Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review

Victoria C Nolan, James Harrison, John E E Wright, Jonathan A G Cox, Victoria C Nolan, James Harrison, John E E Wright, Jonathan A G Cox

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 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.

Keywords: Manuka honey; antibiotic resistance; honey; medical-grade honey.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MICs of the S. aureus isolates tested against a variety of Manuka and medical-grade honeys. (A) All the Manuka honey MIC data used in this review, identifying Manuka honey and Comvita Manuka honey UMF5+ as the most effective; and (B) all the medical-grade honey MIC data used in this review, identifying all three Surgihoneys as the most effective.
Figure 2
Figure 2
MICs of the P. aeruginosa isolates tested against a variety of Manuka and medical-grade honey. (A) All the Manuka honey MIC data used in this review, identifying the ungraded Manuka honey and Comvita Manuka UMF5+ as the most effective; and (B) all the medical-grade honey MIC data used in this review, identifying the three Surgihoneys as the most effective.
Figure 3
Figure 3
MICs of the E. coli isolates tested against a variety of Manuka and medical-grade honey. (A) All the Manuka honey MIC data used in this review, identifying an ungraded Manuka honey and Manuka honey UMF16+ as the most effective; and (B) all the medical-grade honey MIC data used in this review, identifying the three Surgihoneys as the most effective.
Figure 4
Figure 4
MICs of the K. pneumoniae isolates tested against a variety of Manuka and medical-grade honey. (A) The Manuka honey MIC data used in this review, identifying a similar response in MIC for all isolates; and (B) the medical-grade honey MIC data used in this review, identifying the three Surgihoneys as the most effective.
Figure 5
Figure 5
MICs of all other Staphylococcus isolates tested against a variety of Manuka and medical-grade honey. (A) All the Manuka honey MIC data used in this review, identifying the Comvita Manuka 5+ as the most effective honey; (B) all the medical-grade honey MIC data used in this review, identifying the Comvita Manuka Woundcare 18+ as the most effective.
Figure 6
Figure 6
MICs of all other enteric bacterial isolates tested against a variety of Manuka and medical-grade honey. (A) All the Manuka honey MIC data used in this review, identifying the Manuka honey UMF16+ as the most effective; and (B) the medical-grade honey MIC data used in this review, identifying a similar activity between the Revamil and Activon medical-grade honeys.
Figure 7
Figure 7
MICs of all other isolates tested against a variety of Manuka and medical-grade honey. (A) All the Manuka honey MIC data used in this review, identifying the ungraded Manuka honey and Manuka honey UMF16+ as the most effective; and (B) all the medical-grade honey MIC data used in this review, identifying a range of effectiveness between the honeys.
Figure 8
Figure 8
PRISMA diagram showing how records were screened and selected to be used for the systematic review.

References

    1. Samarghandian S., Farkhondeh T., Samini F. Honey and health: A review of recent clinical research. Pharmacogn. Res. 2017;9:121–127. doi: 10.4103/0974-8490.204647.
    1. Eteraf-Oskouei T., Najafi M. Traditional and modern uses of natural honey in human diseases: A review. Iran. J. Basic Med. Sci. 2013;16:731–742. doi: 10.22038/ijbms.2013.988.
    1. Bucekova M., Jardekova L., Juricova V., Bugarova V., Di Marco G., Gismondi A., Leonardi D., Farkasovska J., Godocikova J., Laho M., et al. Antibacertial Activity of Different Blossom Honeys: New Findings. Molecules. 2019;24:1573. doi: 10.3390/molecules24081573.
    1. Mandal M.D., Mandal S. Honey: Its medicinal property and antibacterial activity. Asian Pac. J. Trop. Biomed. 2011;1:154–160. doi: 10.1016/S2221-1691(11)60016-6.
    1. Nolan V.C., Harrison J., Cox J.A.G. Dissecting the antimicrobial composition of honey. Antibiotics. 2019;8:251. doi: 10.3390/antibiotics8040251.
