills needed to convey the contrasts in that systemsch_die53pub2931pub1

Inhibition of listeriolypin O and phosphatidylcholine - specific phospholipase C production in Listeria monocytogeres by subinhibitory concentrations of plant essential oils

Successful infection by Listeria monocytogenes is dependent upon a range of bacterial extracellular proteins including a cytolysin termed listeriolysin O and phosphatidylcholine-specific phospholipase C. Five plant essential oils--bay, clove, cinnamon, nutmeg and thyme--significantly reduced the production of listeriolysin O by L. monocytogenes. The greatest change was observed after culture with oil of thyme, which reduced haemolysis to 52.1 haemolytic units (HU)/ml compared with 99.8 HU/ml observed with the control. Oil of clove was the only oil that also significantly reduced phosphatidylcholine-specific phospholipase C activity. These changes were observed despite the oils causing no change to the final bacterial concentration or total extracellular protein concentration.sch_die51pub2932pub

Honey: A Therapeutic Agent for Disorders of the Skin

Problems with conventional treatments for a range of dermatological disorders have led scientists to search for new compounds of therapeutic value. Efforts have included the evaluation of natural products such as honey. Manuka honey, for example, has been scientifically recognised for its anti-microbial and wound healing properties and is now used clinically as a topical treatment for wound infections. In this review, scientific evidence for the effectiveness of honey in the treatment of wounds and other skin conditions is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent anti-microbial activity against skin relevant microbes. Moreover, a number of in vitro studies suggest that honey is able to modulate the skin immune system. Clinical research has shown honey to be efficacious in promoting the healing of partial thickness burn wounds while its effectiveness in the treatment of non-burn acute wounds and chronic wounds is conflicted. Published research investigating the efficacy of honey in the treatment of other types of skin disorders is limited. Nevertheless, positive effects have been reported, for example, kanuka honey from New Zealand was shown to have therapeutic value in the treatment of rosacea. Anti-carcinogenic effects of honey have also been observed in vitro and in a murine model of melanoma. It can be concluded that honey is a biologically active and clinically interesting substance but more research is necessary for a comprehensive understanding of its medicinal value in dermatology.sch_die5pub4469pub