Clinical research on the bio‐debridement effect of maggot therapy for treatment of chronically infected lesions

Abstract

Objective:  To evaluate the bio‐debridement effect of maggot therapy for treating chronically infected lesions.

Methods:  A retrospective study was conducted of 25 patients with diabetic foot ulcers and 18 patients with pressure ulcers after spinal cord injury treated by maggot therapy or traditional dressing. Changes in the lesions were observed and bacterial cultures tested.

Results:  All ulcers healed completely. The times taken to achieve bacterial negativity, granulation and healing of lesions were all significantly shorter in the maggot therapy group than in the control group, both for diabetic foot ulcers (P < 0.05) and pressure ulcers (P < 0.05).

Conclusion:  Maggot therapy is a safe and effective method for treating chronically infected lesions.

Introduction

Chronically infected lesions are clinically common and troublesome to treat, especially in aged patients with systemic diseases such as diabetes mellitus and paraplegia. They make a significant impact on the health care system because of the long‐term care required and the associated cost. The therapeutic utilization of maggot for wound healing dates back to the beginning of civilization. This kind of therapy became popular and was often used around the world for chronic or infected lesions during the 1930s ¹ . With the introduction and production of antibiotics in the 1940s however, academic and clinical interest was unfortunately lost. In the 1990s the rising incidence of antibiotic resistance resulted in a renaissance of maggot therapy. Despite repeatedly falling out of favor and the persistent public disdain which hampers its acceptance, the practice of maggot therapy is on the rise around the world on account of its efficacy, safety and simplicity ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ . Recently, Sherman and Mumcuoglu 12, 13, 14, 15, 16. The present study was designed to evaluate the bio‐debridement effects of maggots in patients suffering from diabetic ulcers and pressure ulcers after spinal cord injury, by using larvae of the green‐bottle fly Lucilia sericata ² , ¹¹ .

Materials and methods

Patient data

From January 2005 to June 2008, a consecutive series of patients with infected diabetic foot ulcers or pressure ulcers after spinal cord injury were treated in our hospital. Before treatment, all the lesions were evaluated by four experienced orthopedic surgeons to make sure they could be treated with either maggot therapy or a traditional dressing method. Patients who were agreeable to maggot therapy received it, and were accordingly allocated to the study group. Patients who were not agreeable to maggot therapy were treated by a traditional dressing method, and were accordingly allocated to the control group. Patient information is presented in Table 1. After treatment, the times taken to achieve bacterial negativity, granulation and wound healing were documented, analyzed and compared. Patients with the following were excluded: symptoms of systemic infection, positive blood bacterial cultures, and gangrene in the area of the local lesion. The study was approved by the Ethics Committee of Dalian Medical University for carrying out research on human subjects. The patients who were agreeable to maggot therapy were required to sign an informed consent form.

Table 1.

Patient information

Group	Sex		Age (years) Mean ± 1SD (range)	Wound area (cm2) Mean ± 1SD (range)	Infective bacteria (number of cases)
	Male	Female			Staphylococcus aureus	Pseudomonas aeruginosa
Diabetic foot ulcers
Control group	7	5	52.7 ± 4.1 (46–60)	16.9 ± 3.9 (10–24)	12	0
Study group	10	3	54.1 ± 3.7 (48–60)	17.8 ± 4.3 (12–26)	13	0
Pressure ulcers
Control group	5	3	47.4 ± 4.9 (34–53)	27.6 ± 5.2 (7–42)	5	3
Study group	7	3	48.4 ± 5.1 (32–55)	28.3 ± 5.5 (9–45)	7	3

Preparation of maggots

Firstly, eggs were collected from the eyes of Scomberomorus niphonius and disinfected in 1% sodium sulfite solution for 3 min, and subsequently in 3% Lysol brand disinfectant for 5 min. The disinfected eggs were then transferred to sterile vials to clone. Secondly, third stage larvae of Lucilia sericata were selected to be placed in 3.5% formalin for 5 min, 2% hydrogen peroxide solution for 3 min, and then 5% dilute hydrochloric acid solution for 5 min. After the two‐step disinfection, the larvae remined vigorous. A hundred randomly selected larvae were proven to be aseptic by bacterial culture test.

