Comparing Manuka and Other Medical Honeys as Adjunct to Antibiotic Therapy against Facultative Anaerobes

Sains Malaysiana 51(5)(2022): 1325-1337 http://doi.org/10.17576/jsm-2022-5105-05 

ABSTRACT The development of antibiotic resistance in pathogenic bacteria has created a push for new treatments, with honeys (especially Manuka) becoming a common focus due to their strong antimicrobial action. However, alternatives to Manuka are necessary, as its production is vulnerable. Additionally, research is lacking on how honey affect facultative anaerobic bacteria grown in anaerobic conditions and how honey and antibiotics interact in these conditions. In order to understand these interactions and find novel honey candidates, we investigated the antibacterial effects of four honeys (two Manuka, one Chilean and one ‘Santa Cruz’ honeydew honey) against Staphylococcus aureus and Pseudomonas aeruginosa grown aerobically and anaerobically in broth cultures, and how the honeys affected the action of common antibiotics against these bacteria using agar diffusion assays. We found all honeys to be highly effective at 75% honey, with no significant differences between honeys, showing that other honeys were suitable alternatives to Manuka at such high concentrations. At 20%, oxygen availability and bacterial species impacted the effectiveness of honeys as Santa Cruz honey was most effective aerobically but failed anaerobically, while Manuka honeys were effective against S. aureus but not P. aeruginosa in both conditions, and Chilean honey was ineffective against all samples. The addition of honey increased bacterial sensitivity to antibiotics in some cases, varying with aerobic conditions. The antibacterial activity of the honeys, and differences in conditions whether aerobically or anaerobically, were not correlated with pH, antioxidant capacity or total phenolic count. Since in all cases honeys were either beneficial or of no effect, these results supported the use of honey as adjunct to antibiotic therapy in scenarios such as on bandages, with honeys other than Manuka also being worth consideration.

INTRODUCTION Bacterial resistance to antibiotics is widely recognised as a major health concern, as infections with resistant strains of bacteria are more likely to result in fatality than non-resistant strains and the occurrence of bacterial infections which prove resistant to even last resort treatments is on the rise globally (World Health Organization 2020). This has created pressure to develop ways to combat bacterial growth that do not rely on antibiotics. One proposed alternative treatment is the use of honey, which has a long history of therapeutic use in ancient cultures (Zumla & Lulat 1989) and has more recently been shown to inhibit microbial growth, in part due to its low pH, high osmolarity and hydrogen peroxide activity (Bang et al. 2003). The use of honeys under compression bandages is now also highly recommended for burns victims, as honey helps sterilise the wound and demonstrates anti-inflammatory, anti-oxidative and pain-reducing effects (Zbuchea 2014). Over the last decade, research has especially highlighted the positive effects of honey produced in New Zealand from the Leptospermum scoparium brush, which is also known as Manuka honey. Manuka honey has been found to impede the growth of methicillin-resistant Staphylococcus aureus (MRSA), as well as Gramnegative bacteria, such as Pseudomonas aeruginosa and Escherichia coli (Bulman et al. 2017), while being resistant to bacterial defensive mechanisms such as biofilm formation (Lu et al. 2014). The exact mechanisms by which honeys inhibit bacterial growth seem to vary. Methylglyoxal, a compound common in Manuka honey, has been found to suppress bacterial growth by itself, though only at a 20-fold increased concentration of thatwith which it is present in Manuka honey (Bulman et al. 2017). Manuka honey has also been found to remain active when methylglyoxal has been removed, suggesting that this honey’s mode of action is multifactorial (Kwakman et al. 2011a). More generally, honeys tend to be highly acidic and contain hydrogen peroxide (H2 O2 ), both of which have been found to inhibit bacterial growth (Bang et al. 2003). Honeys also tend to have a high antioxidant capacity and total phenolic count (TPC), a higher concentration of which is generally correlated with stronger antibacterial action (Stagos et al. 2018). One little-explored aspect of research on the antibacterial effects of honey is the effect of conditions such as oxygen availability. Low oxygen and anoxic conditions are common in wounds surrounded by traumatised tissue and lead to a higher risk of infection and slower wound healing (Bowler et al. 2001). The use of honeys on these types of wounds, as well as chronic wounds such as ulcers, has been shown to increase wound healing rates with lower rates of infection than existing non-honey methods in several studies and clinical case reports (Al-Waili & Saloom 1999; Dunford & Hanano 2004; Molan 2006). These studies did not, however, examine the specific effects of oxygen conditions on the antibacterial activity of honey. As the activity of honey is attributed in large part to its antioxidant effects, oxygen conditions may have an impact on its effectiveness in lower concentrations. In particular, there is no previous research conducted on honey using facultative anaerobic bacteria, such as S. aureus and P. aeruginosa, in anaerobic conditions. There is, however, a growing body of studies interested in the use of honey as an adjuvant to antibiotic therapy.

A combination of these treatments allows broader protection, as the honey directly inhibits bacterial growth at the site where it is applied, while an antibiotic can combat any bacteria that have infiltrated into deeper tissue or the bloodstream. Hayes et al. (2018) found synergistic effects between the aforementioned methylglyoxal present in Manuka honey and the antibiotic linezolid. The researchers reported that exposure to Manuka honey was found to increase the sensitivity of S. aureus to linezolid, as the methylglyoxal increased intracellular concentrations of the antibiotic. This warrants further studies in order to determine synergistic, or antisynergistic, effects between different honeys and common antibiotics. It is also notable that so much of the current literature is focused on Manuka honey, which is reliant on a small population of a single species of plant. Should this population be suddenly affected by a new epidemic disease or if the export of this honey becomes restricted for other reasons, adapted therapies using Manuka would be impossible. It is therefore advisable to attempt to identify honeys from other sources which could serve as an alternative to Manuka honey. In summary, there is a lack of research on changes in the antibacterial effects of honey against facultative anaerobic bacteria in differing oxygen conditions, and how this affects their combination with antibiotics, all of which are important to consider in the context of topical application of honeys on bandaged wounds. Previous honey research has focused on the monofloral Manuka honey, whose production is potentially vulnerable, and thus viable alternatives should be identified.

erature by comparing the antibacterial activity of four honeys on S. aureus and P. aeruginosa in aerobic and anaerobic conditions in order to identify how oxygen availability might affect the activity of the honeys against facultative anaerobic bacteria, as well as the combined effects of honeys and common antibiotics. A branded ‘active’ floral honey from the Chilean Andes, and a honeydew honey from local pine trees from a private manufacturer in Santa Cruz (CA, USA) were compared to two Manuka honeys approved by NHS Scotland for use in clinical settings (Medihoney and Activon) in order to determine their viability as alternatives to Manuka honey. The characteristics of these honeys, including pH, sugar content, hydrogen peroxide activity, antioxidant capacity and total phenolic count, were measured in order to establish whether these measures were correlated with the antibacterial activity of these honeys.

Sains Malaysiana 51(5)(2022): 1325-1337 http://doi.org/10.17576/jsm-2022-5105-05