MAGGOT DEBRIDEMENT THERAPY

MAGGOT DEBRIDEMENT THERAPY




The green bottle fly Lucilia sericata

The beneficial effect of fly larvae for wounds was first observed by Ambroise Pare, in the 16th Century. Baron Larrey, physician-in-chief to Napoleon's armies and Dr. Joseph Jones, a medical officer during the American Civil war, while working with soldiers who remained wounded for several days in the battle fields, described that maggots destroy only dead tissue, and do not injure living tissue.

Maggot debridement therapy (MDT), the treatment of suppurative skin infections with the larvae of calliphorid flies, was first introduced by Baer in 1931. This method was used extensively in the 1930's and early 1940's in over 300 hospitals in the USA alone, and was abandoned later with the introduction of antibiotics and the use of aggressive surgical debridement. Since then maggots were used only occasionally as salvage therapy for skin and soft tissue wounds which did not respond to surgery and antibiotic therapy. Since 1989 in the USA and since mid 1990's in Great Britain Germany, Sweden, Switzerland and Israel MDT has been re-introduced for the treatment of intractable wounds. During the last 15 years jover 20,000 patients have been treated by this method.

a. Clinical work

Since 1996 our team treated over 600 chronic wounds in ca. 400 patients, aged 32-95 (median 67). The underlying disease was mainly diabetes (50%) and venous stasis (20.5%), however patients with paraplegia, hemiplegia, vascular disease, Birger's disease, lymphostasis, thalassemia, polycytemia, dementia and basal-cell carcinoma were also treated. The wounds had been present for 1-200 months (median: 5, average 10.5) before MDT was applied. Most of the wounds were sloughy and necrotic and were located on the foot or the thigh, while the 35 pressure sores were located on the lower back. Three patients with carcinoma or sarcoma on the hand were also treated by maggot therapy. The patients were treated either ambulatory or hospitalized in different Departments of Hadassah Hospital (e.g., Dermatology, Orthopedics, Vascular Surgery and Internal Medicine (Diabetes and Day Care Units), as well as in Sharei Zedek Hospital, Kupat Holim Klalit Hospital, three geriatric hospitals (Neve Horim, Vayizrah Yitzchak, French Hospital and Hod Yerushalayim) and one outpatient clinic (Kiriat Menachem) in Jerusalem. In addition, patients hospitalized in Tel Hashomer (Tel-Aviv, Zamenhoff (Tel-Aviv), Assaf Harofe (Tschrifin), Woffson (Holon), Ramban (Haifa), Emek (Afula) and Meir Hospital (Kfar Sava) were also treated. Maggot therapy was selected because all the other surgical and non-surgical treatment methods such as hydrogel dressings, antibiotics, hyperbaric oxygen and disinfectants, had failed to cure the wounds.

Sterile maggots (24-48 hrs old) of the green bottle fly, Lucilia sericata were administered to the wound 2-5 times weekly and replaced every 1-2 days. Depending on the size of the wound the number of treatments varied between 1 and 48 (median: 4, average 4.6), and lasted for a period of 1-45 days (median: 6, average: 8.6).

Complete debridement was achieved in 79.5% of the wounds, significant debridement in 16.9%, partial debridement in 2.4% and in only 1.2% of the cases the wound remained unchanged. In at least 40 cases an imminent leg amputation was prevented as a result of maggot therapy. As the therapy progressed, new layers of healthy tissue were formed over the wounds, while the offensive odor emanating from the necrotic tissue and the intense pain accompanying the wound decreased significantly. The majority of the patients did not complain about any major discomfort during the treatment.

It was observed that maggots are capable of entering any part of the wound wherever necrotic tissue exists and clean minute areas without harming healthy tissue in a manner resembling micro-surgery; a task which is very difficult to attain by the conventional surgery. After MDT, patients were sent either for a skin transplant or their wounds were treated with hydrocolloidal sheets or disinfectants.

Maggot therapy is a rapid and effective treatment alternative, indicated for large necrotic wounds requiring debridement when conventional treatment and conservative surgical intervention do not help (A 60, A 64, A 69, A 76, A77, A 92, A 101, A 106, A 110).

b. Antibacterial substances from maggots

Green fluorescent protein-producing Escherichia coli were used to investigate the fate of bacteria in the alimentary tract of sterile grown maggots using a laser scanning confocal microscope. A computer program was applied to analyze the intensity of the fluorescence and to quantify the number of bacteria. The crop and the anterior midgut were the most heavily infected areas of the intestine. A significant decrease in the amount of bacteria was observed in the posterior midgut. The number of bacteria decreased even more significantly in the anterior hindgut and practically no bacteria were seen in the posterior end, near the anus. The viability of bacteria in the different gut sections was examined. It was shown that 66.7% of the crops, 52.8% of the midguts, 55.6% of the anterior hindguts and 17.8% of posterior hindguts harbored living bacteria. In conclusion, during their passage through the digestive tract the majority of E. coli was destroyed in the midgut. Most of the remaining bacteria were killed in the hindgut, indicating that the feces were either sterile or contained only small numbers of bacteria (A 72).

Low molecular weight molecules were isolated by HPLC from the maggot or hemolymph extracts of Lucilia sericata. Using GC-MS analysis, three compounds were obtained: p-hydroxybenzoic acid (PHBA, MW 138), p-hydroxyphenylacetic acid (PHPAA , MW 152) and octahydro-dipyrrolo[1,2-a;1',2'-d] pyrazine-5,10-dione (MW 194), also known as the cyclic dimer of proline [or proline diketopiperazine or cyclo(Pro,Pro)]. All three molecules revealed antibacterial activity when tested against Micrococcus luteus and/or Pseudomonas aeruginosa, while the effect was even more pronounced when these molecules were tested in combination and caused lysis of these bacteria (A 105).

Sterile and non-sterile maggots maintained in the laboratory and taken from wounds of treated patients were used. Whole body extracts and haemolymph was fractionated and their range of activity against bacteria was tested by the zone inhibition assay. The mode of action of bacterial destruction was examined by viable counts, influx of K+, changes in the membrane potential by scanning electron microscope (SEM). Extracts of sterile and non-sterile maggots showed an activity of 200 arbitrary units (AU)/ml and 400AU/ml respectively. Maggots removed from chronic wounds had an activity of 1200AU/ml. Injuring sterile maggots with a sterile needle doubled the antibacterial activity within 24 hours, while the antibacterial activity of haemolymph increased fourfold after injuring with a sterile needle and 16-fold with an infected needle. The fractions with a molecular weight of <1kDa and 3–10kDa showed antibacterial activity against Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa, Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) isolated from wounds. The fraction with a MW <1kDa lysed over 90% of the bacteria within 15 minutes by causing an influx of K+ and changing the membrane potential of bacteria (A 104).

Maggots of the green blowfly, Lucilia sericata were used as an alternative to surgical intervention and long-term antiseptic therapy for the treatment of chronic wounds. The secretions of maggots are known to have antibacterial properties. To quantify the bactericidal effect of secretions from larvae of L. sericata, an in-vitro test model based on the modified European quantitative suspension test (EN 1040) was developed, in which a co-culture of maggots and bacteria (Micrococcus luteus, Escherichia coli, Methicillin-sensitive Staphylococcus aureus) in tryptic soy broth was tested. The numbers of bacterial colonies with and without maggot exposure were compared after 24, 48, and 72 h of exposure. The mean log10 reduction factor (RF) for bacterial elimination per maggot was > 4 at all examined times for all tested bacteria. Thus, maggot secretion fulfilled the required definitions of an antiseptic. In addition, maggot’s ability of ingesting bacteria was also evaluated. Maggots contained viable bacteria after 48 h of contact with the respective organisms. These maggots also continued excreting bacteria. Therefore maggots should be disposed after use as they must be regarded as medical waste (A 103).

d. Case report

The patient, a 75-year-old male, had been suffering from lymphostasis for about 50 years, and was hospitalized in a clinic for the chronically ill in Jerusalem. Two months earlier, after receiving a small injury, the patient developed sepsis and renal failure, and gangrene developed on his left leg below the knee. Serological tests indicated that he was infected with a strain of Streptococcus A. After surgical debridement and disinfection three times daily, the wound became heavily infected (Fig. 1). The patient suffered intense pain and it was impossible to transplant skin onto the leg at this stage and amputation of the leg was recommended.