    1. Albaridi N.A. Antibacterial Potency of Honey. Int. J. Microbiol. 2019;2019:1–10. doi: 10.1155/2019/2464507.
    1. Chirife J., Zamora M.C., Motto A. The correlation between water activity and % moisture in honey: Fundamental aspects and application to Argentine honeys. J. Food Eng. 2006;72:287–292. doi: 10.1016/j.jfoodeng.2004.12.009.
    1. El Sohaimy S.A., Masry S.H.D., Shehata M.G. Physicochemical characteristics of honey from different origins. Ann. Agric. Sci. 2015;60:279–287. doi: 10.1016/j.aoas.2015.10.015.
    1. Brudzynski K. Effect of hydrogen peroxide on antibacterial activities of Canadian honeys. Can. J. Microbiol. 2006;52:1228–1237. doi: 10.1139/w06-086.
    1. John-isa J.F., Adebolu T.T., Oyetayo V.O. Antibacterial Effects of Honey in Nigeria on Selected Diarrhoeagenic Bacteria. South Asian J. Res. Microbiol. 2019;3:1–11. doi: 10.9734/sajrm/2019/v3i230083.
    1. Alvarez-suarez J.M., Tulipani S., Díaz D., Estevez Y., Romandini S., Giampieri F., Damiani E., Astolfi P., Bompadre S., Battino M. Antioxidant and antimicrobial capacity of several monofloral Cuban honeys and their correlation with color, polyphenol content and other chemical compounds. Food Chem. Toxicol. 2010;48:2490–2499. doi: 10.1016/j.fct.2010.06.021.
    1. Isla M.I., Craig A., Ordoñez R., Zampini C., Sayago J., Bedascarrasbure E., Alvarez A., Salomón V., Maldonado L. Physico chemical and bioactive properties of honeys from Northwestern Argentina. LWT Food Sci. Technol. 2011;44:1922–1930. doi: 10.1016/j.lwt.2011.04.003.
    1. Fyfe L., Okoro P., Paterson E., Coyle S., Mcdougall G.J. Compositional analysis of Scottish honeys with antimicrobial activity against antibiotic-resistant bacteria reveals novel antimicrobial components. LWT Food Sci. Technol. 2017 doi: 10.1016/j.lwt.2017.01.023.
    1. Escuredo O., Silva L.R., Valentão P., Seijo M.C., Andrade P.B. Assessing Rubus honey value: Pollen and phenolic compounds content and antibacterial capacity. Food Chem. 2012;130:671–678. doi: 10.1016/j.foodchem.2011.07.107.
    1. Matzen R.D., Leth-Espensen J.Z., Jansson T., Nielsen D.S., Lund M.N., Matzen S. The Antibacterial Effect in Vitro of Honey Derived from Various Danish Flora. Dermatol. Res. Pract. 2018;2018:1–10. doi: 10.1155/2018/7021713.
    1. Deng J., Liu R., Lu Q., Hao P., Xu A., Zhang J., Tan J. Biochemical properties, antibacterial and cellular antioxidant activities of buckwheat honey in comparison to manuka honey. Food Chem. 2018;252:243–249. doi: 10.1016/j.foodchem.2018.01.115.
    1. Hegazi A.G. Antimicrobial Activity of Different Egyptian H.pdf. Res. J. Microbiol. 2011;6:488–495.
    1. Laallam H., Boughediri L., Bissati S., Menasria T., Mouzaoui M.S., Hadjadj S., Hammoudi R., Chenchouni H. Modeling the synergistic antibacterial effects of honey characteristics of different botanical origins from the Sahara Desert of Algeria. Front. Microbiol. 2015;6:1–12. doi: 10.3389/fmicb.2015.01239.
    1. Johnston M., Mcbride M., Dahiya D., Owusu-apenten R. Antibacterial activity of Manuka honey and its components: An overview. AIMS Microbiol. 2018;4:655–664. doi: 10.3934/microbiol.2018.4.655.
