Antimicrobial Stewardship With Honey

Exploring the antimicrobial properties of honey for wounds and synovial structures.
Horse with medicinal manuka honey
Several reports support using honey not only for treating skin wounds and infections but also for preventing and treating infections in synovial structures. | Arnd Bronkhorst Photography

Honey is more than a fancily packaged bee creation sold by apiarists at local farmers markets on Saturday mornings. This golden elixir has many medicinal qualities that are as relevant today as they were in ancient times when honey was a major medical product. Indeed, paintings from the Stone Age 8,000 years ago show people treating disease with bee products such as honey. Scrolls and tablets from the Egyptians and other ancient cultures dating back to 6200 B.C. show honey being widely used as a drug. Honey, according to Samarghandian et al. (2017), is the oldest known wound-healing agent. 

Honey apparently fell out of favor with the advent of antimicrobials (penicillin) in 1928 by Alexander Fleming. In light of the recent rampant development and spread of antimicrobial resistance, however, many medical experts are revisiting nonmedical approaches, including good old-fashioned honey. 

“We all should be concerned about antibiotic resistance. Systemic and topical antibiotics are generally overused and inappropriately used without culture and sensitivity in the treatment of open wounds in horses,” says Andrew Dart, BVSc, PhD, Dipl. ACVS, emeritus professor and director of the research and clinical training unit at University of Sydney, in Australia.

Dart, who has been researching and using manuka honey for more than 15 years, notes that in addition to being an effective surgical debridement and lavage to avoid needing antibiotics, “honey, particularly manuka honey, can be used as an alternative topical antimicrobial agent without the risk of antimicrobial resistance.”

Several recently published scientific reports support using honey not only for treating skin wounds and infections but also for preventing and treating infections in synovial structures. Before delving into the results of those clinical trials, let’s first look at the demonstrated and hypothesized mechanisms of action and safety of nonmedical and medical manuka honey formulations.  

Honey’s Mechanisms of Action

More than 300 types of honey reportedly exist, differing based on the nectar collected by honeybees. In addition to fructose and glucose, honey contains proteins, vitamins, minerals, and organic acids, as well as flavonoids (e.g., phytoestrogens), polyphenols, anthraquinone, and volatile compounds. An estimated 180 chemical substances are believed to exist in honey (Albaridi 2019). 

Researchers have confirmed honey has several antimicrobial effects, starting with simple dehydration. 

“The high sugar content produces an osmotic gradient that leads to bacterial dehydration and disruption of the cell wall,” Dart explains. “The osmotic gradient also promotes an influx of fluid, lymph, and nutrients into the wound and enhances autolytic wound debridement and supports healing.” 

Next, hydrogen peroxide activity contributes to honey’s antimicrobial properties. 

“Worker bees produce glucose oxidase that oxidizes glucose into gluconic acid, thereby releasing hydrogen peroxide,” says Dart. “Hydrogen peroxide exhibits antimicrobial properties against most forms of microorganisms, including dormant forms with known high resistance profiles, such as bacterial spores and protozoal cysts. It acts as a strong oxidative biocide to generate free radical species to induce DNA, protein, and membrane lipid damage through oxidation.”

Finally, Greiner (2022) reports the acidic pH itself deters the growth of microorganisms and honey might affect bacteria by changing their cell structure, decreasing membrane potential, disrupting the cell cycle and metabolism, and affecting efflux pump mechanisms. 

Study results show honey inhibits both Gram-positive and Gram-negative bacteria through both bactericidal and bacteriostatic mechanisms. Carnwath et al. (2014) conducted a study assessing the antimicrobial activity of 11 honeys against pathogens isolated from equine wounds. Those pathogens included methicillin-resistant Staphylococcus aureus and Pseudomonas.  

“Eight products were effective against all 10 bacterial isolates at concentrations varying from < 2% to 16% v/v,” concluded the research team. 

This study included commercial medical grade honeys, supermarket honeys, and honeys from local beekeepers. 

Manuka vs. Generic Honey

Manuka Honey
Manuka honey is a natural topical product with no side effects that potentially reduces or removes the need for antimicrobial use. | Getty Images

“All honeys have some generic properties that can potentially benefit wound healing,” says Dart. “As wounds or infection become more serious, then these generic properties are likely to be overwhelmed.” 

This is where manuka honey comes into play. 

