Maggot debridement therapy: A practical review

Abstract

Maggot debridement therapy (MDT) has a long and well‑documented history. Once a popular wound care treatment, especially prior to the discovery of antibiotics, modern dressings or debridement techniques, MDT fell out of favor after the 1940s. With the increasing prevalence of chronic medical conditions and associated complex and difficult-to-treat wounds, new approaches have become necessary to address emerging issues such as antibiotic resistance, bacterial biofilm persistence and the high cost of advanced wound therapies. The constant search for a dressing and/or medical device that will control pain, remove bacteria/biofilm, and selectively debride necrotic wound material, all while promoting the growth of healthy new tissue, remains elusive. On review of the current literature, MDT comes very close to addressing all of the previously mentioned factors, while at the same time remaining cost‑effective. Complications of MDT are rare and side effects are minimal. If patients and providers can look past the obvious anxiety associated with the management and presence of larvae, they will quickly see the benefits of this underutilized modality for healing multiple types of wounds.

The following core competencies are addressed in this article: Medical knowledge, Patient care, Practice‑based learning and improvement.

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© 2018 International Journal of Academic Medicine | Published by Wolters Kluwer - Medknow 21
Maggot debridement therapy: A practical review
Ashley Jordan1, Neeraj Khiyani2, Steven R. Bowers3, John J. Lukaszczyk1,3, Stanislaw P. Stawicki4
Departments of 1Surgery and 4Research and Innovaon, St. Luke’s University Health Network, 2Medical School of Temple/St. Luke’s
University Hospital Campus, 3Wound Care Center, St. Luke’s University Health Network, Bethlehem, PA, USA
Review Article
INTRODUCTION AND HISTORICAL
PERSPECTIVE
The use of maggots in wound healing is among
the best‑studied direct medical applications of
invertebrates.[1,2] For centuries, leeches, maggots,
and various invertebrate‑based medicinal products
and treatments have been used in traditional
medical practices worldwide. There is evidence
for the medical use of maggots dating back to the
1500s with documentation from Ambroise Paré
(1509–1590), Dominique Jean Larrey (1766–1842),
as well as surgeons in the Confederate Army during
the US Civil War.[3] During World War I, wounds
infested by maggots were commonly seen among
battlefield soldiers, as reported by William S. Baer,
a notable physician and surgeon of that era.[4] He
noted that wounds infested with maggots did not
appear to be equally infected or swollen when
Maggot debridement therapy (MDT) has a long and well-documented history. Once a popular wound care
treatment, especially prior to the discovery of antibiotics, modern dressings or debridement techniques,
MDT fell out of favor after the 1940s. With the increasing prevalence of chronic medical conditions and
associated complex and difficult-to-treat wounds, new approaches have become necessary to address
emerging issues such as antibiotic resistance, bacterial biofilm persistence and the high cost of advanced
wound therapies. The constant search for a dressing and/or medical device that will control pain, remove
bacteria/biofilm, and selectively debride necrotic wound material, all while promoting the growth of healthy
new tissue, remains elusive. On review of the current literature, MDT comes very close to addressing all of
the previously mentioned factors, while at the same time remaining cost-effective. Complications of MDT
are rare and side effects are minimal. If patients and providers can look past the obvious anxiety associated
with the management and presence of larvae, they will quickly see the benefits of this underutilized modality
for healing multiple types of wounds.
The following core competencies are addressed in this article: Medical knowledge, Patient care,
Practice-based learning and improvement.
Keywords: Clinical review, larval therapy, maggot debridement therapy, wound care
Abstract
Address for correspondence:
Dr. Stanislaw P. Stawicki, Department of Research and Innovaon, St. Luke’s University Health Network, Bethlehem, PA 18015, USA.
E‑mail: stawicki.ace@gmail.com
Received: 16.02.2018, Accepted: 14.03.2018
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DOI:
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How to cite this article: Jordan A, Khiyani N, Bowers SR, Lukaszczyk JJ,
Stawicki SP. Maggot debridement therapy: A practical review. Int J Acad
Med 2018;4:XX‑XX.
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Jordan, et al.: Maggot debridement therapy
22 International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018
compared to non‑maggot bearing wounds. Moreover,
maggot‑containing wounds were described as having
clean and healthy appearing “pink granulation tissue,”
prompting Baer to clinically apply and report on early
maggot debridement therapy (MDT) in the setting
of complicated wounds and osteomyelitis.[3‑5] Early
results of his MDT experiences were published in
the late 1920s and early 1930s.[4,6] Within 5 years
of Baer’s groundbreaking work, it was estimated
that >1000 American, Canadian, and European
surgeons have adopted MDT in their wound care
practices.[4,7] While the majority of doctors were
pleased with MDT, some of the drawbacks included
difficulty obtaining maggots, the expense ($5 in
1933), and the tedious effort required to construct a
restrictive dressing that would prevent maggots from
leaving the wound site.[8]
The use of MDT thrived until the development
and introduction of penicillin in the 1940s.[4]
Osteomyelitis and soft tissue abscesses, primary
indications for MDT, became less common as a
result of increasingly widespread early treatment
of infections with antimicrobial agents such as
sulfonamides and penicillin.[4] By the 1950s, the
use of MDT decreased markedly, likely due to the
combination of the introduction of antibiotics,
concurrent improvements in surgical techniques, and
general advances in wound care.[4] Maggot therapy
became a “last resort” treatment used in cases where
antibiotics, surgery and modern wound care failed to
achieve adequate or complete healing.[9]
In recent years, MDT has experienced resurgence due
to the appearance of highly specific circumstances.
More specifically, the emergence of antibiotic
resistance prompted a renewed search for alternative
approaches to managing chronically infected wounds.
[10,11] At the same time, the availability of better
chemical disinfectants, advanced wound coverage
materials, and the widespread availability of reliable
overnight shipping services, made the application
of MDT increasingly attractive through the advent
of “germ‑free” maggots that can be quickly and
inexpensively delivered to the treatment location, and
applied to the wound using custom‑made, cage‑like
dressings.[10,12]
Further advances in this area came in 2004 when the
U.S. Food and Drug Administration (FDA) approved
MDT as a “prescription only” treatment; more
specifically, maggots were approved as a single‑use
“medical device.”[4,5,13] In some other countries, such
as the UK, maggots are actually regulated as a drug.[4]
The U.S. FDA official indications for maggot therapy
are for “debriding chronic wounds, such as pressure
ulcers, venous stasis ulcers, neuropathic foot ulcers
and nonhealing traumatic, or postsurgical wounds.”[9]
Today, any licensed physician in the U.S. can prescribe
MDT.[9]
With MDT becoming increasingly popular, scientific
studies have led to the defining and recognition
of four major “actions” associated with this form
of wound therapy: Debridement, disinfection,
stimulation of healing, and biofilm elimination.
[4,14] Arora et al. demonstrated that the antibacterial
activity in excretions/secretions of Lucilia cuprina
maggots seems to act synergistically with concurrent
antibiotic treatment for Staphylococcus aureus.[15] It has
also been postulated that maggot secretions may have
an anti‑inflammatory effect on cutaneous wounds.[16]
Increasing awareness of clinical benefits of MDT led
to more targeted, evidence‑based use of this modality
for “niche indications” such as problematic wounds,
diabetic ulcers, venous ulcers, chronic pressure ulcers,
reduction of bacterial load in wounds, osteomyelitis,
cancer, and burns.[10,17‑23]
METHODS
A comprehensive query of major medical search engines
was conducted, including Bioline International,
EBSCOhost, Google™ Scholar, and PubMed. The
following list of search terms, in various combinations
was used: “maggot,” “wound,” “maggot debridement,”
“maggot debridement therapy,” “larval debridement
therapy.” Related and associated articles, when
available, were also included after critically reviewing
their content for relevance and quality. Literature
reports most closely associated with the focus of this
review were included as part of the general discussion,
topic‑specific considerations, or both. In addition,
wound type‑specific references were tabulated
according to the corresponding clinical subject area
[Table 1][31,33,42,62,68,69,72,73,75,76,83,89,102,104,109‑111].
MAGGOT BIOLOGY
Maggots are fly larvae or immature flies, just as
caterpillars are immature butterflies or moth larvae.[9,22,23]
On hatching, 1st stage larvae are roughly 2 mm long and
grow to about 5 mm before shedding their skin. The
2nd stage larvae grow to about 10 mm before they shed

Jordan, et al.: Maggot debridement therapy
International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018 23
Table 1: Listing of selected literature sources in each major clinical category discussed in this review. The table concludes with
a listing of reported complications of larval therapy
Study (reference) Year Type of report Number of patients Clinical details
Diabetic wounds
Sherman[68] 2003 Retrospective
cohort
18 MDT was more effective and efficient in debriding nonhealing foot
and leg ulcers in male diabetic veterans than conventional care
Marineau et al.[62] 2011 Case series 23 MDT resulted in favorable outcomes in 74% of patients. Six formed
granulation tissue over exposed tendons, preventing the need for
tendon excision
Tian et al.[69] 2013 Meta-analysis 356 Current evidence does not support routine MDT application for
diabetic wounds. Larger studies are needed to assess the better define
benefit (s) safety of MDT in the treatment of diabetic foot ulcers
Venous ulcers
Dumville et al.[33] 2009 Randomized,
controlled trial
267 Larval therapy did not improve the rate of healing or reduce bacterial
load. However, it did reduce time required to debride
McInnes et al.[72] 2013 Case report 1 The report suggests that MDT may have utility in the setting of a
venous ulcer contaminated with multidrug-resistant organisms
Davies et al.[73] 2 015 Randomized
control trial
40 A randomized comparison of MDT + compression versus
compression therapy alone in the management of venous ulcers.
Although wound debridement was more efficient in the MDT group,
no subsequent improvement was noted in ulcer healing
Arterial ulcers
Nordström et al.[75] 2009 Case report 1 Authors describe the use of MDT in a palliative setting at home
to decrease odor from a gangrenous wound. The report also
demonstrates the use of MDT in the setting of an arterial ulcer.
Igari et al.[76] 2013 Retrospective
cohort
16 The study suggests that patients with an ankle-brachial index <0.6
may be less likely to benefit from MDT. History of peripheral artery
disease by itself was not considered a contraindication to MDT
Burns
Wu et al.[83] 2012 Case report 1 The case demonstrates that MDT is a viable alternative to surgical
debridement of infected wounds, especially when the latter may be
contraindicated
Cancer
Lin et al.[31] 2015 Case report 1 The case describes the use of MDT in Kaposi’s sarcoma wound
to avoid amputation and possible death from infection. MDT also
provide a bridge that allowed chemotherapy and antiretroviral
therapy to become effective
Nwaeburu et al.[42] 2016 Case series 5 The authors present five cases where MDT was used to treat, but not
necessarily cure, nonhealing wounds and ulcers caused by
superficial tumors. MDT was found helpful in reducing tumor size
Gericke et al.[102] 2007 Case report 1 The case describes an 82-year-old-male who developed an orbital
infection following left orbital exenteration. His wound therapy
utilized Lucilia sericata maggots, placed within the orbital wound,
contained in a biobag. Each treatment involved 50 larvae, and after
second larval application of 4 days, the orbit was free of purulence.
Local wound treatment involving twice daily azidamfenicol was
continued to prevent recurrent infection
Less common/proposed applications
Pliquett et al.[110 ] 2003 Case report 1 Management of wounds associated with calciphylaxis in a
53-year-old-woman is described. MDT was utilized as “last
resort therapy” and the patient died from recurrent wound
infections, sepsis, and exacerbations of renal failure. It
is proposed that MDT be utilized earlier in the course of
calciphylaxis (e.g., when ulcerations initially appear)
Borst et al.[89] 2014 Case report 1 The authors report the use of MDT to treat elephantiasis. The case also
describes hyperammonemia as a potential side effect of MDT in humans
General/multipurpose applications
Steenvoorde
et al.[111 ]
2007 Case series 101 A total of 117 infected wounds with signs of gangrenous of
necrotic tissue were present in 101 study patients. Within
this group, 72 patients were classified as high-risk for
surgery (e.g., ASA III or IV). Overall, 69% of patients had good clinical
results. In terms of specific diagnoses, all wounds of traumatic
origin healed completely while all wounds with septic arthritis failed
to respond to MDT. Multivariate analysis demonstrated that chronic
limb ischemia (OR, 7.5); the depth of the wound (OR, 14.0); and
patient age >60 years (OR, 7.3) negatively affected outcomes
Contd...

Jordan, et al.: Maggot debridement therapy
24 International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018
their skins to become 3rd stage larvae. The 3rd stage
grows to approximately 15–20 mm before wandering
off as prepupae.[22] Apart from the change in size, there
is little variation among the three stages of larvae. The
most distinctive feature separating larvae of different
stages is the structure of the posterior spiracles, through
which the larvae respire.[22] Figure 1 provides a simplified
overview of relevant larval developmental biology.
The larval, or maggot, stage of fly development is the
primary feeding stage.[24] Fly larvae are very efficient
feeders, with specialized mouth hooks allowing them
to literally rake in decaying or necrotic flesh.[25] Their
rear ends consist of a chamber, in which their anus and
posterior spiracles (used for breathing) are located.[25]
Between their heads and their tails there is a muscular,
segmented body, a simple intestine and a pair of
proportionately very large salivary glands.[26] Larvae
are covered by spines that scrape along the wound and
help loosen debris.[27,28] They have mandibles which
help with maggot movement and contrary to popular
belief, are not involved in the consumption of tissue.
[26] Instead, maggots secrete and excrete alimentary
enzymes which begin digestion of necrotic tissue
outside their body.[27] Various components of these
secretions include allantoin, sulfhydryl radicals, calcium,
cysteine, glutathione, embryonic growth‑stimulating
substance, growth‑stimulating factors for fibroblasts,
carboxypeptidases A and B, leucine aminopeptidase,
collagenase, and serine proteases.[29,30]
The movement of the maggot over the wound, spreading
its alimentary secretions as it goes, further increases
debridement activity.[31,32] In fact, an in vivo study
demonstrated that larval therapy was associated with
faster debridement process than hydrogel application.[33]
The digestive enzymes also have the ability to prevent,
inhibit, and break biofilms of many bacteria, except
pseudomonas and some other Gram‑negative pathogens,
commonly found on prosthetics.[34,35] Maggot enzymatic
digestion can be very intense, leading to focal liberation
of significant amounts of heat within the center of the
wound.[36] As a result, actively feeding maggots often
migrate to the edge of the wound to cool down. The
liberation of heat increases both the rate of putrefaction
and the rate of digestion.[22] Cazander et al. demonstrated
that thermal changes within maggots’ enzymes may
help facilitate their ability to reduce the activation of the
human complement system.[37]
Not all fly species are safe and/or effective for use
in medical applications. The flies that are most
commonly utilized for maggot therapy are sheep
blowflies (Calliphoridae) and the species most
commonly used is Phaenicia (Lucilia) sericata, the
green blowfly.[38,39] This specific fly has been managed
in pure culture for over 20 years,[23] with efforts
ongoing to create transgenic Lucilia sericata larvae
capable of producing a human growth factor.[39]
Studies on the application of other fly species, such
as Protophormia terraenovae, L. cuprina, L. illustris, and
Phormia regina have also been published.[18,40,41]
EFFECTS OF MAGGOT DEBRIDEMENT THERAPY
ON HUMAN TISSUE
On a molecular level, MDT has been found to influence
three major processes: angiogenesis, inflammation,
Table 1: Contd...
Study (reference) Year Type of report Number of patients Clinical details
Reported complications of MDT
Guerrini[104] 1988 Animal study 12 Sheep infested with Lucilia cuprina larvae suffered from ammonia
toxicity and alkalosis which can cause immunosuppression
Steenvoorde and
van Doorn[109]
2008 Case report 1 Clinical report of massive hemorrhage associated with MDT
Borst et al.[89] 2014 Case report 1 The authors report hyperammonemia as a potential side effect of
MDT in humans
MDT=Maggot debridement therapy, ASA=American Society of Anesthesiologists, OR=Odds ratio
Figure 1: Life cycle of a blowy (Source: Cleveland Museum of Natural
History, reproduced with permission; URL: https://www.nlm.nih.gov/
visibleproofs/galleries/technologies/blowy.html)

Jordan, et al.: Maggot debridement therapy
International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018 25
and cell migration.[42] Three proangiogenic factors
have been identified in maggot secretions: l‑histidine,
3‑guanidinopropionic acid, and l‑valinol.[42] Dried
secretions from L. sericata larvae increased wound
capillary density and VEGF‑A mRNA protein
expression in a rat model.[43] In addition, the presence
of maggot secretions may be associated with increased
production of pro‑angiogenic growth factors from
anti‑inflammatory macrophages,[44] as well as the
differentiation of macrophages and monocytes. In
one study, larval secretions influenced monocytes to
differentiate into anti‑inflammatory macrophages.[44]
Another study showed that maggot secretions inhibit
the production of pro‑inflammatory cytokines
(e.g., tumor necrosis factor‑alpha) while upregulating
anti‑inflammatory cytokines (e.g., interleukin‑10)
in dose‑dependent fashion, likely through a
cAMP‑mediated process.[45]
Cazander, et al. collected samples of larval excretions
from disinfected maggots.[37] When added to donated
human sera from preoperative and postoperative
patients, these excretions resulted in decreases
in complement protein (C3 and C4) activation
by up to 99% (preoperative group) and up to
55% (postoperative group), pointing to a powerful
effect of MDT on complement‑mediated inflammatory
response.[37] Researchers are currently working
to isolate modulators of inflammation in maggot
excretions in hopes to identify clinically relevant
substances affecting not only complement activation
but also the proteolytic, antimicrobial, and growth
promoting activity of MDT.[4,5] Among other
potentially beneficial actions of larval secretions, the
presence of increased microvascular epidermal cell
migration was shown.[46]
MEDICAL RATIONALE FOR MAGGOT
DEBRIDEMENT THERAPY
The increasing prevalence of chronic medical
conditions and nonhealing wounds is one of the
consequences of the ability of modern medical
advances to prolong life.[4] Diseases that were once
fatal have evolved into chronic ailments that result
in cardiovascular risk factors associated with the
emergence of nonhealing wounds.[47] Given current
demographic trends, the number of susceptible
patients is bound to increase, especially among
populations that actively use pharmacological
modulators of wound healing.[4,48] Because of the
growing need for effective clinical approaches
to chronic wound management, numerous new
treatment modalities were introduced over the
past two decades, including hyperbaric oxygen
administration, negative pressure wound therapy,
topical growth factor applications, enzymatic wound
debridement, and many others.[49‑52]
In general, effective wound care begins with
properly conducted debridement, which in turn
results in a lower infectious burden and improved
wound status through the removal of necrotic,
contaminated tissue and microbial biofilm.
Mechanical, surgical, autolytic as well as enzymatic
methods have all been utilized as mechanisms for
debridement.[53,54] Each of these techniques has
associated disadvantages such as limited efficacy,
need for anesthesia, complaints of significant pain
as well as mechanical and/or cellular damage to the
underlying healthy tissue.[40]
MDT is the intentional application of live, “medical
grade” fly larvae to wounds to effect debridement,
disinfection, and ultimately wound healing.[4,55] The
process begins with predetermined species of maggots
undergoing chemical disinfection. Historically, the
availability of inexpensive, well‑contained, viable, and
germ‑free maggots has been a major barrier to wider
implementation of MDT.[4] Improved disinfectants
and rearing techniques have simplified the production
of germ‑free maggots.[4,23] Expeditious delivery of
maggots is now possible through multiple overnight
courier services.
Figure 2: An example of a “connement” dressing, with the wound itself
serving as the bottom of the “container” that holds the larvae. Applied
circumferentially around the cutaneous wound edges is the protective
hydrocolloid sheet, over which the netting material is placed. Once
secured with adhesive tape, the top portion of the dressing effectively
prevents larvae from migrating out of the wound

Jordan, et al.: Maggot debridement therapy
26 International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018
Modern dressing materials have simplified the larval
debridement procedure and minimized the risk of
uncontained maggots.[4] Appropriately fashioned
dressings now consist of improved adhesives and
synthetic materials which provide maggots with an
environment suitable for debridement while preventing
uncontrolled migration and patient/provider
discomfort. There are two major variants of
specialized MDT dressings – the confinement and the
containment types.[4,57] In confinement dressings, the
wound floor acts as the bottom limit of the enclosure,
allowing direct maggot‑to‑wound contact [Figure 2].
In containment dressings, maggots are enclosed
within a sealed pouch [Figure 3] that is then placed on
top of the wound, with no direct maggot‑to‑wound
contact.[12,56] Although somewhat counter‑intuitive,
MDT approaches based on containment and
confinement dressings have been shown to be equally
effective.[8,33] Overall, the above evidence supports
the importance of larval secretions (in addition to
any direct mechanical action) in delivering beneficial
wound outcomes, in addition to any direct physical
interactions (e.g., larval movement and the ingestion
of necrotic material) between maggots and the wound
surface.[4,8,12,58] The FDA classification of maggots
under the label of “medical device” reflects, in a way,
the fact that maggots aggressively search the wound
bed for necrotic material, consuming more and more
necrotic tissue and gaining access to increasingly
deeper tissue layers within the wound.[4,59] Chambers
et al. provide compelling experimental evidence that
the proteinases present in larval excretions/secretions
help in the breakdown of fibrin and play a role in
the subsequent remodeling of extracellular matrix
components.[60] Zhang et al. further suggest that
fatty acid extracts from L. sericata larvae may
promote wound healing by enhancing angiogenic
activity.[43] Potential benefits of MDT are summarized
in Figure 4.
MAGGOT DEBRIDEMENT THERAPY IN DIABETIC
WOUNDS
According to the Centers for Disease Control
and Prevention (CDC), an estimated 30 million
Americans (9.4% of the U.S. population) had diabetes
in 2015.[61] This population is especially vulnerable and
susceptible to poor wound healing, with the estimated
annual cost of managing diabetic wounds in the U.S.
exceeding $20 million, including more than 2 million
workdays of lost productivity.[62] Medical costs of
treating a single diabetic ulcer can reach $10,000
and clinical nonresponse or progression of the disease
process may result in an extremity amputation, with
a median cost of $12,500.[63] Diabetic extremity
ulcers affect roughly 15% of the diabetic population,
leading to approximately 70,000 amputations
annually[4,42,61,64,65] The progression from diabetic
peripheral vascular disease to chronic nonhealing
foot ulcers to terminal amputation is all too common.
MDT can stall the progression of this condition,
improving the prognosis even in recalcitrant cases.[66]
One randomized trial suggested that MDT was more
effective than hydrogel in reducing the wound area of
diabetic foot ulcers.[67] Another prospective, randomized
study comparing the efficacy of MDT versus hydrogel
showed improved debridement efficacy, but no
difference in the rate of healing or ability to eradicate
methicillin‑resistant S. aureus (MRSA) infection.[33]
While the same investigation suggested greater amount
of ulcer‑related pain with MDT compared to hydrogel,
it also showed equivalent efficacy of loose versus
bagged larvae.[33] In yet another retrospective study
comparing changes in necrotic and total surface area of
chronic foot and leg ulcers in diabetic patients, patients
were treated with either MDT, standard medical
management, or routine surgical care.[68] Maggot
therapy was associated with faster debridement and
wound healing than its therapeutic comparators.[68]
MDT‑treated wounds saw a 50% reduction in necrotic
surface area in as few as 9 days, compared to 29 days
in the other groups. Moreover, within 2 weeks, MDT
treated wounds contained only 7% necrotic tissue
compared with 39% necrotic tissue for traditional
management. Finally, within 4 weeks, wounds in the
MDT group were completely debrided and contained
56% healthy granulation base, whereas wounds treated
with conventional therapy retained 33% necrotic tissue
coverage with only 15% granulation base.[68] At the
same time, the rate of complete wound closure was not
significantly different between MDT and non‑MDT
Figure 3: An example of a “containment” dressing or a “biobag” used
in maggot debridement therapy. The permeable bag allows larval
secretions to interact with the wound while at the same time preventing
the maggots from migrating. Modied from Williams et al.,[56] under the
terms of Creative Commons Attribution License

Jordan, et al.: Maggot debridement therapy
International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018 27
approaches.[68] Despite being limited by significant
definitional heterogeneity and small size of source
reports, a meta‑analysis comparing the effectiveness
of MDT versus non‑MDT approaches, suggested
that MDT may be superior to non‑MDT modalities
in achieving full wound healing, time to healing, and
the number of antibiotic‑free days.[69] An example of
a diabetic foot ulcer treated with MDT is provided in
Figure 5.[70]
MAGGOT DEBRIDEMENT THERAPY IN VENOUS
EXTREMITY ULCERS
Chronic venous ulcers affect approximately 2.5 million
adults in the U.S., and are characterized by the presence
of venous insufficiency, hemosiderin deposition, and
lipodermatosclerosis.[71] Traditional management
options include debridement of the ulcer, skin grafting,
venous stripping or ligation, and sclerotherapy.[71]
Despite treatment, over half of these ulcers fail to
heal after a year of therapy.[71] The application of
MDT shows some promise in this challenging area
of wound care.
In one case‑based experience with the use of MDT
in the setting of chronic venous ulceration, favorable
outcome was reported despite the presence of
multidrug‑resistant bacteria including MRSA,
vancomycin‑resistant enterococci, and multiresistant
Psuedomonas aeruginosa.[72] Following 3 weeks of
combined MDT and antibiotic treatment, wound
cultures showed no growth and the clinical team
proceeded with skin grafting plus negative pressure
wound therapy.[72] At discharge, the patient was noted
to have 90% graft take, but after several months
experienced a recurrence requiring further therapy.[72]
A randomized trial comparing the efficacy of
compression bandage alone versus compression
bandage plus MDT in the treatment of chronic venous
ulcers showed that compression plus larval therapy
improved wound outcomes in the first 4 days but
failed to affect the 12‑week healing rates.[73] Evidence
shows that if the underlying venous insufficiency is
corrected, ulcerations will heal despite the presence of
devitalized tissue, as corroborated by findings from
the VenUS II trial.[33] It has also been demonstrated
that larvae beneath the bandages may stay unharmed
during the 4 days of MDT treatment, suggesting
limited need for elaborate specialty dressings.[73]
Limitations of this study included a small sample size,
lack of long‑term result evaluation, and the potential
presence of patient/venous ulcer selection bias.[73]
MAGGOT DEBRIDEMENT THERAPY IN ARTERIAL
EXTREMITY ULCERS
Ischemia has traditionally been considered a relative
contraindication for MDT.[20] In the absence of
Figure 5: An example of a diabetic foot ulcer before, during and
after maggot debridement therapy. (a) Baseline measurement of
the extent of necrosis and initiation of treatment (day 1). Asterisks
represent the areas of tissue necrosis. (b) Patient’s foot ulcer
during active treatment with maggot therapy (day 14). The asterisks
represent areas of tissue necrosis and the arrows indicate the larvae
of Chrysomya megacephala. (c) Patient’s foot ulcer after treatment
with maggot therapy (day 43). Source: Pinheiro, et al. Indian J Med
Res 2015;141 (3):340‑2. Images used under the terms of the Creative
Commons Attribution‑Noncommercial‑Share Alike 3.0 Unported, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited
c
b
a
Figure 4: List of selected benets of maggot debridement therapy
based on the current literature review

Jordan, et al.: Maggot debridement therapy
28 International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018
adequate arterial perfusion, revascularization is
required to support wound healing.[74] If this is
not feasible, amputation may be required.[20,74]
Beyond these general guidelines, there is no formal
quantitative definition of circulatory function required
for MDT to be successful. Consequently, the utility
of MDT in the setting of arterial extremity ulcers has
been predominantly limited to defining the level of
viable tissue and thus guiding amputation planning.[20]
One clinical report suggests that the use of MDT
in ischemic extremity ulcers may have utility in the
setting of a gangrenous wound of the foot, provided
that revascularization attempts are made.[75] In that
particular case, MDT was initiated to reduce patient
discomfort and odor while trying to prevent an
amputation.[75] Following a femoro‑femoral bypass
and eight MDT treatments, necrotic soft‑tissue was
effectively debrided, and the foot wound began to
heal.[75] Another small study evaluated management
of leg ulcers in 16 patients suffering from peripheral
arterial disease, with MDT effectively facilitating
healing in 10 cases.[76] The authors determined that
ankle‑brachial index of <0.6 may be associated with
unfavorable MDT outcomes in the setting of ischemic
leg ulcers.[76]
MAGGOT DEBRIDEMENT THERAPY IN
PRESSURE ULCERS
Pressure ulcers are among the most common adverse
events seen within the healthcare setting. Although
incidence and prevalence may vary depending
on the institution and setting, it is estimated that
over 2.5 million individuals in the United States will
develop pressure ulcers annually.[77] This equates to
a significant financial burden as well as an increased
mortality rate for patients who develop this dreaded
complication.[77] In fact, the overall associated cost
is estimated to be between $9.1 and $11.6 billion,
and more importantly about 60,000 attributable
deaths.[78] The standard treatment approach consists
of appropriate “offloading” of the area of injury,
in addition to excellent nursing care and the use of
pressure redistribution devices including specialized
mattresses and seat cushions.[79] As with all other types
of wounds, debridement may become necessary, along
with appropriate specialty care management. These
ulcers may require weeks to months of debridement,
often contain extensive amount of necrotic tissue,
and can be malodorous and difficult to handle in the
outpatient setting. MDT may be used to reduce the
number of debridements required which may decrease
pain, bleeding, length of admissions, and overall costs.
In one study, looking at 103 inpatients with
145 pressure ulcers, 80% of MDT‑treated wounds
were deemed to be successfully debrided while only
48% were completely debrided using conventional
therapy alone.[80] In the same study, it was noted
that within 3 weeks the MDT‑treated wounds
contained approximately one‑third of the amount
of necrotic tissue and twice the granulation tissue
compared to nonmaggot‑treated wounds.[80] In
another small prospective controlled study looking
at eight spinal cord injury patients with pressure
ulcers that had been treated with conventional
nonsurgical approach, MDT was shown to
significantly decrease the amount of necrotic
tissue seen after 1 week, as well as reduce the
time to heal.[81] Additional clinical investigation,
looking at 25 patients with intractable wounds,
including lower extremity and pressure ulcers,
demonstrated that MDT was able to achieve
complete debridement in >88% of wounds.[82] In
all of these studies, MDT was shown to be a safe,
simple, effective, and an inexpensive alternative to
conventional therapy of pressure ulcers.
MAGGOT DEBRIDEMENT THERAPY AND BURN
INJURIES
A relatively recent case report demonstrated the
applicability of MDT in the treatment of extensive
thermal injuries.[83] A 59‑year‑old patient presented
with severe, full‑thickness burns over 60% of his total
body surface area, with concurrent extensive muscle
necrosis.[83] Following escharotomies and initial
resuscitation, debridement of necrotic muscle proved
difficult, mainly due to the lack of clear boundaries
between normal and necrotic tissue. Skin allografting
was performed, followed by the development of
fevers, abdominal distension, and generalized clinical
deterioration.[83] The allogenic skin was removed, and
extensive soft‑tissue necrosis was discovered.[83] Initial
consideration of surgical debridement was abandoned
because the amount of resected tissue would not
be compatible with meaningful functional survival.
[83] As an alternative option, MDT was utilized to
more selectively debride necrotic areas.[83] The patient
defervesced approximately 24 h after the initiation of
MDT, followed by general clinical improvement. By
day 6, large areas of granulation tissue were readily
apparent.[83] No complications were reported during the

Jordan, et al.: Maggot debridement therapy
International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018 29
follow‑up period, and subsequent serial skin grafting
was performed to cover the wounds.[83] Of interest,
the authors noted that MDT was much more effective
on necrotic muscle than on necrotic tendons, skin, or
adipose.[83]
ONCOLOGIC APPLICATIONS OF MAGGOT
DEBRIDEMENT THERAPY
Although the application of MDT in the oncology
setting does not treat cancer, this modality can provide
benefit in the following therapeutic areas: mass
debulking of necrotic tumor, drainage reduction, and
odor control.[20] Literature is scant regarding MDT use
for oncologic indications, consisting mainly of case
reports in the setting of ulcerating tumors. Despite
these limitations, some generalizations can be made.
For example, malignant tissue in inoperable ulcerating
sarcomas and breast carcinomas was noted to be readily
susceptible to the beneficial activity of maggots.[42] The
larvae attacked any abnormal structure(s) within the
wound, clearing away malignant tissue and leaving
behind healthy granulation bed.[42] In addition,
the associated odor and pain improved, with some
evidence of wound closure tendencies.[84]
In one striking case, a necrotic squamous cell
carcinoma of the face was noted to be infested with
blowfly larvae.[85] Because the wound contained no
evidence of surrounding cellulitis or adenopathy, it
was decided to leave the larvae in place, and by the
3rd day, the wound was devoid of any residual necrotic
tissue.[85] A similar case was described involving a
deteriorating squamous cell carcinoma refractory to
chemotherapy, radiotherapy, and conventional wound
management until successful MDT application.[42]
Wounds associated with Kaposi sarcoma have also
been successfully treated with MDT. Similar to
applications in other oncologic settings, larval therapy
may help debride, disinfect, and heal necrotic Kaposi
sarcoma wounds, potentially preventing morbid
outcomes such as amputation or severe soft‑tissue
infection.[31] To summarize, key palliative benefits of
MDT in the setting of difficult‑to‑treat, cancer‑related
wounds include better control of infection, odor,
drainage, and avoidance of extensive and potentially
deforming surgeries.[31]
MAGGOT DEBRIDEMENT THERAPY FOR
ELEPHANTIASIS NOSTRAS VERRUCOSA
Seen very rarely, elephantiasis nostras verrucosa (ENV)
is a dermatologic condition that complicates chronic
lymphedema.[86] It typically presents with dermal
fibrosis, hyperkeratotic, papillomatous, verrucous
lesions, often accompanied by episodic infections of
involved tissues.[87] Affected anatomic areas have been
described as having cobblestone‑like appearance in the
setting of severe, nonpitting, fibrotic edema.[88] Known
risk factors for ENV include recurrent cellulitis,
previous surgery/trauma, obesity, congestive heart
failure, and radiation exposure.[88]
In a recent case report, the use of MDT was shown
to be effective in treating ENV.[89] Over a period of
28 days, the patient underwent a combination therapy
consisting of surgical debridement and MDT for the
right lower extremity ENV.[89] Larvae were placed
over the wounds for 48–72 h at a time, allowing the
affected tissue to become soft and the hyperkeratotic
areas to slough off, with impressive end result.[89] The
authors describe transformation of dark, edematous,
woody, and malodorous tissues into much thinner,
softer, and pinker ones. Most importantly, the patient’s
pain improved significantly, restoring his ability to
ambulate.[89] Although the conventional therapy for
ENV is surgical, operative debridement can be very
difficult given the texture and tissue consistency of ENV.
Presurgical treatment with 10% salicylic acid is often
necessary to soften these lesions before debridement.
In the above‑described case, MDT was able to reduce
the presurgical preparation time from 1 month (typical
duration) to 2 days.[89] Further investigation is clearly
warranted in this highly specialized area of wound care.
COST‑EFFECTIVENESS OF MAGGOT
DEBRIDEMENT THERAPY
The approximate cost of medical maggots is currently
between $80 and $100 per treatment. Although it
may seem expensive, this range is roughly equivalent
to what it was about 90 years ago when adjusted for
inflation.[4] The majority of the cost is attributable to
labor and quality control expenditures, and although
MDT in the U.S. is generally covered by third party
payers, this remains inconsistent.[4] MDT is generally
considered both clinically and fiscally prudent due
to its documented effectiveness, simplicity, safety,
applicability to a broad range of settings (e.g., hospital,
clinic, home), and the ability for a wide range of
caregivers to apply it (e.g., physicians, nurses, patients,
and family members).[4]
It has been noted that MDT may be more cost‑effective
than conventional wound therapy in certain clinical

Jordan, et al.: Maggot debridement therapy
30 International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018
settings and/or conditions.[4,9] One study examined
cost‑effectiveness of MDT compared to other
conventional wound care approaches in the setting
of venous stasis ulcers.[9] The median cost of an
MDT treatment (including the price of larvae)
was significantly lower (£78.64) when compared
to £136.23 per‑treatment cost in the control group.[9]
In addition, the MDT group required less nursing time
per ulcer treated than the standard “hydrogel dressing”
group (three nursing visits in MDT group vs. 19
visits in the standard treatment group).[9] The median
cost of nursing per ulcer was £53.85 for standard
therapy versus £10.77 for MDT group.[9] Even after
including the cost of larvae (£58.00 per treatment)
the median amount of “dressings” was still lower for
the MDT group (£67.87 vs. £89.55).[9] When all of
the above are compiled into monthly cost data, MDT
was about 50% less expensive than the comparator
therapy (£492 including larvae vs. £1054 in the
hydrogel group).[9]
It is important to note that MDT, based on previous
observations, may be associated with better clinical
outcomes. The fact that debridement occurred more
rapidly in patients undergoing MDT is difficult to
quantify from economic standpoint.[40] However,
the combination of indirect benefits of MDT
(e.g., more effective debridement) and lower reported
costs (e.g., clinical materials and labor) presents a
compelling argument in favor of larval therapy.[4,9] One
can likewise extrapolate that MDT, associated with
more rapid debridement, would also be associated
with an earlier hospital discharge and thus financial
benefits of shorter duration of stay.
ADVERSE EFFECTS OF MAGGOT DEBRIDEMENT
THERAPY
As with other medical modalities, MDT has a number
of associated side effects and risks, from localized
tissue discomfort, to infection, to the sight of escaping
maggots.[90] By far, the most common adverse effect
of MDT is significant pain,[91,92] with approximately
5%–30% of patients reporting this complaint.[4,68,80,93]
It is important to note, however, that most patients
who complain of pain during MDT also report
some degree of “baseline” pre‑MDT pain. The skin,
especially around the wound, tends to be sensitive to
motion, pressure, and the liquefied necrotic drainage
associated with maggot secretions.[94‑96] The perception
of movement becomes more apparent after 24 h of
therapy due to increase in larval size. This uncomfortable
sensation can be ameliorated by applying fewer or
smaller larvae over the wound bed while also actively
removing larvae before they become too large.[91]
In terms of the sensory perception of pain, patients
most often report either throbbing (pressure‑like) or a
sharp (knife‑like) sensation.[20] Multimodality analgesia
can help control the pain, especially when the latter
occurs in the presence of associated hyperalgesia and
central sensitization.[97‑99] Preemptive analgesia may
also be helpful, particularly when treating patients
with known predisposition for acute‑on‑chronic pain
exacerbations.[99,100]
Some degree of anxiety is also common among both
patients and providers.[91] One survey showed that
health‑care professionals and administrators are much
more likely to be repulsed by the thought of maggot
dressings than the actual patient suffering with the
chronic wound.[4,101] Patients may have some anxiety
but are generally very accepting of MDT as a treatment
option. The most effective way of addressing patient
anxiety is by providing the recipient with more control
over their treatment.[91] The availability of 24 h/day
access to immediate and direct medical assistance can
help with anxiety. At the same time, pharmacologic
adjunctive therapy can be useful as well.[20] An
important component of the overall strategy to reduce
both patient and provider anxiety is education about
MDT, optimally with inputs from experienced wound
care experts, as well as former MDT patients.[102,103]
It has been observed that the digestive enzymes released
by maggots may be associated with the appearance of
erythema or cellulitis.[96] Mumcuoglu recommends that
this complication can be avoided by applying plaster
or hydrocolloid dressing around the periphery of the
wound.[96] Related to this local tissue reaction is the
frequently reported sensation of “tickling” or itching
of the anatomic region being treated.[96]
First documented in sheep infested with >15,000
larvae, hyperammonemia is an uncommon side
effect of MDT.[104] This ammonia toxicity as a
result of an extreme larval burden is called “blow fly
strike” that can result in reduced immune function,
encephalopathy, and coma in most severe cases.[105]
It was subsequently documented in humans by
Borst, et al.[89] The increase in ammonia itself may
be involved in the antimicrobial and wound healing
activity of MDT.[106] Borst et al.[89] also demonstrated
that serum ammonia levels trended predictably with
increases in larval load. Consequently, high larval loads

Jordan, et al.: Maggot debridement therapy
International Journal of Academic Medicine | Volume 4 | Issue 1 | January-April 2018 31
must be avoided to minimize morbidity.[20,107] It is
also recommended that a baseline serum ammonia
level be established prior to initiating MDT and that
monitoring be continued throughout treatment. Any
changes in mental status in a patient undergoing MDT
should prompt ammonia level verification. Adherence
to the recommended density of 5–10 maggots/cm2
can also help mitigate the risk of “blow fly strike.”[20]
Escaping of larvae or even mature flies is a possibility
during MDT.[10,108] Larvae do occasionally get loose
as they migrate away from the warm environment
of the wound bed in search of necrotic tissue. This
is most commonly seen when maggot dressings are
left in place for more than 48 h.[8] Transitioning to
an adult fly typically takes 1–2 weeks; the chance that
larvae would go without being noticed for such an
extended period of time is unlikely. However, cases
where dressings are intentionally or unintentionally
left in place are not out of the realm of possibility.
Another rare side effect is maggot invasion of healthy
tissue. It is important to note that only a few larval
species have been used in medical applications
with success.[107] L. sericata is the most commonly
prescribed larval type. This is primarily because it was
discovered that larvae of this species starved when only
granulation tissue remained in a wound.[84] However,
there still have been reports of L. sericata feeding on
healthy human tissue, resulting in a theory that some
strains of this species were able to retain a degree of
invasiveness in humans.[96,107]
Although no allergic reactions have been attributed
to MDT larvae, allergies to various wound dressing
materials are possible.[96] It is important to remember
that the use of nonsterile maggots can be associated
with septicemia.[96] This, in turn, highlights the
importance of ensuring the availability of high quality,
reliable sources of medically suitable larvae.
Finally, serious bleeding in a patient undergoing MDT
was reported.[109] In that particular case, the patient was
being treated with approximately 200 maggots while
at home. A visitng nurse performing a dressing change
reported severe bleeding at the wound site and rushed the
patient to the hospital. It was estimated that 500 mL of
blood was lost at the scene. During the initial evaluation
at the hospital, the wound was judged to be healing
adequately as there was granulation tissue present without
visible necrosis. Shortly afterwards, the patient’s blood
pressure fell suddenly to 72/24 mmHg, necessitating
blood transfusion and inpatient admission. Patient has
subsequently normalized and was discharged after 4 days
in the hospital, without further complications.[109] Table 1
provides a summary of complications encountered with
MDT.[31,33,42,62,68,69,72,73,75,76,83,89,102,104,109‑111]
CONCLUSIONS
Modern MDT is based on established clinical evidence
and has resulted in substantial wound care advances.
MDT is most often used in chronic, nonhealing
wounds; however, it was also found to be useful in
a variety of other specialized wound applications,
including postsurgical wounds, burns, necrotic
fungating tumors, osteomyelitis, and necrotizing
fasciitis. High‑risk medical patients, including those
with chronic diabetes and vasculopathy have benefited
greatly from MDT.
For extremity wounds, benefits of MDT may be greatest
before infection or vascular compromise become limb
threatening.[4] One of the advantages of MDT is that it
is not operator dependent.[8] Many of the drawbacks of
MDT have been successfully addressed through advances
in materials manufacturing and transportation making
maggot therapy readily available, reliable, economically
viable, and simple to implement.[4] Specialty laboratories
currently supply medical‑grade maggots to therapists
and patients in more than 30 countries.[4] Complications
of MDT, for vast majority of patients, are minimal
and easily treatable. Thus, MDT appears to be a great
tool for supplementing surgical treatment or primary
therapy in patients who are not surgical candidates.
Given many unexplored areas of clinical application of
MDT, this valuable wound management option should
be studied further.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Ethical conduct of research
Established ethical guidelines for research were utilized
during the conduct of this project. Neither IRB
approval nor informed consent were required because
no human participants were involved.
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