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Update on Managing Serious Wound Infections in Horses 3. Wounds Involving Bone

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Abstract

The first two articles in this 4-part series explored the question, Why do some infections persist and progress despite seemingly appropriate treatment?, as it pertains to wounds involving joints and other synovial structures. 1,2 Of the many possible reasons, most serious wound infections involve at least one, and usually a combination, of these factors: 3 1. extensive contamination, or bacterial burden that overwhelms the patient's resources 2. refugia which protect the bacteria from host defenses and antibiotic drugs 3. immunocompromise 4. poor perfusion 5. antibiotic insensitivity of the wound pathogen(s) These same factors, often in combination, also contribute to the persistence of wound infections that involve bone. In horses, wounds that involve bone range in severity, complexity, and long-term impact from those containing a thin sequestrum on the surface of the third metacarpus/tarsus that resolve with routine wound care after sequestrum removal, to septic osteomyelitis at the site of internal fixation that results in failure of the fracture repair and potentially in euthanasia. Yet in all cases, the principles of successful treatment are the same: • debride the devitalized or irreparably damaged bone and soft tissue • preserve and protect the vascular supply to bone and soft tissue • maintain or restore structural integrity at the site • control infection through appropriate local/regional and systemic antibiotic therapy • protect the wound from further contamination, desiccation, maceration, and trauma There are a number of review articles on the management of wounds involving bone in horses. 4-7 So, rather than plowing the same ground, this article examines some advances in wound care over the past 15 years as they relate to wound infections involving bone.
Update on Managing Serious Wound Infections in Horses
3. Wounds Involving Bone
Christine King BVSc, MANZCVS, MVetClinStud
The first two articles in this 4-part series explored the question, Why do some infections persist
and progress despite seemingly appropriate treatment?, as it pertains to wounds involving joints
and other synovial structures.1,2 Of the many possible reasons, most serious wound infections
involve at least one, and usually a combination, of these factors:3
1. extensive contamination, or bacterial burden that overwhelms the patient's resources
2. refugia which protect the bacteria from host defenses and antibiotic drugs
3. immunocompromise
4. poor perfusion
5. antibiotic insensitivity of the wound pathogen(s)
These same factors, often in combination, also contribute to the persistence of wound infections
that involve bone.
In horses, wounds that involve bone range in severity, complexity, and long-term impact from
those containing a thin sequestrum on the surface of the third metacarpus/tarsus that resolve with
routine wound care after sequestrum removal, to septic osteomyelitis at the site of internal
fixation that results in failure of the fracture repair and potentially in euthanasia. Yet in all cases,
the principles of successful treatment are the same:
debride the devitalized or irreparably damaged bone and soft tissue
preserve and protect the vascular supply to bone and soft tissue
maintain or restore structural integrity at the site
control infection through appropriate local/regional and systemic antibiotic therapy
protect the wound from further contamination, desiccation, maceration, and trauma
There are a number of review articles on the management of wounds involving bone in horses.4-
7 So, rather than plowing the same ground, this article examines some advances in wound care
over the past 15 years as they relate to wound infections involving bone.
MAGGOT DEBRIDEMENT THERAPY
Wound lavage, debridement, and drainage are essential components of treatment for infected
wounds of any type.3 When bone is infected, surgical debridement of the devitalized or
irreparably damaged bone is particularly important. Traumatized bone and associated soft tissues
can serve not only as a persistent inflammatory focus but also as a refugium for bacteria,
protecting the organisms from host defenses and antibiotic drugs, and thus preventing the wound
from healing.
For the infection to resolve and the wound to heal, sequestered bone must be removed and any
soft or discolored bone curetted down to healthy bone wherever possible. When surgical
implants are involved, such as in osteomyelitis associated with bone screws or pins, implant
removal may also be needed, as surgical implants of any type can support bacterial biofilms,8
which serve as very effective and particularly resistant refugia.