    1. Cokcetin N.N., Pappalardo M., Campbell L.T., Brooks P., Carter D.A., Blair S.E., Harry E.J. The antibacterial activity of Australian Leptospermum honey correlates with methylglyoxal levels. PLoS ONE. 2016;11:1–13. doi: 10.1371/journal.pone.0167780.
    1. Adams C.J., Manley-Harris M., Molan P.C. The origin of methylglyoxal in New Zealand manuka (Leptospermum scoparium) honey. Carbohydr. Res. 2009;344:1050–1053. doi: 10.1016/j.carres.2009.03.020.
    1. Grainger M.N.C., Manley-harris M., Lane J.R., Field R.J. Kinetics of the conversion of dihydroxyacetone to methylglyoxal in New Zealand mā nuka honey: Part II–Model systems. Food Chem. 2016;202:492–499. doi: 10.1016/j.foodchem.2016.02.030.
    1. Molan P.C., Betts J.A. Clinical usage of honey as a wound dressing: An update. J. Wound Care. 2004;13:353–356. doi: 10.12968/jowc.2004.13.9.26708.
    1. Lu J., Carter D.A., Turnbull L., Rosendale D., Hedderley D., Stephens J., Gannabathula S., Steinhorn G., Schlothauer R.C., Whitchurch C.B., et al. The Effect of New Zealand Kanuka, Manuka and Clover Honeys on Bacterial Growth Dynamics and Cellular Morphology Varies According to the Species. PLoS ONE. 2013;8:e55898. doi: 10.1371/journal.pone.0055898.
    1. Jubeh B., Breijyeh Z., Karaman R. Resistance of gram-positive bacteria to current antibacterial agents and overcoming approaches. Molecules. 2020;25:2888. doi: 10.3390/molecules25122888.
    1. O’Neil J. Review on Antibiotic resisitance. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. Heal. Wealth Nations. 2014:1–16. doi: 10.1787/5jxvl3dwk3f0-en.
    1. Datta R., Juthani-Mehta M. Burden and management of multidrug-resistant organisms in palliative care. Palliat. Care. 2017;10:10. doi: 10.1177/1178224217749233.
    1. Dunford C., Cooper R., Molan P., White R. The use of honey in wound treatment. Nurs. Stand. 2000;15:63–68. doi: 10.7748/ns2000.11.15.11.63.c2952.
    1. Mashhood A.A., Khan T.A., Sami A.N. Honey compared with 1% silver sulfadiazine cream in the treatment of superficial and partial thickness burns. J. Pak. Assoc. Dermatol. 2006;16:14–19.
    1. Subrahmanyam M. Honey Dressing Accelerates Split-Thickness Skin Graft Donor Site Healing. Indian J. Surg. 2015;77:261–263. doi: 10.1007/s12262-012-0789-9.
    1. Girma A., Seo W., She R.C. Antibacterial activity of varying UMF-graded Manuka honeys. PLoS ONE. 2019;14:e0224495. doi: 10.1371/journal.pone.0224495.
    1. Tan H.T., Rahman R.A., Gan S.H., Halim A.S., Hassan S.A., Sulaiman S.A., Singh K.-K.B. The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey. BMC Complement. Altern. Med. 2009;9:34. doi: 10.1186/1472-6882-9-34.
    1. Willix D.J., Molan P.C., Harfoot C.G. A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey. J. Appl. Bacteriol. 1992;73:388–394. doi: 10.1111/j.1365-2672.1992.tb04993.x.
    1. Henriques A.F., Jenkins R.E., Burton N.F., Cooper R.A. The effect of manuka honey on the structure of Pseudomonas aeruginosa. Eur. J. Clin. Microbiol. Infect. Dis. 2011;30:167–171. doi: 10.1007/s10096-010-1065-1.
    1. Sherlock O., Dolan A., Athman R., Power A., Gethin G., Cowman S., Humphreys H. Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. BMC Complement. Altern. Med. 2010;10:47. doi: 10.1186/1472-6882-10-47.
