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Medical-grade Honey enriched with antimicrobial peptides has enhanced activity against antibiotic resistant

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Abstract

Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We investigated the kinetics of the killing of antibiotic-resistant bacteria by RS honey, the source for the production of Revamil® medical-grade honey, and we aimed to enhance the rapid bactericidal activity of RS honey by enrichment with its endogenous compounds or the addition of antimicrobial peptides (AMPs). RS honey killed antibiotic-resistant isolates of Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus faecium, and Burkholderia cepacia within 2 h, but lacked such rapid activity against methicillin-resistant S. aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. It was not feasible to enhance the rapid activity of RS honey by enrichment with endogenous compounds, but RS honey enriched with 75 μM of the synthetic peptide Bactericidal Peptide 2 (BP2) showed rapid bactericidal activity against all species tested, including MRSA and ESBL E. coli, at up to 10-20-fold dilution. RS honey enriched with BP2 rapidly killed all bacteria tested and had a broader spectrum of bactericidal activity than either BP2 or honey alone.
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... In addition to the unfavorable physicochemical parameters, honey contains peptides and proteins that exert antibacterial activity. Although bee defensin-1 peptide was firstly isolated from royal jelly, it has also been detected in the medical-grade honey Revamil®, in different honey types harvested in Slovakia as well as in eucalyptus honey samples from Ecuador (Kwakman et al., 2011;Proano et al., 2021;Valachova et al., 2016). Upon infection of bee larvae with a pathogen, bee defensin-1 (Def-1) (5.52 kDa) expression is induced in the fat body and then it is secreted into the haemolymph as a part of the innate immune response. ...
... The highest amount of defensin-1 was found in honey samples of multi-floral origin . Bee defensin-1 exerted antibacterial activity against diverse bacteria, such as isolates of P. aeruginosa, Staphylococcus epidermidis, S. aureus, Enterococcus faecium and Burkholderia cepacia (Kwakman et al., 2011;Valachova et al., 2016). Bee defensin-1 has a cationic character and exerts antimicrobial activity presumably initiated by an interaction with the negatively charged membranes of pathogens (Yeaman & Yount, 2003). ...
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Background Honey is considered as a functional food with health-promoting properties. Its potent antibacterial and antibiofilm effects are the major attributes of so called ‘medical-grade honey’ which is topically used for the treatment of burns, wounds and skin disorders. Nevertheless, the current set of honey quality parameters adopted in the European Union do not include its biological properties. Furthermore, in light of the accelerated growth of scientific evidence, there is an urgent need to revise current qualitative tools, and to establish and certify more effective honey quality control. Scope and approach This up-to-date narrative review aims to discuss the recent clinical evidence describing the use of honey in the management of various disorders including respiratory tract infections, metabolic and gastro-intestinal derangements. Current knowledge about the antibacterial activity of honey, as the most studied biological properties of natural honey, focusing on mechanism of action and the factors/compounds responsible for the antibacterial effects is also discussed. In addition, the weaknesses of current honey quality parameters are highlighted and a new potentially qualitative parameter that takes into account honey functionality is presented. Key findings and conclusions Data from in vitro and in vivo experiments, as well as human clinical studies clearly indicate the importance and efficacy of honey as an antibacterial agent. Antibacterial activity can vary from honey to honey but must not be identical to the activity of the honey sugar content. In most cases, antibacterial activity can be negatively impacted by thermal processing and long-term storage and this activity is therefore a suitable and sensitive quality parameter. From a clinical point of view, we strongly advocate to solely use natural honey that has undergone only minimal processing in order to preserve the full spectrum of biological activities.
... Manuka honey has a broad spectrum of antimicrobial activity and can suppress a wide range of bacterial and yeast infections. It is also effective against multidrug-resistant bacteria [19][20][21][22]. Manuka honey is sold for therapeutic purposes based on the "Unique Manuka ...
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Manuka honey originates from the New Zealand manuka tree (Leptospermum scoparium). It has been recognized for its anti-bacterial and wound-healing activity. Antibacterial activity of manuka honey is due to reactive methylglyoxal (MG) as main constituent. It is a complex mixture of carbohydrates, fatty acids, proteins, vitamins and minerals containing numerous kinds of phytochemicals with high phenolic and flavonoid content. It have also antiulcer property, cancer and skin property. Also used medicinally all over the world. Manuka honey so called unique manuka honey with the presence of methylglyoxal.
... Manuka honey has a broad spectrum of antimicrobial activity and can suppress a wide range of bacterial and yeast infections. It is also effective against multidrug-resistant bacteria [19][20][21][22]. Manuka honey is sold for therapeutic purposes based on the "Unique Manuka ...
