Special Issue "Honey Bee Products as an Alternative or Complement to Classical Antibiotics"

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 September 2020).

Special Issue Editor

Dr. Piotr Szweda
E-Mail Website
Guest Editor
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland
Interests: bacteria and yeast drug resistance; staphylococcus aureus; candida spp.; bee products; essential oils; peptidoglycan hydrolases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For some years now, we have been witnessing with concern the arrival of the post-antibiotic era. The resistance of pathogenic bacteria and fungi to well-known antibiotics and synthetic chemotherapeutics is becoming a major global health-care challenge. Therefore, there is a great need to find novel, non-antibiotic chemotherapeutics with marked antibacterial/antifungal activity.

Bee products, including honey, propolis, royal jelly, pollen and fermented pollen, and bee bread, constitute a promising but still underestimated group of potential antimicrobial chemotherapeutics. For centuries, bee honey and propolis comprised the most important raw materials of folk medicine. They were successfully used in the treatment of a wide array of human diseases, including infections (mainly within the upper respiratory tract and chronic wounds). In contrast to many other popular traditional medicines, the achievements of modern medicine confirm the diverse therapeutic potential of bee products, which is a consequence of their chemical composition. The outcomes of several studies also confirmed synergistic interaction of propolis with classical antibiotics and synthetic chemotherapeutics. Therefore, the main subject of this Special Issue is all aspects of the possible application of bee products (and the chemical ingredients in these products) for the treatment of bacterial or fungal infections.

Dr. Piotr Szweda
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bacteria and fungi drug resistance
  • honey
  • propolis
  • royal jelly
  • pollen
  • bee bread
  • bee products
  • polyphenols

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Published Papers (14 papers)

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Editorial

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Editorial
Editorial for the Special Issue: “Honey Bee Products as an Alternative or Complement to Classical Antibiotics”
Antibiotics 2021, 10(3), 234; https://doi.org/10.3390/antibiotics10030234 - 26 Feb 2021
Viewed by 759
Abstract
Based on World Health Organization reports, the resistance of bacteria to well-known antibiotics is becoming a major global health challenge [...] Full article