Manuka honey is a specific type of honey produced by bees foraging manuka plants native to Australia and New Zealand. According to Carnwath et al., manuka honey might have superior antimicrobial properties because of the non-peroxidase antimicrobial activity of methylglyoxal (MGO), which is derived from dihydroxyacetone in the manuka flower’s nectar. 

“MGO is responsible for most of the antimicrobial activity of manuka honey, not hydrogen peroxide,” says Dart. “In fact, MGO has recently been shown to limit the production of hydrogen peroxide in manuka honey by inhibiting the enzyme glucose oxidase. This means that hydrogen peroxide does not contribute significantly to the antimicrobial activity of manuka honey.” 

Although its precise mode of action is not known, MGO is believed to interact with macromolecules such as DNA and RNA, says Dart. According to Combarros-Fueres et al. (2020), MGO disrupts bacterial fimbriae, flagellum, and other structures. Dart says manuka honey also inhibits the formation of biofilms and even causes detachment of established biofilms (Maddocks et al. 2012; Jervis-Bardy J et al. 2011). 

The term “Unique Manuka Factor,” or UMF, is a trademarked grading system placed on the label of commercially available manuka honey, sourced by licensed producers in New Zealand. 

“The UMF rating assures the purity and quality of the product,” says Dart. “It represents a zone of growth inhibition in a radial diffusion assay with Staphylococcus aureus when compared with a known concentration of a phenol solution.” 

Within this system, each individual batch of manuka honey gets tested for antimicrobial activity. For a batch to be considered therapeutically useful, it must receive a rating of 10-15. A UMF of 16-30 indicates superior activity with high antimicrobial efficacy. 

“If manuka honey is bought from a trademarked company, it is guaranteed to have been tested and graded on its antibacterial activity. Further, some manuka products are backed by peer-reviewed literature,” Dart says. 

Manuka honey is a natural product with no side effects, a topical that potentially reduces or removes the need for topical or systemic antimicrobial use, and not associated with any concerns surrounding antimicrobial resistance.  

Considering manuka honey is expensive, some veterinarians use inexpensive commercially available honeys intended for human consumption. Carnwath et al., however, found 18 out of 29 honeys were contaminated with aerobic bacteria or fungi. Botulism is another concern associated with honeys that are not gamma-irradiated.  

“Further, standard bulk-supplied brand supermarket honeys will have been processed/ filtered/heat treated and are unlikely to have any beneficial properties,” Dart says.

Addressing the cost issue, “Wounds left to heal by second intention are expensive to treat,” he says. “Higher UMF manuka honeys are expensive, but in the overall treatment of a wound, especially if complications develop, the honey is only a small proportion of the cost.” 

Dart does warn practitioners that using manuka honey does not replace good initial wound management involving appropriate cleaning and debridement. 

“The honey should be employed early on and used as described, using only what is required to coat the wound. You don’t need large dollops … more is not necessarily better,” he says. 

Medical Uses of Honey in Equine Practice

Treating Skin Wounds and Fighting Infections 

Horse wound being treated with manuka honey
Honey should be employed early on and used as described, using only what is required to coat the wound. | Arnd Bronkhorst Photography

Wound dehiscence occurs commonly on the lower limb, primarily due to excessive tension and/or infection. Regional limb perfusion to deliver antibiotics locally can help prevent infection, ergo dehiscence, as can applying antimicrobials directly to the wound. 

“Honey has broad antibacterial activity, even against multidrug-resistant pathogens like methicillin-resistant Staphylococcus aureus, and can prevent and/or irradicate biofilm. Honey also has anti-inflammatory effects and provides the wound with nutrients to help healing,” explains Gal Kelmer, DVM, Dipl. ACVS, from the Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agricultural, Food & Environment, The Hebrew University of Jerusalem, Israel. 

Previous study results show complete healing only occurs in 21-37% of cases for wounds located on lower limbs. 

In their 2020 study, Kelmer et al. applied medical-grade honey to the subcutaneous tissues in wounds surgically managed by primary closure. The study included 127 horses: 69 treated with honey and 58 used as controls, treated using standard techniques (i.e., thorough cleaning with chlorhexidine, lavage, debridement, systemic antimicrobials, and anti-inflammatory drugs).

Of the 127 lacerations, only 53 (41.7%) healed completely. But complete healing occurred more frequently in the honey group than the control (50.7% vs. 31%, respectively). Further, more of the honey wounds were free of infection (82.6%) compared with the control group (64.9%). Finally, veterinary satisfaction with case outcome was higher in the honey group (85.4%) than the control group (67.2%). 