    1. Lin S.M., Molan P.C., Cursons R.T. The controlled in vitro susceptibility of gastrointestinal pathogens to the antibacterial effect of manuka honey. Eur. J. Clin. Microbiol. Infect. Dis. 2011;30:569–574. doi: 10.1007/s10096-010-1121-x.
    1. Cremers N., Belas A., Santos Costa S., Couto I., de Rooster H., Pomba C. In vitro antimicrobial efficacy of two medical grade honey formulations against common high-risk meticillin-resistant staphylococci and Pseudomonas spp. pathogens. Vet. Dermatol. 2020;31:90–96. doi: 10.1111/vde.12811.
    1. Kwakman P.H.S., Van den Akker J.P.C., Güçlü A., Aslami H., Binnekade J.M., de Boer L., Boszhard L., Paulus F., Middelhoek P., te Velde A.A., et al. Medical-Grade Honey Kills Antibiotic-Resistant Bacteria In Vitro and Eradicates Skin Colonization. Clin. Infect. Dis. 2008;46:1677–1682. doi: 10.1086/587892.
    1. Dryden M., Lockyer G., Saeed K., Cooke J. Engineered honey: In vitro antimicrobial activity of a novel topical wound care treatment. J. Glob. Antimicrob. Resist. 2014;2:168–172. doi: 10.1016/j.jgar.2014.03.006.
    1. Tirado D.J., Hudson N.R., Maldonado C.J. Efficacy of medical grade honey against multidrug-resistant organisms of operational significance: Part i. J. Trauma Acute Care Surg. 2014;77:204–207. doi: 10.1097/TA.0000000000000324.
    1. Jenkins R., Cooper R. Improving Antibiotic Activity against Wound Pathogens with Manuka Honey In Vitro. PLoS ONE. 2012;7:e45600. doi: 10.1371/journal.pone.0045600.
    1. Cooper R.A., Jenkins L., Henriques A.F.M., Duggan R.S., Burton N.F. Absence of bacterial resistance to medical-grade manuka honey. Eur. J. Clin. Microbiol. Infect. Dis. 2010;29:1237–1241. doi: 10.1007/s10096-010-0992-1.
    1. Hammond E.N., Donkor E.S. Antibacterial effect of Manuka honey on Clostridium difficile. BMC Res. Notes. 2013;6:188. doi: 10.1186/1756-0500-6-188.
    1. Roberts A.E.L., Maddocks S.E., Cooper R.A. Manuka honey is bactericidal against Pseudomonas aeruginosa and results in differential expression of oprF and algD. Microbiology. 2012;158:3005–3013. doi: 10.1099/mic.0.062794-0.
    1. Sindi A., Chawn M.V.B., Hernandez M.E., Green K., Islam M.K., Locher C., Hammer K. Anti-biofilm effects and characterisation of the hydrogen peroxide activity of a range of Western Australian honeys compared to Manuka and multifloral honeys. Sci. Rep. 2019;9:1–17. doi: 10.1038/s41598-019-54217-8.
    1. Glasser J.S., Guymon C.H., Mende K., Wolf S.E., Hospenthal D.R., Murray C.K. Activity of topical antimicrobial agents against multidrug-resistant bacteria recovered from burn patients. Burns. 2010;36:1172–1184. doi: 10.1016/j.burns.2010.05.013.
    1. Carter D.A., Blair S.E., Cokcetin N.N., Bouzo D., Brooks P., Schothauer R., Harry E.J. Therapeutic manuka honey: No longer so alternative. Front. Microbiol. 2016;7:1–11. doi: 10.3389/fmicb.2016.00569.
    1. Cooke J., Dryden M., Patton T., Brennan J., Barrett J. The antimicrobial activity of prototype modified honeys that generate reactive oxygen species (ROS) hydrogen peroxide. BMC Res. Notes. 2015;8:4–8. doi: 10.1186/s13104-014-0960-4.