Research

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Article
Bee Bread Exhibits Higher Antimicrobial Potential Compared to Bee Pollen
Antibiotics 2021, 10(2), 125; https://doi.org/10.3390/antibiotics10020125 - 28 Jan 2021
Cited by 4 | Viewed by 1212
Abstract
This study aimed at investigation of the antimicrobial potential of ethanolic extracts of bee bread (BB) and bee pollen (BP) and suspensions of these products in MHB (Mueller Hinton Broth). We covered 30 samples of BP and 19 samples of BB harvested in [...] Read more.
This study aimed at investigation of the antimicrobial potential of ethanolic extracts of bee bread (BB) and bee pollen (BP) and suspensions of these products in MHB (Mueller Hinton Broth). We covered 30 samples of BP and 19 samples of BB harvested in Polish apiaries. Slightly lower activity was observed against Gram-negative bacteria compared to Gram-positive staphylococci. BB extracts exhibited higher inhibitory potential with minimum inhibitory concentration (MIC) values in the range from 2.5 to 10% (v/v) against Staphylococcus aureus ATCC 25923 and ATCC 29213. Most active BB extracts, namely, BB6, BB11 and BB19, effectively inhibited growth of clinical isolates of S. aureus (n = 9), including MRSA (methicillin resistant Staphylococcus aureus) strains (n = 3) at concentrations ranging from 2.5 to 5.0% (v/v). Minimal bactericidal concentration (MBC) values were in the same range of concentrations; however, a shift from 2.5 to 5.0% (v/v) was observed for some products. The most active BP extracts inhibited the growth of reference strains of S. aureus at a concentration of 5% (v/v). Up to the concentration of 20% (v/v) three and seven BP extracts were not able to inhibit the growth of S. aureus ATCC 29213 and S. aureus ATCC 25923 respectively. The growth of staphylococci was also importantly inhibited in suspensions of the products in MHB. No correlation between phenolic content and antimicrobial activity was observed. Full article
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Article
Antibiofilm Activity of Heather and Manuka Honeys and Antivirulence Potential of Some of Their Constituents on the DsbA1 Enzyme of Pseudomonas aeruginosa
Antibiotics 2020, 9(12), 911; https://doi.org/10.3390/antibiotics9120911 - 15 Dec 2020
Cited by 4 | Viewed by 1246
Abstract
Heather honey was tested for its effect on the formation of biofilms by Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Salmonella Enteriditis and Acinetobacter baumanii in comparison with Manuka honey. At 0.25 mg/mL, Heather honey [...] Read more.
Heather honey was tested for its effect on the formation of biofilms by Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Salmonella Enteriditis and Acinetobacter baumanii in comparison with Manuka honey. At 0.25 mg/mL, Heather honey inhibited biofilm formation in S. aureus, A. baumanii, E. coli, S. Enteriditis and P. aeruginosa, but promoted the growth of E. faecalis and K. pneumoniae biofilms. Manuka honey inhibited biofilm formation in K. pneumoniae, E. faecalis, and S. Enteriditis, A. baumanii, E. coli and P. aeruginosa, but promoted S. aureus biofilm formation. Molecular docking with Autodock Vina was performed to calculate the predictive binding affinities and ligand efficiencies of Manuka and Heather honey constituents for PaDsbA1, the main enzyme controlling the correct folding of virulence proteins in Pseudomonas aeruginosa. A number of constituents, including benzoic acid and methylglyoxal, present in Heather and/or Manuka honey, revealed high ligand efficiencies for the target enzyme. This helps support, to some extent, the decrease in P. aeruginosa biofilm formation observed for such honeys. Full article
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Article
The Antibacterial Potential of Honeydew Honey Produced by Stingless Bee (Heterotrigona itama) against Antibiotic Resistant Bacteria
Antibiotics 2020, 9(12), 871; https://doi.org/10.3390/antibiotics9120871 - 05 Dec 2020
Cited by 8 | Viewed by 971
Abstract
Scientific studies about the antibacterial effects of honeydew honey produced by the stingless bee are very limited. In this study, the antibacterial activities of 46 blossom and honeydew honeys produced by both honey bees and stingless bees were evaluated and compared. All bacterial [...] Read more.
Scientific studies about the antibacterial effects of honeydew honey produced by the stingless bee are very limited. In this study, the antibacterial activities of 46 blossom and honeydew honeys produced by both honey bees and stingless bees were evaluated and compared. All bacterial isolates showed varying degrees of susceptibility to blossom and honeydew honeys produced by the honey bee (Apis cerana) and stingless bee (Heterotrigona itama and Geniotrigona thoracica) in agar-well diffusion. All stingless bee honeys managed to inhibit all the isolates but only four out of 23 honey bee honeys achieved that. In comparison with Staphylococcus aureus, Escherichia coli was found to be more susceptible to the antibacterial effects of honey. Bactericidal effects of stingless bee honeys on E. coli were determined with the measurement of endotoxins released due to cell lysis. Based on the outcomes, the greatest antibacterial effects were observed in honeydew honey produced by H. itama. Scanning electron microscopic images revealed the morphological alteration and destruction of E. coli due to the action of this honey. The combination of this honey with antibiotics showed synergistic inhibitory effects on E. coli clinical isolates. This study revealed that honeydew honey produced by H. itama stingless bee has promising antibacterial activity against pathogenic bacteria, including antibiotic resistant strains. Full article
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Article
Synergistic Effect of Propolis and Antibiotics on Uropathogenic Escherichia coli
