Karen M. Dente, MA, MD
Introduction
The recalcitrant nature and complexity of chronic wounds continue to challenge health practitioners in the field, with many of the standard treatment options often failing to provide good outcomes. Chronic wounds are often infected with bacteria resistant to antibiotics, compounding the problem. Some alternative biologic forms of treatment have been used and are gaining recognition; they include apitherapy (application of honey), maggots, and leeches. In addition to other wound-promoting actions, they all seem to show efficacy against bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA).
Honey — A Topical Treatment for Wounds
In recent years, there has been a resurgent interest in the use of honey in wound care. Honey, a plant nectar that is modified by the honey bee Apis mellifera, has been used as a treatment for wounds since antiquity, with records of its use dating back to the early Egyptians, Assyrians, Chinese, Greeks, and Romans.
There are several mechanisms through which honey is thought to act on and heal wounds. When it is applied directly on a wound surface or via a dressing, it can act as a sealant, keeping the wound moist and free from contamination. In addition, honey is comprised of glucose (35%), fructose (40%), sucrose (5%), and water (20%). This high sugar content plus vitamins, minerals, and amino acids) provides topical nutrition that is thought to promote healing and tissue growth. Honey is also a hyperosmotic agent that draws fluid from the wound bed and underlying circulation, which kills bacteria that cannot thrive in such an environment. It is bactericidal in other ways as well. During the process of honey production, worker bees add the enzyme glucose oxidase to the nectar. When honey is applied to the wound, this enzyme comes into contact with oxygen in the air, which leads to the production of the bactericide hydrogen peroxide. Macroscopically, honey has also shown debriding action.[1-3]
Manuka (Medihoney) is a medicinal honey with enhanced antibacterial properties derived from floral sources in Australia and New Zealand. In June and July 2007, Health Canada and the US Food and Drug Administration (FDA), respectively, cleared it as the first medicinal honey product for use in wounds and burns. Peter Molan, a New Zealand biochemist at the University of Waikato, has reported that it can stop bacterial growth even when diluted up to 56 times. He has conducted studies on this honey in rats and piglets that have suggested that it has anti-inflammatory properties and can stimulate epithelial growth, advancing closure of skin in these animals.[4]
"In the last few years, a lot of good science has been done in the area," said Shona Blair, a microbiologist at the University of Sydney, Australia in an interview. She has tested various strains of honeys against bacterial strains obtained from hospitals and found that even the strains most resistant to antibiotics failed to grow in the presence of honey. Manuka honey may even be active against MRSA.[5,6]
A review of the literature suggests positive results for honey in wound care, but more confirming evidence is needed. About 17 randomized controlled trials involving a total of 1965 participants have been published; 5 other types of clinical trials involving 97 participants treated with honey have also been reported in the literature. Furthermore there are about 16 trials of honey on a total of 533 wounds in animal models (which rule out a placebo effect). There are over 270 cases, of mostly chronic wounds cited in the literature that were treated with honey. Honey gave good results in all but 14 of these cases.[7,8]
For example, Dr. Jennifer Eddy, associate professor of family medicine at the University of Wisconsin, provided a case study of a patient with a severely gangrenous diabetic foot ulcer that was salvaged following honey treatment.[9] Dr. Eddy is currently recruiting patients with diabetic foot ulcers for a study that will compare honey with hydrogel dressings that appear like honey, having been altered to resemble honey in terms of coloring and smell to maintain objectivity. Not all case studies have been positive, however.
An observational study at the University of Bonn, Germany, reported good healing rates in the use of honey as a dressing for wounds in 15 children with cancer, who are prone to weakened immunity and poor wound healing following radiation treatment and chemotherapy. While more studies are needed, the results seen in children looked promising, and study author Arne Simon, MD, says specialists should consider standardized honey when confronted with wounds that refuse to heal.
Another study is underway at the Red Cross War Memorial Children's Hospital in Cape Town, South Africa, comparing a standard treatment with honey-based antibacterial wound gel product in approximately 80 children with burns.
Manuka honey has used in Iraq where it produced good results at a makeshift clinic in the treatment of children with burns set up by US armed forces.[11] Honey is an ideal affordable first aid dressing material, especially for emergent situations where standard medications and equipment are not readily available, such as war-torn or earthquake-stricken regions. It is suitable for treatment of burns, where emergency cooling with contaminated water can lead to infection.