Treatment

After two‐step disinfection, disinfected larvae were applied to the lesion. In cases where the lesion was dry, gauze soaked in hypertonic saline was placed on it in order to keep it moist to accomodate the larvae's preferences. The skin around the lesion was covered with sterile saline gauze with a hole cut in the middle to match its dimensions. The larvae were placed on the lesion through the hole at a density of five to ten per cm² and the number of larvae delivered was recorded. Then a disinfected nylon cage which was slightly larger than the gauze and lesion was fixed to the skin surrounding the wound by medical adhesive. Finally the cage was lightly covered with a gauze wrap to absorb the draining exudates without obstructing the flow of air.

Every day the dressing and larvae were changed, the lesions checked and the condition of the lesions and the number of larvae documented (Fig. 1). This procedure continued until the lesions had healed. In the control group, a dressing was applied daily with normal saline only and, if necessary, surgical debridement was performed. The exudates from the lesions in the two groups were cultured every time.

Figure 1.

Maggots used to treat wounds. (A) Before treatment, the number of larvae delivered was recorded; (B) The body of maggot before treatment was about 1.5 cm long.

Other ancillary measures for ulcers were the same for the two groups. No systemic antibiotics were used for the duration of treatment. In the diabetic foot ulcer patients, blood glucose was controlled to normal values with subcutaneous insulin. In the pressure ulcer patients, a soft pad was inserted between the patient's back and the bed to make a local depression.

Statistical analysis

All the presented data were expressed as mean ± SD, and their statistical significance analyzed by the independent sample t‐test using SPSS 12.0 software. A P‐value of less than 0.05 was considered to be statistically significant.

Results

In the maggot therapy group, there were no major complications except that one patient complained of bearable pain. After a cycle, the larvae were two to three times larger than when they were introduced and, because they did not remain in the deep tissue of the patients, the number of larvae was consistent before and after the treatment.

Patients suffering from diabetic foot ulcers

All the diabetic foot ulcers healed completely. The time taken to achieve bacterial negativity, granulation and wound healing in the maggot therapy group was significantly shorter than in the control group (P < 0.05, Table 2). All patients were followed up for 3.5 to 6 months (mean 4 months), and none of the ulcers recurred.

Table 2.

Healing process of diabetic foot ulcers

Groups	Time to granulation (days) Mean ± 1SD	Time to bacterial negativity (days) Mean ± 1SD	Time to healing of lesion (days) Mean ± 1SD
Control group	6.3 ± 1.2	16.1 ± 3.8	39.6 ± 13.4
Study group	3.1 ± 1.2	12.0 ± 2.5	26.4 ± 12.6
t‐value	6.67	3.20	2.17
P value	0.000	0.004	0.042

Patients suffering from pressure ulcers after spinal cord injury

All the pressure ulcers healed completely. The time taken to achieve bacterial negativity, granulation and wound healing in the maggot therapy group was significantly shorter than in the control group (P < 0.05, Table 3). All patients were followed up for 2 to 6 months (mean 3.5 months), and none of the ulcers not recurred.

Table 3.

Healing process of pressure ulcers after spinal cord injury

Groups	Time to granulation (days) Mean ± 1SD	Time to bacterial negativity (days) Mean ± 1SD	Time to wound healing (days) Mean ± 1SD
Control group	4.8 ± 1.0	13.1 ± 2.2	30.6 ± 12.2
Study group	2.5 ± 1.0	10.4 ± 1.8	18.7 ± 10.4
t‐value	4.89	2.57	2.24
P value	0.000	0.022	0.039

Case report

A woman with type 2 diabetes mellitus underwent removal of the left first and second toes because of ineffective conservative treatment. Her blood glucose was well controlled. However, 12 months after surgery, the incision became necrotic and infected (Fig. 2A). The surface area of the ulcer was about 3.5 cm × 5 cm and the pathogenic bacterium was Staphylococcus aureus. Maggot therapy was initiated at a density of ten per cm² after the patient gave permission for it when the ulcer failed to respond to therapy with conventional dressing and antibiotics. Four days after application, fresh tissue had begun to grow and production of pus had visibly reduced (Fig. 2B); by 16 days after application, the pus had disappeared and abundant fresh tissue was apparent (Fig. 2C); by 55 days after application the infected lesion had healed completely (Fig. 2D). The ulcer did not recur within the 2 months of follow up.

Figure 2.

Diabetic foot ulcer treated with maggot therapy. (A) Before maggot therapy, much purulent and necrotic tissue is visible. (B) 4 days after maggot therapy, fresh tissue has grown and pus secretion is reduced visibly. (C) 16 days after maggot therapy, pus secretion has disappeared and abundant fresh tissue is apparent. (D) 55 days after maggot therapy the infected wound has healed completely.