    1. Mohd Zohdi R., Abu Bakar Zakaria Z., Yusof N., Mohamed Mustapha N., Abdullah M.N.H. Gelam (Melaleuca spp.) honey-based hydrogel as burn wound dressing. Evidence-Based Complement. Altern. Med. 2012;2012:1–7. doi: 10.1155/2012/843025.
    1. Jull A.B., Cullum N., Dumville J.C., Westby M.J., Deshpande S., Walker N. Honey as a topical treatment for wounds (Review) Cochrane Libr. 2015;6:CD005083. doi: 10.1002/14651858.CD005083.pub4.
    1. Molan P.C. Re-introducing honey in the management of wounds and ulcers-theory and practice. Ostomy Wound Manage. 2002;48:28–40.
    1. Molan P.C. The evidence supporting the use of honey as a wound dressing. Int. J. Low. Extrem. Wounds. 2006;5:40–54. doi: 10.1177/1534734605286014.
    1. Rabie E., Serem J.C., Oberholzer H.M., Gaspar A.R.M., Bester M.J. How methylgyloxal kills bacteria: An ultrastructural study. Ultrastruct. Pathol. 2016;40:107–111. doi: 10.3109/01913123.2016.1154914.
    1. Henriques A.F., Jenkins R.E., Burton N.F., Cooper R.A. The intracellular effects of manuka honey on Staphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis. 2010;29:45–50. doi: 10.1007/s10096-009-0817-2.
    1. Saranraj P., Sivasakthi S. Comprehensive Review on Honey: Biochemical and Medicinal Properties. J. Acad. Ind. Res. 2018;6:165–181.
    1. Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 2003;3:710–720. doi: 10.1038/nri1180.
    1. Brudzynski K., Abubaker K., Miotto D. Unraveling a mechanism of honey antibacterial action: Polyphenol/H2O2-induced oxidative effect on bacterial cell growth and on DNA degradation. Food Chem. 2012;133:329–336. doi: 10.1016/j.foodchem.2012.01.035.
    1. McLoone P., Warnock M., Fyfe L. Honey: A realistic antimicrobial for disorders of the skin. J. Microbiol. Immunol. Infect. 2016;49:161–167. doi: 10.1016/j.jmii.2015.01.009.
    1. Almasaudi S.B., Al-Nahari A.A.M., Abd El-Ghany E.S.M., Barbour E., Al Muhayawi S.M., Al-Jaouni S., Azhar E., Qari M., Qari Y.A., Harakeh S. Antimicrobial effect of different types of honey on Staphylococcus aureus. Saudi J. Biol. Sci. 2017;24:1255–1261. doi: 10.1016/j.sjbs.2016.08.007.
    1. Kwakman P.H.S., Velde A.A., Boer L., Speijer D., Vandenbrouke-Grauls C.M.J.E., Zaat S.A.J. How honey kills bacteria. FASEB J. 2010;24:2576–2582. doi: 10.1096/fj.09-150789.
    1. Halstead F.D., Webber M.A., Oppenheim B.A. Use of an engineered honey to eradicate preformed biofilms of important wound pathogens: An in vitro study. J. Wound Care. 2017;26:442–450. doi: 10.12968/jowc.2017.26.8.442.
    1. NHS . Medical Honey Simplified. A Patient Guide to the Role of Honey in Wound Management. NHS; Oxford, UK: 2015.
    1. Landis S., Ryan S., Woo K. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals. HMP Communications; Malver, PA, USA: 2007. Infections in chronic wounds.
    1. Cefalu J.E., Barrier K.M., Davis A.H. Wound Infections in Critical Care. Crit. Care Nurs. Clin. N. Am. 2017;29:81–96. doi: 10.1016/j.cnc.2016.09.009.
    1. Sen C.K. Human Wounds and Its Burden: An Updated Compendium of Estimates. Adv. Wound Care. 2019;8:39–48. doi: 10.1089/wound.2019.0946.