Maggot Therapy
Maggots have been used for centuries to help heal wounds, especially by military surgeons who noted that soldiers whose wounds became infested with maggots healed better. The beneficial effects of therapeutic maggots were first observed during the Napoleonic war by a surgeon who noted that soldiers whose wounds had become infested had an improved prognosis.[12] When novel surgical techniques and antibiotics were discovered during WWII, maggot debridement therapy (MDT) moved into the background.[13]
Medicinal maggots (sterilized larvae of the green bottle fly Lucilia sericata that do not reproduce nor feed on live tissue) work as biochemical debriding agents. They ingest bacteria and degrade them in their intestinal tract. They also secrete an enzyme that disinfects the wound, dissolves necrotic tissue, and stimulates wound healing. Maggots are now being used against a wide spectrum of wounds and are proving to be effective against MRSA and other multiresistant microorganisms. They also appear to be more cost effective than other methods of wound healing.[12,14,15]
"Studies indicate that about 40% to 50% of wounds treated with maggot therapy as the last alternative before amputation were healed, and the limbs were saved," according to Dr. Ronald Sherman, a pathologist at UC Irvine who has been breeding and studying maggots for years. The practice has been growing by about 25% a year in the United States according to him.[16,17]
Maggots received marketing clearance as "medical devices" by the FDA in January 2004, making them the first live organism marketed in the United States. Therapy is currently reimbursable by Medicare.
About 50 centers in North America, 400 in the United Kingdom, more than 140 in Germany, and more worldwide currently offer maggot therapy as an option for treatment in wound care.[18]
Leeches in Wound Healing
The leech, once an indispensable part of the practice of medicine in the 19th century only to be abandoned in favor of scientific medical advances, is seeing a renaissance in the area of modern plastic reconstructive surgery — particularly in microsurgery transplantation.
In the United States, medicinal leeches (Hirudo medicinalis) were cleared as a medical device in June 2004 by the FDA (shortly after maggots received clearance) and are used today throughout the world as tools in skin grafts and reattachment microsurgery.
The renewed interest in leeches can be ascribed to 2 Slovenian surgeons who described their use to prevent venous congestion of skin-flap transplants in an article in the British Journal of Plastic Surgery in 1960.[19] Leeches work by creating a puncture wound that bleeds for hours, while anesthetizing the wound, preventing clotting and dilating vessels to increase blood flow.
Then in 1985, Joseph Upton, a Harvard plastic surgeon, used leeches in the reattachment of an ear in a small child. Ears have been notoriously difficult to transplant successfully due to the clotting of minute blood vessels during the procedure. The use of leeches saved the boy's ear.[20]
The medical literature describes countless cases of the use of leeches to relieve venous congestions following reattachment or transplantation surgery of fingers, toes, ears, penis, and other skin-flaps; in addition to breast reconstruction, reduction, or augmentation procedures where engorgement of the nipple can be a complication.[21,22]
Leeches possess properties that make them uniquely able to assist with venous compromised tissues. Their saliva contains:
* Hirudin, a direct thrombin inhibitor;
* Hyaluronidase, which increases the local spread of leech saliva through human tissue at the site of the wound and also has antibiotic properties;
* A histamine-like vasodilator that promotes local bleeding; and
* A local anesthetic.
Aeromonas hydrophila infections are a recognized complication of postoperative leech application, with reported incidences ranging from 2.4% to 20%. Prophylactic antibiotics are often recommended. In the event infection develops, early diagnosis and immediate initiation of an empirical intravenous antibiotic therapy are essential.[23-25] Another major concern in the use of leeches is their migration from the surgical site, possibly into the body or the wound itself. One study suggested a possible simple solution, which was to attach 1 end of a surgical suture to the leech and tie the free end to a firm object or dressing.[26]
While leeches still aren't a surgeon's first choice, they are considered in a transplant that has failed for lack of venous outflow on the patient that has been put on heparin or other anticoagulants, and has undergone repeat surgeries in which as many of the small veins have been attempted to be connected. Randomized-controlled trials are pending to elucidate the benefit of H medicinalis in accordance with evidence-based criteria.[27]
References
1. Lusby PE, Coombes A, Wilkinson JM. Honey: a potent agent for wound healing. J Wound Ostomy Continence Nurs. 2002;29:295-300. Abstract
2. Fox C. Honey as a dressing for chronic wounds in adults. Br J Commun Nurs. 2002;7:530-534.
3. Ahmed AK, Hoekstra MJ, Hage JJ, Karim RB. Honey-medicated dressing: transformation of an ancient remedy into modern therapy. Ann Plast Surg. 2003;50:143-147; discussion 147-148.