“Thus, intralesional application of medical-grade honey improved wound healing,” says Kelmer. “Locally applying antimicrobial substances has advantages over systemically administered antibiotics, such as decreased costs and avoiding side effects. 

“This is a simple, innovative way of markedly improving healing of lacerations and paves the way for additional blinded controlled clinical trials,” he adds. His team also did not observe any adverse effects of honey.

Preventing Incisional Infections

Following colic surgery, approximately 2.7-39% of horses develop incisional infections. Intra-incisional antibiotics have been used to decrease infection risk. With the increasing concerns regarding antimicrobial resistance, alternative means of infection prevention are warranted. With honey’s natural antimicrobial properties, Kelmer et al. were interested in exploring medical-grade honey for preventing incisional infections.

Their randomized controlled clinical trial involved 89 horses undergoing colic surgery. All horses received the hospital’s standard antimicrobial treatments, which included intravenous sodium penicillin G and gentamicin as well as a topical application of gentamicin and sodium penicillin G applied to the linea alba after closing. Honey was applied directly to the linea alba in 49 horses (1 mL per 2 cm of incision length). The subcutaneous tissues and skin were then routinely closed. 

Only 17 horses (19%) were diagnosed with incisional infections postoperatively. Only four were diagnosed prior to discharge, leaving most (76%) diagnosed by the primary veterinarian. The honey group had only four infections, which was significantly lower than the treatment group (8.2% vs. 32.5%, respectively). 

“Applying honey to the linea alba intraoperatively is a simple and rapid procedure with a strong protective effect against incisional infections,” says Kelmer. “According to the calculated absolute risk reduction, 24% of treated horses were spared from incisional infections when medical grade honey was applied to the linea .”  

Again, his team noted no adverse reactions to the honey. 

Is honey currently recommended in a clinical situation? Yes, says Kelmer, adding, “I definitely recommend it and have used it in most surgeries over the past several years with good clinical results.”

Intra-Synovial Administration 

Janine Terschuur, DVM, MRCVS, a surgeon from Cotts Equine Hospital in the United Kingdom, extended the application of medical-grade honey from the skin to synovial structures. Terschuur and colleagues applied honey to two cases of joint sepsis and one septic tendon sheath and published those results in a case series in the Canadian Journal of Veterinary Research (2023). All three equids were treated using standard surgical and medical techniques such as systemic antibiotics, lavage, and curettage. At the end of the procedure, Terschuur’s team instilled 5-10 mL of manuka honey within the synovial structure (e.g., via an egress cannula at the completion of endoscopic surgery). In two of the three cases, honey was administered with 200 mg amikacin.    

All three cases recovered well and remained free of lameness during the follow-up period. 

If interested in attempting this procedure, Terschuur and colleagues recommended warming the honey to dissolve the sugar crystals prior to injecting. 

Terschuur says additional studies are warranted to compare honey’s efficacy to that of antibiotics and to explore honey’s biocompatibility with articular cartilage. 

Take-Home Message

Honey offers an exciting option as a natural antibiotic, a feature that becomes increasingly important in the face of growing antimicrobial resistance. 

“The healing of distal limb wounds in horses is often problematic, protracted, and expensive,” says Dart. “A veterinarian’s role is to assist and direct the natural processes that lead to effective healing.”

He says overtreatment or excessive intervention can derail the process. The only phase of healing in which a veterinarian can make a significant impact is the debridement phase. Effective debridement of dead, necrotic, and contaminated tissues will improve the rate and quality of healing. It allows for early development of a healthy granulation bed and the early removal of bandages. Bandaging has been shown to slow healing in distal limb wounds in horses and promote the production of excessive granulation tissue, which delays contraction and interferes with the healing process. 

“Indiscriminate use of systemic and topical antibiotics should be avoided unless they are directly indicated and backed up with deep wound culture and antibiotic sensitivity,” Dart says. “A topical, natural product like generic honey that has not been processed for supermarket sale or, better still, manuka honey with a manufacturer-labeled UMF factor provides an established alternative as a topical agent. There is no risk of antimicrobial resistance, it can be used under a bandage or on the open wound, it is a natural product that owners often prefer, and it comforts and engages the owner in the treatment process.” 

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