Antibiotics 2020, 9(11), 739; https://doi.org/10.3390/antibiotics9110739 - 27 Oct 2020
Cited by 4 | Viewed by 989
Abstract
Urinary tract infections (UTIs) are the most common bacterial infections around the world. Uropathogenic Escherichia coli (UPEC) is among the main pathogens isolated in UTIs. The rate of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically and conduct to [...] Read more.
Urinary tract infections (UTIs) are the most common bacterial infections around the world. Uropathogenic Escherichia coli (UPEC) is among the main pathogens isolated in UTIs. The rate of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically and conduct to the difficulty to treat UTIs. Due to the rarefaction of new antibiotics molecules, new alternative strategies must be evaluated. Since many years, propolis has demonstrated an interesting antibacterial activity against E. coli. Here, we evaluated its activity added to antibiotics on a panel of UPEC with different resistance mechanisms. Minimal inhibitory concentrations (MICs) and time–kill curves of fosfomycin, ceftriaxone, ertapenem and ofloxacin, with and without propolis, were determined. Significant diminution of the MICs was observed using ceftriaxone or ofloxacin + propolis. Propolis alone had a bacteriostatic activity with time-dependent effect against UPEC. The addition of this nutraceutical improved the effect of all the antibiotics evaluated (except fosfomycin) and showed a synergistic bactericidal effect (fractional inhibitory concentrations index ≤ 0.5 and a decrease ≥ 2 log CFU/mL for the combination of propolis plus antibiotics compared with the antibiotic alone). Propolis is able to restore in vitro antibiotic susceptibility when added to antibiotics against UPEC. This study showed that propolis could enhance the efficiency of antibiotics used in UTIs and could represent an alternative solution. Full article
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Article
The Bactericidal Activity and Spore Inhibition Effect of Manuka Honey against Clostridioides Difficile
Antibiotics 2020, 9(10), 684; https://doi.org/10.3390/antibiotics9100684 - 09 Oct 2020
Cited by 4 | Viewed by 1160
Abstract
Clostridioides difficile colitis overgrowth occurs when the normal gut microbiome becomes disrupted, often due to antibiotics. Effective treatment remains elusive, due partly to the persistence of its spores in the gut. Natural substances like manuka honey offer an alternative antimicrobial mechanism of action [...] Read more.
Clostridioides difficile colitis overgrowth occurs when the normal gut microbiome becomes disrupted, often due to antibiotics. Effective treatment remains elusive, due partly to the persistence of its spores in the gut. Natural substances like manuka honey offer an alternative antimicrobial mechanism of action to conventional antibiotics. We investigated the antibiotic activity of manuka honey against 20 C. difficile isolates. The minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBC) of manuka honeys of methylglyoxal (MGO) grades 30+, 100+, 250+, and 400+ were determined based on broth microdilution. Sporicidal activity was assessed in a range of honey concentrations by enumerating total viable cell and spore counts at 0–96 h after organism inoculation. The MICs of C. difficile ranged from 4% to >30% (w/v). MIC50 for the four MGO grades were similar at 10–14%. MBC results for the majority of isolates were distributed bimodally at MBC/MIC ratios ≤4 or MBC >30%. Growth kinetics in honey showed total viable cell counts remaining >105 colony-forming units (CFU)/mL at all time points, whereas spore counts remained within 1-log of baseline (102 CFU/mL) in honey but steadily increased in the drug-free control to >105 CFU/mL by 96 h. Manuka honey demonstrated variable inhibitory and bactericidal activity against C. difficile. MGO grade had no noticeable impact on overall MIC distributions or bactericidal activity. Although manuka honey could inhibit spore proliferation, it did not eradicate spores completely. Full article
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Article
Medical-Grade Honey Kills Antibiotic-Resistant Bacteria and Prevents Amputation in Diabetics with Infected Ulcers: A Prospective Case Series
Antibiotics 2020, 9(9), 529; https://doi.org/10.3390/antibiotics9090529 - 19 Aug 2020
Cited by 11 | Viewed by 3142
Abstract
Diabetic ulcers are at risk of becoming chronic and infected, as diabetics have hampered vascular structures, limiting oxygen and nutrient supply. These wounds can lead to pain, malodor, functional problems, and amputation. The current rise in antibiotic resistance demands for complementary therapies. Medical-grade [...] Read more.
Diabetic ulcers are at risk of becoming chronic and infected, as diabetics have hampered vascular structures, limiting oxygen and nutrient supply. These wounds can lead to pain, malodor, functional problems, and amputation. The current rise in antibiotic resistance demands for complementary therapies. Medical-grade honey (MGH) forms an attractive option because of its antimicrobial and pro-healing properties. We aim to show the beneficial effects of MGH in infected diabetic ulcers. We present six patients with infected diabetic ulcers, of which some were at risk of (further) amputation. Previous treatments with antibiotics, silver and alginate dressings, surgical closure, and maggot therapy were ineffective; therefore, the treatment was switched to the application of MGH. MGH therapy typically reduced the malodor in a couple of days and controlled infection within 2–3 weeks. MGH also enhanced wound healing by promoting granulation tissue formation, angiogenesis, and re-epithelialization, by decreasing inflammatory and oxidative stress and providing nutrients. Together, wound healing was enhanced, and the patient’s quality of life improved. MGH is safe and cost-effective for treating complicated diabetic wounds with (antibiotic-resistant) infections and at risk of amputation. MGH forms a promising alternative or complementary therapy to replace antibiotics for treating locally infected wounds. Full article