    1. Malic S., Hill K.E., Hayes A., Percival S.L., Thomas D.W., Williams D.W. Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescent in situ hybridization (PNA FISH) Microbiology. 2009;155:2603–2611. doi: 10.1099/mic.0.028712-0.
    1. Edwards R., Harding K.G. Bacteria and wound healing. Curr. Opin. Infect. Dis. 2004;17:91–96. doi: 10.1097/00001432-200404000-00004.
    1. Ranall M.V., Butler M.S., Blaskovich M.A.T., Cooper M.A. Resolving Biofilm Infections: Current Therapy and Drug Discovery Strategies. Curr. Drug Targets. 2012;13:1375–1385. doi: 10.2174/138945012803530251.
    1. Lu J., Turnbull L., Burke C.M., Liu M., Carter D.A., Schlothauer R.C., Whitchurch C.B., Harry E.J. Manuka-type honeys can eradicate biofilms produced by Staphylococcus aureus strains with different biofilm-forming abilities. PeerJ. 2014;2014:1–25. doi: 10.7717/peerj.326.
    1. Subrahmanyam M. A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine. Burns. 1998;24:157–161. doi: 10.1016/S0305-4179(97)00113-7.
    1. Kingsley A. The use of honey in the treatment of infected wounds: Case studies. Br. J. Nurs. 2001;10:S13–S20. doi: 10.12968/bjon.2001.10.Sup5.12323.
    1. AL-Waili N., Al Ghamdi A., Ansari M.J., Al-Attal Y., Al-Mubarak A., Salom K. Differences in composition of honey samples and their impact on the antimicrobial activities against drug multiresistant bacteria and pathogenic fungi. Arch. Med. Res. 2013;44:307–316. doi: 10.1016/j.arcmed.2013.04.009.
    1. European Centre for Disease Prevention and Control The bacterial challenge: Time to react. ECDA/EMEA Jt. Tech. Rep. 2009
    1. Rhomberg P.R., Fritsche T.R., Sader H.S., Jones R.N. Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA) Diagn. Microbiol. Infect. Dis. 2006;56:57–62. doi: 10.1016/j.diagmicrobio.2005.12.009.
    1. Samtani M.N., Flamm R., Kaniga K., Nandy P. Pharmacokinetic-pharmacodynamic-model-guided doripenem dosing in critically ill patients. Antimicrob. Agents Chemother. 2010;54:2360–2364. doi: 10.1128/AAC.01843-09.
    1. Theuretzbacher U. Pharmacokinetic and pharmacodynamic issues for antimicrobial therapy in patients with cancer. Clin. Infect. Dis. 2012;54:1785–1792. doi: 10.1093/cid/cis210.
    1. Jenkins R.E., Cooper R. Synergy between oxacillin and manuka honey Sensitizes methicillin-resistant Staphylococcus aureus to oxacillin. J. Antimicrob. Chemother. 2012;67:1405–1407. doi: 10.1093/jac/dks071.
    1. Müller P., Alber D.G., Turnbull L., Schlothauer R.C., Carter D.A., Whitchurch C.B., Harry E.J. Synergism between Medihoney and Rifampicin against Methicillin-Resistant Staphylococcus aureus (MRSA) PLoS ONE. 2013;8:e57679. doi: 10.1371/journal.pone.0057679.
    1. Liu M.Y., Cokcetin N.N., Lu J., Turnbull L., Carter D.A., Whitchurch C.B., Harry E.J. Rifampicin-manuka honey combinations are superior to other antibiotic-manuka honey combinations in eradicating Staphylococcus aureus biofilms. Front. Microbiol. 2018;8:1–12. doi: 10.3389/fmicb.2017.02653.
    1. NICE . Chronic Wounds: Advanced Wound Dressings and Antimicrobial Dressings. NICE; London, UK: 2016.
    1. NICE . Diabetic Foot Problems: Prevention and Management. NICE; London, UK: 2019.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren