Maggot therapy for resistant infections: the disconnect between scientific evidence, clinical acceptance and practice.

OBJECTIVE: Practitioners and scientists are re-examining marginalised wound care therapies to find strategies that combat the growing problem of antimicrobial resistance (AMR) without compromising patient outcomes. Maggot therapy (MT) makes up just an estimated 0.02% of UK's National Health Service spending on wound care. This study aims to uncover why MT is not used more often, despite its affordability and high level of efficacy for both debridement and disinfection, particularly in the context of AMR infections, and to determine what can be done to ensure MT is more effectively used in the future to improve patient outcomes and manage the growing problem of AMR. METHOD: For this investigation, a qualitative review of case studies using MT against AMR infections and a quantitative analysis of randomised control trials (RCTs) were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. RESULTS: Analysis showed that MT is highly effective against a range of infections and wound types, and compares well against conventional therapies. The low use of MT may be due in part to the documented 'yuck factor', often associated with maggots as well as misconceptions around the cost, efficacy and accessibility of MT. To overcome these factors, more RCTs on the spectrum and efficacy of MT across various clinical manifestations are needed, as well as professional and public engagement campaigns. CONCLUSION: MT is an underused therapy, particularly regarding AMR infections, and expanding its use in these circumstances appears warranted. MT could play a vital role in conserving the efficacy of the existing pool of antimicrobials available and should be considered in the development of antimicrobial stewardship programmes. DECLARATION OF INTEREST: This work was supported by the Swansea Employability Academy, Swansea University (internal funding). The authors have no conflicts of interest to declare.

Use of biosurgery for the treatment of foot ulcers infected with therapy-resistant bacteria: a case report.

Biosurgery (larval therapy) has been used for centuries. However, in recent times, this treatment has been replaced with the use of antibiotics for the treatment of wounds. Due to increasing antibiotic resistance, larval therapy is once again coming to the fore as an effective and efficient treatment. Due to the increasing ageing population, along with an increase in patients with arterial occlusive disease, diabetes and immobility, the number of patients with hard-to-heal wounds will increase. The stressors associated with wounds, such as pain, limited physical functionality, depression and social withdrawal, have a negative impact on patient quality of life. This case report documents the performance of biosurgery in a patient with multimorbidities.

Evaluating nursing opinion and perception of maggot therapy for hard-to-heal wound management.

OBJECTIVE: Maggot therapy (MT) or larval debridement therapy is a recognised, effective but underutilised treatment for the management of hard-to-heal wounds and infected ulcers. It is available on NHS prescription in the UK, where wound management is predominantly nurse-led. Anecdotal reports and published literature suggest that nurses may be reluctant to utilise the therapy. The aim of this study was to evaluate the feelings and opinions of nurses regarding the use of MT. METHOD: The first stage of this mixed-methods study was a focus group held to discuss MT and opinions of specialist nurse clinicians. Next, an anonymised web-based online survey was launched through the Nursing Times journal and distributed through social media targeting all nurses. Finally, in-depth interviews were held with specialist and generalist nurses. RESULTS: Awareness of MT among all nurses was extremely high. A breakdown of results showed that MT was much more highly regarded by wound specialist nurses than non-wound specialist nurses. The latter exhibited a greater level of reluctance to administer the therapy, with almost one-third of these nurses surveyed saying they found maggots disgusting and that the idea of MT made their skin crawl. In-depth interviews revealed that a lack of knowledge about MT was a prime concern. CONCLUSION: Wound specialist nurses are more likely to embrace MT than non-wound nurse specialists, who report a varying degree of wariness to MT. Our study highlights a need for better education and training in MT for all nurses, to address issues with acceptance and willingness to treat or help treat patients with hard-to-heal wounds which are suitable for MT.

An exploration of public perceptions and attitudes towards maggot therapy.