Approximately 1,000 maggots, 48 hrs old, were placed on the wound daily for 5 days a week, and left for 24 hrs before being replaced by new larvae. The maggots cleaned the entire infected area and healthy granulation appeared after two weeks of treatment (Fig. 2). Meanwhile the pain diminished significantly. Thereafter the patient was referred for autologous skin transplantation.

            Figure 1. Before treatment                                 Figure 2: After treatment
leg treated


Publications

A 60. Mumcuoglu, K.Y., M. Lipo, I. Ioffe-Uspensky, J. Miller, I. Turkeltaub & R. Galun. 1997. Maggot therapy for the treatment of gangrene and osteomyelitis. Harefuah 132: 323-325.

A 64. Mumcuoglu, K.Y., A. Ingber, L. Gilead, J. Stessman, R. Friedman, H. Schulman, H. Bichucher, I. Ioffe-Uspensky, J. Miller, R. Galun & I. Raz. 1998. Maggot therapy for the treatment of diabetic foot ulcers. Diabetes Care, 21: 2030-2031.

A 69. Mumcuoglu, K.Y., A. Ingber, L. Gilead, J. Stessman, R. Friedmann, H. Schulman, H. Bichucher, I. Ioffe-Uspensky, J. Miller, R. Galun & I. Raz. 1999. Maggot therapy for the treatment of intractable wounds. Intnl. J. Dermatol. 8: 623-627.

A 72. Mumcuoglu, K.Y., J. Miller, M. Mumcuoglu, M. Friger & M. Tarshis. 2001. Destruction of bacteria in the digestive tract of the maggot of Lucilia sericata (Diptera: Calliphoridae). J. Med. Entomol. 38: 161-166.

A 76. Mumcuoglu, K.Y. 2001. Clinical applications for maggots in wound care. Am. J. Clin. Dermatol. 2: 219-227.

A 77. Sherman, R. A., J. M-T Sherman, L. Gilead, M. Lipo & K.Y. Mumcuoglu. 2001. Maggot debridement therapy in outpatients. Arch. Phys. Med. Rehabil. 82: 1226-1229.

A 92. Tanyuksel, M., E. Araz, K. Dundar, G. Uzun, T. Gumus, B. Alten, F. Saylam, A. Taylan-Ozkan & K.Y. Mumcuoglu. 2005. Maggot debridement therapy in the treatment of chronic wounds in a military hospital setup in Turkey. Dermatology 210: 115-118.

A 101. Mumcuoglu, K.Y. & L. Gilead. 2006. Clinical use of maggots for the treatment of wounds (in Hebrew). Aurora 32-34.

A 103. Daeschlein, G., K.Y. Mumcuoglu, O. Assadian, B. Hoffmeister & A. Kramer. 2007. In vitro antibacterial activity of Lucilia sericata maggot secretions. Skin Pharmacol. Physiol. 20:112–115 (DOI: 10.1159/000097983).

A 104. Huberman, L., N. Gollop, K.Y. Mumcuoglu, C. Blockc & R. Galun. 2007. Antibacterial properties of the whole body extracts and hemolymph of Lucilia sericata maggots. J. Wound Care 16: 123-127.

A 105. Huberman, L., N. Gollop, K.Y. Mumcuoglu, E. Breuer, S.R. Bhusare, Y. Shai & R. Galun. 2007. Antibacterial substances of low molecular weight isolated from Lucilia sericata (Diptera: Muscidae). Med. Vet. Entomol. 21: 127-131.

A 106. Brin, Y.S., K.Y. Mumcuoglu, S. Massarwe, M. Wigelman, E. Gross & M. Nyska. 2007. Chronic foot ulcer management using maggot debridement and topical negative pressure therapy. J. Wound Care 16:111-113.

A 110. Taylan-Ozkan, A. & K.Y. Mumcuoglu. 2007. Maggot debridement therapy for the treatment of a venous stasis ulcer (in Turkish). Turkish Bull. Hyg. Exp. Biol. 64: 31-34.