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Article
Antimicrobial Activity against Paenibacillus larvae and Functional Properties of Lactiplantibacillus plantarum Strains: Potential Benefits for Honeybee Health
Antibiotics 2020, 9(8), 442; https://doi.org/10.3390/antibiotics9080442 - 24 Jul 2020
Cited by 7 | Viewed by 1371
Abstract
Paenibacillus larvae is the causative agent of American foulbrood (AFB), a severe bacterial disease that affects larvae of honeybees. The present study evaluated, in vitro, antimicrobial activity of sixty-one Lactiplantibacillus plantarum strains, against P. larvae ATCC 9545. Five strains (P8, P25, P86, P95 [...] Read more.
Paenibacillus larvae is the causative agent of American foulbrood (AFB), a severe bacterial disease that affects larvae of honeybees. The present study evaluated, in vitro, antimicrobial activity of sixty-one Lactiplantibacillus plantarum strains, against P. larvae ATCC 9545. Five strains (P8, P25, P86, P95 and P100) that showed the greatest antagonism against P. larvae ATCC 9545 were selected for further physiological and biochemical characterizations. In particular, the hydrophobicity, auto-aggregation, exopolysaccharides production, osmotic tolerance, enzymatic activity and carbohydrate assimilation patterns were evaluated. The five L. plantarum selected strains showed suitable physical and biochemical properties for their use as probiotics in the honeybee diet. The selection and availability of new selected bacteria with good functional characteristics and with antagonistic activity against P. larvae opens up interesting perspectives for new biocontrol strategies of diseases such as AFB. Full article
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Article
Brazilian Red Propolis Is as Effective as Amoxicillin in Controlling Red-Complex of Multispecies Subgingival Mature Biofilm In Vitro
Antibiotics 2020, 9(8), 432; https://doi.org/10.3390/antibiotics9080432 - 22 Jul 2020
Cited by 4 | Viewed by 848
Abstract
This study investigated the effects of Brazilian Red Propolis (BRP) extract on seven-day-old multispecies subgingival biofilms. Mixed biofilm cultures containing 31 species associated with periodontal health or disease were grown for six days on a Calgary device. Then, mature biofilms were treated for [...] Read more.
This study investigated the effects of Brazilian Red Propolis (BRP) extract on seven-day-old multispecies subgingival biofilms. Mixed biofilm cultures containing 31 species associated with periodontal health or disease were grown for six days on a Calgary device. Then, mature biofilms were treated for 24 h with BRP extract at different concentrations (200–1600 µg/mL), amoxicillin (AMOXI) at 54 µg/mL (positive control) or vehicle (negative control). Biofilm metabolic activity was determined by colorimetry, and bacterial counts/proportions were determined by DNA–DNA hybridization. Data were analyzed by Kruskal–Wallis and Dunn’s tests. Treatment with BRP at 1600, 800 and 400 μg/mL reduced biofilm metabolic activity by 56%, 56% and 57%, respectively, as compared to 65% reduction obtained with AMOXI. Mean total cell counts were significantly reduced in all test groups (~50–55%). Lower proportions of red, green and yellow complex species were observed upon treatment with BRP (400 µg/mL) and AMOXI, but only AMOXI reduced the proportions of Actinomyces species. In conclusion, BRP extract was as effective as AMOXI in killing seven-day-old multispecies biofilm pathogens and did not affect the levels of the host-compatible Actinomyces species. These data suggest that BRP may be an alternative to AMOXI as an adjunct in periodontal therapy. In vivo studies are needed to validate these results. Full article
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Article
Antagonistic Activity against Ascosphaera apis and Functional Properties of Lactobacillus kunkeei Strains
Antibiotics 2020, 9(5), 262; https://doi.org/10.3390/antibiotics9050262 - 18 May 2020
Cited by 16 | Viewed by 2156
Abstract
Lactic acid bacteria (LAB) are an important group of honeybee gut microbiota. These bacteria are involved in food digestion, stimulate the immune system, and may antagonize undesirable microorganisms in the gastrointestinal tract. Lactobacillus kunkeei is a fructophilic lactic acid bacterium (FLAB) most frequently [...] Read more.
Lactic acid bacteria (LAB) are an important group of honeybee gut microbiota. These bacteria are involved in food digestion, stimulate the immune system, and may antagonize undesirable microorganisms in the gastrointestinal tract. Lactobacillus kunkeei is a fructophilic lactic acid bacterium (FLAB) most frequently found in the gastrointestinal tracts of honeybees. Ascosphaera apis is an important pathogenic fungus of honeybee larvae; it can colonize the intestine, especially in conditions of nutritional or environmental stress that cause microbial dysbiosis. In this work, some functional properties of nine selected L. kunkeei strains were evaluated. The study focused on the antifungal activity of these strains against A. apis DSM 3116, using different matrices: cell lysate, broth culture, cell-free supernatant, and cell pellet. The cell lysate showed the highest antifungal activity. Moreover, the strains were shown to possess good cell-surface properties (hydrophobicity, auto-aggregation, and biofilm production) and a good resistance to high sugar concentrations. These L. kunkeei strains were demonstrated to be functional for use in “probiotic syrup”, useful to restore the symbiotic communities of the intestine in case of dysbiosis and to exert a prophylactic action against A. apis. Full article
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Review

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Review
Polyphenols of Honeybee Origin with Applications in Dental Medicine
Antibiotics 2020, 9(12), 856; https://doi.org/10.3390/antibiotics9120856 - 30 Nov 2020
Cited by 4 | Viewed by 943
Abstract
Honeybee products are a great source of polyphenols with recognized applications in dental medicine. Although their biological mechanisms in oral diseases are not fully understood, numerous in vitro, in vivo and clinical studies have reported promising results in the prevention and treatment of [...] Read more.
Honeybee products are a great source of polyphenols with recognized applications in dental medicine. Although their biological mechanisms in oral diseases are not fully understood, numerous in vitro, in vivo and clinical studies have reported promising results in the prevention and treatment of oral diseases. Bioactivities, such as antibacterial, antiviral, antiparasite, anticancer, anti-inflammatory and anti-oxidant properties, recommend their future study in order to develop efficient alternatives in the management of widespread oral conditions, such as dental caries and periodontitis. The most investigated mechanisms of polyphenols in oral health rely on their ability to strengthen the dental enamel, decrease the development of dental plaque formation, inhibit the progression of dental caries and development of dental pathogens and show anti-inflammatory properties. These features recommend them as useful honeybee candidates in the management of emerging oral diseases. Full article
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Review
Antimicrobial Activity of Bee-Collected Pollen and Beebread: State of the Art and Future Perspectives
Antibiotics 2020, 9(11), 811; https://doi.org/10.3390/antibiotics9110811 - 14 Nov 2020
Cited by 13 | Viewed by 1999
Abstract
Bee-collected pollen (BCP) is a well-known functional food. Honey bees process the collected pollen and store it in the hive, inside the comb cells. The processed pollen is called bee- bread or ambrosia and it is the main source of proteins, lipids, vitamins, [...] Read more.
Bee-collected pollen (BCP) is a well-known functional food. Honey bees process the collected pollen and store it in the hive, inside the comb cells. The processed pollen is called bee- bread or ambrosia and it is the main source of proteins, lipids, vitamins, macro-and micro-elements in honey bee nutrition. During storage, beebread undergoes solid state fermentation which preserves it and increases the bioavailability of nutrients. Research on beebread has been rather limited until now. In recent years, there is an increasing interest regarding the antimicrobial properties of BCP and beebread, due to emerging antimicrobial resistance by pathogens. Both BCP and beebread exhibit antimicrobial properties against diverse pathogens, like bacteria and fungi. As is the case with other bee products, lack of antimicrobial resistance might be attributed to the synergy of more than one antimicrobial compounds within BCP and beebread. Furthermore, BCP and bee bread exert targeted activity against pathogens and affect the host microbiome in a prebiotic manner. This review aims to present up to date research findings regarding these aspects as well as to discuss current challenges and future perspectives in the field. Full article
Review
Honey: Another Alternative in the Fight against Antibiotic-Resistant Bacteria?
Antibiotics 2020, 9(11), 774; https://doi.org/10.3390/antibiotics9110774 - 04 Nov 2020
Cited by 21 | Viewed by 1849
Abstract
Antibacterial resistance has become a challenging situation worldwide. The increasing emergence of multidrug-resistant pathogens stresses the need for developing alternative or complementary antimicrobial strategies, which has led the scientific community to study substances, formulas or active ingredients used before the antibiotic era. Honey [...] Read more.
Antibacterial resistance has become a challenging situation worldwide. The increasing emergence of multidrug-resistant pathogens stresses the need for developing alternative or complementary antimicrobial strategies, which has led the scientific community to study substances, formulas or active ingredients used before the antibiotic era. Honey has been traditionally used not only as a food, but also with therapeutic purposes, especially for the topical treatment of chronic-infected wounds. The intrinsic characteristics and the complex composition of honey, in which different substances with antimicrobial properties are included, make it an antimicrobial agent with multiple and different target sites in the fight against bacteria. This, together with the difficulty to develop honey-resistance, indicates that it could become an effective alternative in the treatment of antibiotic-resistant bacteria, against which honey has already shown to be effective. Despite all of these assets, honey possesses some limitations, and has to fulfill a number of requirements in order to be used for medical purposes. Full article
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Review
Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review
Antibiotics 2020, 9(11), 766; https://doi.org/10.3390/antibiotics9110766 - 31 Oct 2020
Cited by 7 | Viewed by 1599
Abstract
Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the “golden age” of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important [...] Read more.
Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the “golden age” of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections. Full article
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