... Other authors have found a growth inhibition of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) (Almasaudi et al. 2017, Cooper et al. 1999, Cooper et al. 2002. Moreover, the bactericidal activity of medical honey against some important resistant bacteria, such as MRSA, can be increased by the addition of a synthetic bactericidal peptide (Kwakman et al. 2011). Furthermore, some authors showed an inhibitory activity sustained by honey against Streptococcus pyogenes, Streptococcus mutans, Proteus mirabilis, P. aeruginosa, Enterococcus faecium and Enterobacter cloacae (Kwakman et al. 2008, Kwakman et al. 2010, Majtan et al. 2014. ...
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In recent years, due to the growing phenomenon of antimicrobial resistance, the search for alternative strategies to antibiotic treatments is increasing and a considerable interest for the use of medical honey in clinical practice has emerged. Honey has been used for the treatment of skin lesions, in both humans and animals. However, knowledge concerning the use of medical honey in non‑traditional companion animals is scarce. The aim of this study was to assess the antibacterial activity of a standardized medical honey (Revamil, BFactory) against bacterial strains isolated from skin lesions of non‑traditional companion animals. The minimum bactericidal concentration (MBC) of Revamil honey against seventeen clinical isolates and three reference strains was established.The medical honey showed antimicrobial activity against both Gram‑positive and Gram‑negative bacteria. Growth was inhibited for all the strains at concentrations of medical honey ranging from 10 to 40%. Pseudomonas oryzihabitans and Alcaligenes faecalis showed the lowest MBC (10%). The reference strain Staphylococcus aureus ATCC25923 showed a higher sensitivity to 20% honey compare to the corresponding clinical isolate (P = 0.001). The observed results suggest that Revamil could represent an effective therapeutic aid, useful for the reduction of antibiotic use, in case of pathological skin infections in non‑traditional companion animals.
... This is also a dressing preparation composed of natural components of TCM purely, free of any kinds of antibiotics used now in a surgical ward. Nursing homes will benefit from the less exposure to antibiotics in chronically hospitalized patients with the help of such a preparation, which would improve the rational use of antibiotic by means of the less induction to MDR in bacteria clinically [8] . Considering the significance mentioned above, we reported this case based on the efficacy of MLC (a jelly mixture with berberine) for the first time. ...
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... In 2011, Kwakman et al. found that medical-grade honey enriched with AMP has greater activity against antibiotic-resistant pathogens. This effect is also seen in RS honey, which, when combined with BP2 (bactericidal peptide 2) rapidly kills bacteria and possesses a broader spectrum of bactericidal activity than either BP2 or RS honey alone [30]. In addition to human applications, honey-based gels (e.g., Paw Manuka gel TM ) can also be used as veterinary medicines, for example, for the treatment of wounds in dogs, cats, and horses. ...
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... All types of honey, except chestnut, proved greater inhibitory activity against Gram positive bacteria. Chestnut honey had greater inhibitory activity against Gram-negative bacteria, particularly S. Enteritidis and S. Typhimurium, which is in accordance with the observations of other authors (Kwakman et al, 2011;Mandal and Mandal, 2011;Estevinho et al., 2008). ...
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... Bee venom produced by Apis mellifera is a complex mixture of biogenic amines, enzymes, and bioactive peptides (Şenel, E. 2019). Honey has powerful action against antibiotic-sensitive and -resistant bacteria (Kwakman, P. H.,et al 2011). ...
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Infections significantly complicate the care of children on hemodialysis and usually are associated with the use of a hemodialysis catheter for dialysis access. Infections of arteriovenous fistulae and arteriovenous grafts are uncommon, but many children on hemodialysis rely on a catheter, either while permanent access is being created or for long-term access. Catheter exit site infections most often occur independently of catheter-related bloodstream infections and are usually amenable to treatment with increased skin antisepsis and oral antibiotic provision. Tunnel infections can be more complicated and sometimes require surgical intervention and lead to catheter replacement. Catheter-related bloodstream infections are generally caused by skin flora and are often related to contamination of an open dialysis catheter hub during a dialysis treatment. Bacterial colonization of catheters and the development of biofilm also predispose to bloodstream infections. Broad-spectrum antibiotics such as vancomycin and ceftazidime are typically used for empiric antibiotic therapy. Antibiotic locks have been shown to reduce catheter infections and also augment cure rates. Catheter replacement or removal may be necessary, especially with infection with difficult-to-treat organisms or with persistent or recurrent infection.
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Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized. Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (eg, osmotic effects and pH) of honey also aid in its antibacterial actions. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey). This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types. (J WOCN 2002;29:295-300.)
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