OBJECTIVE: The aim of the study was to explore public opinion and perceptions of maggot therapy (larval therapy), a treatment option for hard-to-heal wounds. METHOD: The study used a mixed-method approach to obtain quantitative and qualitative data. A focus group was convened to explore opinions and views of maggot therapy with a small group of members of the public. Analysis of emerging themes from the focus group was used to design an anonymised web-based survey, which was made available online to members of the public through email and social media. RESULTS: The focus group participants identified four key themes concerning the acceptability of maggot therapy. The subsequent online survey was completed by 412 participants, analysis of which revealed some worries and fears. Only 36% of survey participants agreed that they would accept maggot therapy as a first choice for a hypothetical painful wound, although this number increased with wound severity. The most predominant concerns regarding maggot therapy were sensation and a feeling of disgust associated with the therapy. However, participants could see some benefits to maggot therapy. CONCLUSION: Our study showed that public perception of maggot therapy is varied. Survey participants expressed worries and fears associated with its use. However, positive relationships existed between knowledge scores and potential acceptability of maggot therapy, suggesting that information dissemination and education may be an important factor in public perception and acceptability of maggot therapy.

Health professionals' perceptions of maggot debridement therapy.

BACKGROUND: Maggot debridement therapy (MDT), or the use of maggots in dead tissue removal, has been shown to be beneficial in wound healing. Yet MDT in the US is often only used once conventional debridement methods have failed. METHOD: In this study, nine health professionals, experienced in MDT, were interviewed in order to identify and analyse the perceived societal barriers to MDT acceptance and usage in the US. RESULTS: Through qualitative analysis, using the grounded theory framework, this study found that among those interviewed, insurance reimbursement restrictions and stigmatisation of medicinal maggots were the factors driving resistance to MDT use. CONCLUSION: Specifically, the 'yuck' factor and the perception of MDT as an 'ancient' modality contributed towards MDT stigma; in addition, lack of outpatient insurance coverage deterred MDT use. These findings provide useful information regarding the perceptual and systemic barriers that prevent greater acceptance of MDT. Ultimately, these barriers must be understood if we are to facilitate MDT implementation and improve MDT usage in the future.

What is the effect of larval therapy on the debridement of venous leg ulcers? A systematic review.

AIM: To determine the impact of larval therapy on the debridement of venous leg ulcers, in comparison to other debridement methods or no debridement. METHOD: Using systematic review methodology, published quantitative studies focusing on the effect of larval therapy on the debridement of venous leg ulcers were included. The search was conducted in January 2020 and updated in May 2021 using CINAHL, PubMed, Embase, and the Cochrane library, and returned 357 records, of which six studies met the inclusion criteria. Data were extracted using a predesigned extraction tool and all studies were quality appraised using the RevMan risk of bias assessment tool. RESULTS: Larval therapy was found to debride at a faster rate than hydrogel (p = 0.011, p < 0.001, p = 0.0039), have a similar effect to sharp debridement (p = 0.12, p = 0.62), and was a resource-effective method of debridement (p < 0.05, p < 0.001, p < 0.001). When larval therapy in combination with compression therapy was compared to compression alone, larvae had a greater effect on debridement (p < 0.05), however, it did not improve overall wound healing rates (p = 0.54, p = 0.664, p = 0.02). Pain levels increased during larval therapy and reduced after treatment, when compared to other standard debridement techniques. CONCLUSION: Larval therapy promotes rapid debridement of venous leg ulcers. However, further high quality randomised controlled trials, comparing larval therapy to other debridement methods for venous leg ulcers, incorporating the use of compression is required to determine the long term effects of larval therapy.

The maggot therapy supply chain: a review of the literature and practice.

Maggot therapy (MT) is the clinical application of living fly larvae for the treatment of non-healing wounds and wounds that require debridement. This systematized and expanded literature review is the first study to investigate MT through the conceptual and disciplinary framework of supply chain management. The review of 491 selected academic papers was expanded to include the grey literature and online information resources to construct a first-pass theory of the medicinal maggot supply chain. It shows that the literature to date has focused on isolated discussions of echelon-specific issues such as diet improvement and sterilization protocols in the production echelon, and the relative effectiveness of medicinal maggot application methods in the treatment echelon. There is little knowledge in the public domain regarding the transport and distribution of medicinal maggots, but existing supply chains for vaccines, blood and pathology specimens may provide learning and supply chain integration opportunities. Maggot therapy knowledge across the treatment echelon is generally substantive but there is still insufficient knowledge regarding patients' and health care providers' attitudes toward the therapy, and their experiences of receiving and administering MT. Moreover, there is no research concerned with the humane disposal of medicinal flies during production and after treatment.

What is the optimal treatment time for larval therapy? A study on incubation time and tissue debridement by bagged maggots of the greenbottle fly, Lucilia sericata.

The effective use of larvae of the greenbottle fly, Lucilia sericata, in wound debridement requires a working knowledge of how feeding changes over time. Using a laboratory assay and bagged larval dressings, the effect of incubation time on larval feeding rates and body mass was investigated for up to 120 hours at 32°C. The mass of tissue digested increased significantly in incremental 24-hour periods up to 72 hours, with no significant consumption occurring afterwards. Larval mass increased only up to 48 hours. A further test comparing the efficacy of a single 96-hour application of larvae against two consecutive 48-hour applications found that the mass of tissue digested in the latter was 14.3% higher than the former, a difference that was statistically significant. Current clinical guidance suggests a 4-day application period for bagged larvae. Based on these results, an incubation time of 72 hours (3 days) for bagged larvae would be the most effective at the study temperature. However, it is acknowledged that wound temperature can vary, whereby feeding rates would likely differ. In view of this, we conclude that a period of 3 to 4 days is optimum for the application of larvae, and current guidelines should be adhered to.

The impacts of larval density and protease inhibition on feeding in medicinal larvae of the greenbottle fly Lucilia sericata.

Larval therapy, the therapeutic use of blowfly larvae to treat chronic wounds, is primarily used in debridement. There are, however, gaps in current knowledge of the optimal clinical application of the therapy and mechanisms of action in the debridement process. Using an artificial assay, two studies were undertaken to investigate these aspects of larval debridement by Lucilia sericata Meigen (Diptera: Calliphoridae); the first studied the effects of the density of larvae on tissue digestion and larval mass, and the second considered the effects on the same parameters of incorporating protease inhibitors into the feeding substrate. The total mass of tissue digested increased with larval density until saturation was observed at 5.0-7.5 larvae/cm(2) . This range was considered optimal as lower doses resulted in the removal of less tissue and higher doses offered no additional tissue removal and appeared to exacerbate competition for feeding. In the second study, increased protease inhibitor concentration led to significant decreases in tissue digestion and larval mass, suggesting that serine proteases, particularly trypsin, may play major roles in larval digestion. Such information is important in elucidating the main constituents that make up larval digestive products and may be significant in the development of new therapies.

Evaluation of conventional therapeutic methods versus maggot therapy in the evolution of healing of tegumental injuries in Wistar rats with and without diabetes mellitus.

Larval therapy consists on the application of sterilized carrion flies larvae, reared in laboratory, on acute, chronic, and/or infected wounds in order to promote healing. Conventional methods for treating injuries include mechanical debridement or silver-based dressings; however, they are not always effective for wound healing. Larval therapy is a feasible and safe treatment for therapeutic application and, in many cases, the only and the most recommended alternative for difficult healing injuries. Thus, this study aimed to evaluate the competence of Cochliomyia macellaria F. (Diptera: Calliphoridae) as a suitable species for therapeutic application and evaluate time and effectiveness of the types of treatments most commonly used to treat integumental injuries. C. macellaria eggs were obtained from colonies established in laboratory and sterilized prior to application. Twenty-five larvae were applied for each centimeter squared of lesion. Lesions were induced in 24 Wistar rats; type 1 diabetes mellitus was induced in 12 of them. Animals were divided in four groups with three individuals each, being denominated: larval therapy, larval therapy associated with foam dressing with silver release, mechanical debridement with foam dressing silver and control group, without treatment. All treatments were applied once and held for 24 h. Medical application of larvae was found to be safe, as only dead tissue was removed, and efficient to accelerate healing process when compared to other treatments.

Safety, effectiveness and economic aspects of maggot debridement therapy for wound healing.

BACKGROUND: Maggot therapy has recently attracted considerable attention as an emerging debridement technique for wound healing. This study aimed to review the safety, effectiveness and economic evaluations of Maggot Debridement Therapy for wound healing. METHODS: To retrieve the relevant evidences, the Cochrane Library (until September 2014) was searched by appropriate keywords, using free text and Mesh. Systematic reviews, HTA reports and economic evaluation studies that compared larval therapy with other debridement therapies, such as hydrogel in patients with various kinds of ulcers in terms of side effects, the wound healing rate, the healing time, and cost per QALY, were included. RESULTS: Five studies met the inclusion criteria which showed that healing with larval therapy happened a little earlier than the usual methods and that pain perception in larval therapy was a little more than usual methods (as by anesthetic conventional methods). However, the quality of life of those patients who received larval therapy was better and they showed a greater tendency to larval therapy as it was relatively safe and had a low rate of side effects. CONCLUSION: It seems that larval therapy has several advantages such as rapid wound debridement, infection elimination, pain control and ulcer healing. The use of larval therapy has the potential to reduce side effects and decrease the need for amputation.

Multiple actions of Lucilia sericata larvae in hard-to-heal wounds: larval secretions contain molecules that accelerate wound healing, reduce chronic inflammation and inhibit bacterial infection.

In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds.

Patients' perceptions and experiences of venous leg ulceration and their attitudes to larval therapy: an in-depth qualitative study.

BACKGROUND: Venous leg ulcers are a common and distressing condition that can impair quality of life. Larval therapy has been widely promoted for the treatment of different types of chronic wounds, yet little is known about its acceptability to patients. OBJECTIVES: To explore patients' experiences of venous leg ulceration and of the acceptability of larval therapy as a treatment. DESIGN: Qualitative study, using semi-structured interviews alongside a randomized controlled trial. Interview data were transcribed and analysed for thematic content. Data were collected from April 2007 to July 2007. SETTING AND PARTICIPANTS: Eighteen people (12 men, 6 women), aged between 29 and 93 years (median age 64 years), with at least one venous leg ulcer, took part in the study. Fourteen people were recruited from two vascular clinics (one attached to a hospital and the other located in a community setting). A further four people were recruited through referral from a team of community nurses. FINDINGS: Participants portrayed lives blighted by the presence of one or more leg ulcers. The majority were willing to try 'maggots' (larvae) and able to overcome feelings of squeamishness because of their strong desire to heal their ulcers. Five people treated with larvae were included in the study. Initial improvements in the condition of their ulcers were not sustained, and two participants experienced severe pain. DISCUSSION AND CONCLUSIONS: Patients may hold unrealistic expectations that larval therapy will effect a longed-for cure for their leg ulcer(s) but an absence of healing may lead to feelings of disappointment or despair.

Sterilization of Chrysomya putoria (Insecta: Diptera: Calliphoridae) eggs for use in biotherapy.

Large-scale, quality-controlled laboratory production of fly larvae is needed for biotherapy. The objective of this study was to assess the action of glutaraldehyde on the sterilization of Chrysomya putoria eggs by applying pharmaceutical sterility tests. Egg masses with 0.600 g were divided into three parts of 0.200 g, the eggs were separated using sterile distilled water, and the suspensions obtained were mixed with activated 2% glutaraldehyde solution. After 15-min contact, the suspensions were filtered through Whatman filter paper, and the glutaraldehyde residue obtained in the filtrate was neutralized by rinsing with Tryptone Soy Broth. The treated eggs were placed aseptically on Petri dishes containing gauze moistened with sterile saline solution. About 10% of the sterilized mass was transferred to test tubes containing Tryptone Soy Broth and Fluid Thioglycollate Broth. The tubes were incubated, respectively, at 22.5 and 35.0°C for 14 d to verify egg mass sterility. The plates containing the rest of the eggs (90%) were sealed with plastic film and kept in a climatized chamber at 30°C/d, 28°C per night, 60 ± 10% relative humidity, and under a 12-h light period to assess insect viability and survival. Each experiment was carried out in triplicate using a biological class II safety cabinet. No change in color or turgidity was observed with the agent tested, proving the sterility of the product and that there was no trace of contamination. Forty larvae (in three replications) in the periods of 12, 24, and 48 h after sterilization, when transferred to diet, produced larvae, pupae, and total viability similar to the control (larvae without sterilization). However, for the 72-h treatment, larvae and total viability were significantly lower than for the other treatments. There was no significant difference for the pupal stage. The product tested was shown to be efficacious for use as a sterilizer of C. putoria eggs for all the parameters assessed.

Larval Therapy and Larval Excretions/Secretions: A Potential Treatment for Biofilm in Chronic Wounds? A Systematic Review.

Chronic wounds present a global healthcare challenge and are increasing in prevalence, with bacterial biofilms being the primary roadblock to healing in most cases. A systematic review of the to-date knowledge on larval therapy's interaction with chronic-wound biofilm is presented here. The findings detail how larval therapy-the controlled application of necrophagous blowfly larvae-acts on biofilms produced by chronic-wound-relevant bacteria through their principle pharmacological mode of action: the secretion and excretion of biologically active substances into the wound bed. A total of 12 inclusion-criteria-meeting publications were identified following the application of a PRISMA-guided methodology for a systematic review. The findings of these publications were qualitatively analyzed to provide a summary of the prevailing understanding of larval therapy's effects on bacterial biofilm. A further review assessed the quality of the existing evidence to identify knowledge gaps and suggest ways these may be bridged. In summary, larval therapy has a seemingly unarguable ability to inhibit and degrade bacterial biofilms associated with impaired wound healing. However, further research is needed to clarify and standardize the methodological approach in this area of investigation. Such research may lead to the clinical application of larval therapy or derivative treatments for the management of chronic-wound biofilms and improve patient healing outcomes at a time when alternative therapies are desperately needed.

A positive association of larval therapy and hyperbaric oxygen therapy in veterinary wound care.

The treatment of cutaneous wounds is part of the veterinary routine from initial scientific reports due to being regularly present condition. Currently, several types of treatments are available to accelerate the healing process. This report presents the case of a dog with multiple lesions in the thoracic limbs resulting from a car accident, who underwent larval therapy and hyperbaric oxygen therapy (HBOT). The animal was a 2-year-old female mixed breed dog presenting severe skin degloving, fracture in the left thoracic limb (LTL), with abrasion lesions and dislocation in the right thoracic limb (RTL). The animal underwent multiple modality therapies, such as HBOT sessions associated with larval therapy; even after the LTL presented gangrene, this treatment resulted in optimal viability of the non-necrotic tissue adjacent to the gangrene. Due to chronic pain unresponsive to drug control and the presence of a fracture at a location where a possible exoprosthesis was supposed to be fixed, the LTL ended up being amputated. There are several reports of the use of HBOT or larval therapy in traumatized limbs; however, the combination of both therapies has not been previously described in the veterinary literature. Thus, we demonstrate through this report that it was possible to quickly recover the animal with good wound resolution through tissue oxygenation and a healthy granulation bed, both provided by the therapeutic combination.

Larval excretion/secretion of dipters of Lucilia cuprina species induces death in promastigote and amastigote forms of Leishmania amazonensis.

Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Larval excretion/secretion (ES) of the larvae of flies of the Calliphoridae family has microbicidal activity against Gram-positive and Gram-negative bacteria, in addition to some species of Leishmania. Our study aimed at assessing the in vitro efficacy of Lucilia cuprina larval ES against the promastigote and amastigote forms of Leishmania amazonensis, elucidating possible microbicidal mechanisms and routes of death involved. Larval ES was able to inhibit the viability of L. amazonensis at all concentrations, induce morphological and ultrastructural changes in the parasite, retraction of the cell body, roughness of the cytoplasmic membrane, leakage of intracellular content, ROS production increase, induction of membrane depolarization and mitochondrial swelling, the formation of cytoplasmic lipid droplets and phosphatidylserine exposure, thus indicating the possibility of apoptosis-like death. To verify the efficacy of larval ES on amastigote forms, we performed a phagocytic assay, measurement of total ROS and NO. Treatment using larval ES reduced the percentage of infection and the number of amastigotes per macrophage of lineage J774A.1 at all concentrations, increasing the production of ROS and TNF-α, thus indicating possible pro-inflammatory immunomodulation and oxidative damage. Therefore, treatment using larval ES is effective at inducing the death of promastigotes and amastigotes of L. amazonensis even at low concentrations.

Evaluation of Larval Therapy Compared to Antibiotic Therapy in the Treatment of Skin Wounds in Rabbits.

Larval therapy (LT) is a therapeutic modality that uses larvae of necrophagous flies for the treatment of wounds. The use of this therapy presents several benefits, due to the action of the larvae that remove necrotic tissue selectively, exercising antimicrobial action, and promoting healing. There are situations in which LT proves to be the only or the best alternative for the patient, such as wounds infected by multidrug-resistant microorganisms or when treatment difficulties may lead to an indication for amputation. The purpose of this study was to compare the efficiency of LT, using larvae of Chrysomya megacephala, with that of antibiotic therapy in the treatment of cutaneous wounds infected with Pseudomonas aeruginosa. Twenty-four rabbits were used to perform the experiment, distributed in four groups: group 1, induced wound without bacterial infection; group 2, induced wound with bacterial infection; group 3, induced wound with bacterial infection and antibiotic therapy; group 4, induced wound with bacterial infection and LT. The macroscopic, microscopic, and statistical analyses indicated that LT was as effective as antibiotic therapy in wound healing.

Recalcitrant Foot Ulceration in a Patient With Type 1 Diabetes Mellitus.

We describe the case of a middle-aged woman with type 1 diabetes mellitus who presented to the emergency department with diabetic ketoacidosis. An intravenous cannula was inserted into the veins of the dorsum of the right foot due to difficulty in obtaining intravenous access in the upper limb for managing diabetic ketoacidosis. Our patient developed edema and bullae on the dorsum of the right foot and received intravenous antibiotics for bullous cellulitis. Our patient developed ulceration on the dorsum of the right foot and over the next few months was admitted to hospital on several occasions with infected foot ulceration, which required several courses of intravenous antibiotics, larval therapy and surgical debridement of the necrotic eschar and slough. With regular review in the multidisciplinary diabetic foot clinic, the foot ulceration finally healed in eight months. This case highlights the importance of avoiding trauma in any form to the feet of people with diabetes even if aseptic techniques are taken.

Investigation of antimicrobial effects of treated Lucilia sericata larvae extract on bacteria.

BACKGROUND AND OBJECTIVES: Larval therapy refers to the use of Lucilia sericata larvae on chronic wounds, which is a successful method of chronic wounds treatment. The secretions of these larvae contain antibacterial compounds and lead to death or inhibition of bacterial growth. MATERIALS AND METHODS: In this study, we investigated the antibacterial effects of Lucilia sericata larvae secretions which were in sterilized and multi antibiotic-resistant bacteria-treated forms on Gram-positive Bacillus subtilis bacteria and Gram-negative Escherichia coli bacteria. In the following, we evaluated changes in gene expression of lucifensin and attacin during treatment with multi antibiotic-resistant bacteria. Investigation of the antibacterial effect was carried out using optical absorption and antibiotic disk diffusion in order to study the expression of the aforementioned genes. RESULTS: The results of this study showed that E. coli-treated larvae were able to inhibit the growth of E. coli and secretions of B. subtilis-treated larvae and were also able to inhibit the growth of B. subtilis. Gene expression of antibacterial peptides in multi antibiotic-resistant bacteria-treated larvae was increased in comparison to non-treated larvae. CONCLUSION: Due to the significant antibacterial potency of bacteria-treated larvae secretions, the secretions can be a suitable candidate as a drug against antibiotic resistant bacteria, but additional tests are required. Since the antimicrobial peptides of insects have not yet produced any resistance in human pathogenic bacteria, they can be considered as a promising strategy for dealing with resistant infections.