4. Molan PC, Clinical usage of honey as a wound dressing: an update. J Wound Care. 2004;13:353-356. Abstract
5. Natarajan S, Williamson D, Grey J, Harding KG, Cooper RA. Healing of an MRSA-colonized, hydroxyurea-induced leg ulcer with honey. J Dermatol Treat. 2001;12:33-36.
6. Cooper RA, Molan PC, Harding KG. Antibacterial activity of honey against strains of Staphylococcus aureus from infected wounds. J R Soc Med. 1999;92:283-285. Abstract
7. Molan PC. The evidence supporting the use of honey as a wound dressing. Int J Low Extrem Wounds. 2006;5:40-54. Abstract
8. Moore OA, Smith LA, Campbell F, Seers K, McQuay HJ, Moore RA. Systematic review of the use of honey as a wound dressing. BMC Complement Altern Med. 2001;1:2.
9. Eddy JJ, Gideonsen MD. Observations from practice. Topical honey for diabetic foot ulcers. J Fam Pract. 2005;54:533-535. Abstract
10. Kingsley A. The use of honey in the treatment of infected wounds: case studies. Br J Nurs. 2001;10:S13-S16, S18, S20. Abstract
11. Dente, K. Cheap Fix in a War Zone. Los Angeles Times, September 10, 2007. Available at: http://www.latimes.com/features/health/medicine/la-he-labside10sep10,1,511904.story?coll=la-health-medicine Accessed October 24, 2007.
12. Parnés A, Lagan KM. Larval therapy in wound management: a review. Int J Clin Pract. 2007;61:488-493. Abstract
13. Sherman RA, Sherman J, Gilead L, Lipo M, Mumcuoglu KY. Maggot debridement therapy in outpatients. Arch Phys Med Rehabil. 2001;82:1226-1229. Abstract
14. Sherman RA, Wyle F, Vulpe M. Maggot debridement therapy for treating pressure ulcers in spinal cord injury patients. J Spinal Cord Med. 1995;18:71-74. Abstract
15. Bexfield A, Nigam Y, Thomas S, Ratcliffe NA. Detection and partial characterisation of two antibacterial factors from the excretions/secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA). Microbes Infect. 2004;6:1297-1304. Abstract
16. Sherman RA, Hall MJR, Thomas S. Medicinal maggots: An ancient remedy for some contemporary afflictions. Annu Rev Entomol. 2000;45:55-81. Abstract
17. Dente K. Maggot Therapy: Gross? Sure — But Better Than Losing a Leg. Los Angeles Times, September 10, 2007. Available at: http://www.latimes.com/features/health/medicine/la-he-labbox10sep10,1,7464464.story?coll=la-health-medicine Accessed October 24, 2007.
18. Grassberger M, Fleischmann W. The biobag — A new device for the application of medicinal maggots. Dermatology. 2002;204:306.
19. Derganc M, Zdravic F. Venous congestion of flaps treated by application of leeches. Br J Plast Surg. 1960;13:187-192. Abstract
20. Banis JC, Upton J. Microsurgical reattachment of totally amputated ears. Plast Reconstr Surg. 1987;79:535-541. Abstract
21. Knobloch K et al. Hirudo medicinalis-leech application in plastic and reconstructive microsurgery — a literature review. Handchir Mikroochir Plast Chir. 2007;39:103-107.
22. Conforti ML, Connor NP, Heisey DM, Hartig GK. Evaluation of performance characteristics of the medicinal leech for the treatment of venous congestion. Plast Reconstr Surg. 2002;109:228-235. Abstract
23. Bauters TG, Buyle FM, Verschraegen G, et al. Infection risk related to the use of medicinal leeches. Pharm World Sci. 2007;29:122-125. Abstract
24. Kalbermatten DF, Rieger UM, Uike K, Erba P, Laifer G, Hintermann B. [Infection with Aeromonas hydrophila after use of leeches (Hirudo medicinalis) in a free microvascular osteo-(myo-)cutaneous flap — suggestions for successful management] Handchir Mikrochir Plast Chir. 2007;39:108-111.
25. Lineaweaver WC, Hill MK, Buncke GM, et al. Aeromonas hydrophila infections following use of medicinal leeches in replantation and flap surgery. Ann Plast Surg. 1992;29:238-244. Abstract
26. Granzow JW, Armstrong MB, Panthaki ZJ. A simple method for the control of medicinal leeches. J Reconstr Microsurg. 2004;20:461-462. Abstract
27. Utley DS, Koch RJ, Goode RL. The failing flap in facial plastic and reconstructive surgery: role of the medicinal leech. Laryngoscope. 1998;108:1129-1135. Abstract