Discussion

Effect of maggot therapy

Sherman et al. believe that maggot therapy is more effective and efficient at debriding chronic pressure ulcers than are conventional treatments¹². Courtenay et al. 3, 4, 10. In the present study, vigorous maggots were applied to the surface of the infected lesions, and the exudation from the lesions was regularly tested by bacterial culture. As a consequence of this treatment, the results gradually changed from positive to negative. Our results demonstrate that maggots employ several mechanisms to to produceinhibit antibiotic‐resistant bacteria in notoriously difficult‐to‐treat wounds ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , which is consistent with the studies conducted by Sherman¹² and Courtenay^3,4,10.

Mechanisms of maggot therapy

The mechanisms of maggot therapy are mainly associated with debridement, disinfection and the consequent enhancement of wound healing. Thomas et al. 23, 24, 25. This is known as bio‐debridement or maggot debridement therapy: the maggots can be considered as street sweepers. The maggots move around the lesion using their mouth hooks to facilitate debridement. Furthermore, the maggots also secrete some proteolytic enzymes which effectively degrade components of the extracellular matrix (ECM), including laminin and fibronectin ²⁶ . In the present study, the amount of necrotic tissue and purulent secretion gradually reduced as fresh granulation appeared, and the size of the maggots after a cycle of treatment was two to three times larger than that when they were delivered, indicating that maggots naturally choose necrotic tissue and bacterial debris as their favorite food and their weight increases accordingly.

Currently, two kinds of antibacterial peptides have been identified in the excretions/secretions (ES) of medicinal maggots, suggesting that the ES contribute to their inhibitory effect on Gram‐positive and Gram‐negative bacteria, including methicillin‐sensitive Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa ²⁷ . Bonn reported that maggots can kill or inhibit the growth of a range of pathogenic bacteria, especially Staphylococcus aureus and Group A and B Streptococci, and that they also show some activity against Pseudomonas species ²⁸ . All these reports indicate that maggots are capable of disinfecting wounds.

Horobin et al. reported that the mechanisms by which maggots enhance wound healing may be via the promotion of fibroblast motility, acceleration of ECM remodeling and coordination of cellular responses²⁹. In the present study, all the ulcers in the study group healed earlier than those of the control group, which again proves that maggots can facilitate the healing of infected wounds.

Preparation of larvae

Third stage larvae were chosen for therapeutic maggots as suggested by Courtenay and Sherman ³ , ¹⁶ , because this stage is relatively long and the larvae have a good appetite for necrotic tissue in order to turn into pupae. It should be noted that after debriding necrotic tissue, the larvae would have to look for dry soil to turn into pupae, thus they will not stay in healthy tissue.

In the present study two‐step disinfection, which can easily be adopted by doctors, was applied. Firstly the eggs were disinfected and then the third stage larvae were disinfected just before application. The chemical solutions used to disinfect were effective without destroying the vitality of the maggots, so that the maggots were not only aseptic but also vigorous.

Indications and complications

Clinical indications for maggot therapy vary but, in particular, they are: (i) chronic wounds infected with multi‐drug‐resistant bacteria which are unresponsive to traditional treatment and (ii) presence of significant co‐morbidities precluding surgical intervention. Maggot therapy may not be the first choice for all kinds of wounds, but surgeons should keep the method in mind.

Mild adverse reactions, including pain, pyrexia, influenza‐like symptoms and escape of larvae are infrequent ³ , as are severe adverse effects—five bloodstream infections attributed to contaminated larvae have been reported ³⁰ . All cases participating in the present study had no major adverse effects or complications, except one patient complained of bearable pain which disappeared after treatment with analgesics. In order to avoid such complications, doctors should use disinfected larvae, intensive nursing and psychological preparation of patients.

In a word, maggot therapy is a safe and effective method for chronically infected wounds. However, prospective, randomized and controlled trials are required in China to establish acceptable criteria for clinical outcomes and guidelines for best practice. In addition, more work should be undertaken on the molecular mechanisms of maggots or the influence of maggots' secretions on the cells involved in wound healing, which may even include apoptosis of such cells, in order to make delivery of larvae easy and maggot therapy more acceptable and efficient.

Disclosure

The authors declare that there are no competing interests in this research.