In addition, any devitalized, irreparably damaged, or extensively contaminated soft tissues must
also be debrided. Here, maggot debridement therapy (MDT) can be a useful adjunct when
complete surgical debridement would be difficult or impossible without causing damage to
viable tissues and loss of structural integrity. Medical maggots may be particularly useful in
contaminated wounds with deep or multiple tracts. The maggots cannot break down calcified
tissue and they are slow to degrade dense connective tissue such as tendons and ligaments, but
they are very effective at soft tissue debridement and wound disinfection, and their activities also
stimulate wound healing.
Mechanisms of MDT
Maggot debridement therapy, also known as biosurgery, involves the controlled application of
disinfected blowfly (Phaenicia/Lucilia sericata) larvae to a wound. The larvae selectively feed
on necrotic tissue and wound exudate, debriding affected parts of the wound and leaving healthy
tissues largely untouched.9,10
The physical activities of the maggots as they move about in the wound and the biochemical
activities of their digestive secretions and excretions have numerous benefits for infection control
and wound healing:9,10
physical debridement—although tiny (2 mm long initially), the larvae have sharp
mouthparts and are covered by small spines that mechanically rasp and loosen the tissue
over which they move; as they are attracted to necrotic tissue, the larvae are most active
in the parts of the wound most in need of debridement, including recesses that are
difficult to access surgically without extensive dissection; MDT is described as being as
effective as microsurgery for wound debridement11
chemical debridement—in the process of feeding, the larvae secrete a variety of potent
proteases (including matrix metalloproteinases), glycosidases, and DNA-ase that liquefy
necrotic tissue and fibrinous debris so it can be ingested; these debridement activities also
facilitate wound drainage
disinfection—the larvae ingest and digest bacteria and fungi when feeding, and their
secretions/excretions contain a variety of potent antimicrobial substances; as a result, the
numbers and variety of bacteria in the wound decrease during treatment, and clinical
signs of wound infection abate, often within days of beginning treatment
antibiotic potentiation—larval secretions/excretions potentiate the activities of some
antibiotics against some pathogens, such as gentamicin and flucloxacillin against
Staphylococcus aureus; for example, in an in vitro study, the minimum inhibitory
concentration (MIC) of gentamicin against S. aureus decreased 64-fold in the presence of
larval secretions12
biofilm inhibition and degradation—larval secretions and physical activities break down
existing biofilms and inhibit the formation and re-formation of biofilms8
wound healing—the physical and chemical activities of the larvae affect local cytokine,
cellular, and growth factor expression, which facilitates wound repair in the following
ways...
§ moderates the inflammatory response
§ improves tissue perfusion
§ stimulates fibroblast proliferation and migration
§ promotes angiogenesis (i.e., stimulates healthy granulation)
In other words, MDT addresses most, if not all, of the factors that contribute to the persistence of
wound infection. It has even been suggested that MDT be considered both primary and
secondary treatment in wound management, the primary action (debridement and disinfection)
being a necessary prerequisite for the secondary effects on wound healing.13 An emerging trend
in the management of very chronic wounds in humans (e.g., diabetic, ischemic, or decubital
ulcers) is "maintenance MDT," where treatment of 2–3 days' duration is repeated weekly until
wound healing is advanced.10
Antibiofilm properties
The antibiofilm properties of MDT warrant particular attention in this discussion of wound
infections involving bone. Bacterial biofilms are complex bacterial communities that can form
on any surface, both living and inanimate, including bone and surgical implants.8,14 Biofilms are
most likely to be found in chronic wounds and wounds with poor perfusion,15,16 so traumatic
wounds involving damaged bone are good candidates, particularly if some form of internal
fixation is used in fracture repair.
A fully formed or mature biofilm comprises a typically polymicrobial community of firmly
attached bacteria that produce a protective extracellular coating of polysaccharides, proteins,
glycolipids, DNA, and water.3,14 The biofilm provides a moist, stable, and nutrient-rich
environment which protects against desiccation, deluge, and other adverse physical conditions. It
also protects the bacteria within from the host's defenses and from potentially lethal
concentrations of antibiotic drugs. For example, mature biofilms increase the MIC of antibiotic
drugs against the bacteria within by up to 1,000-fold.3,14
Mature biofilms are notoriously resistant to chemical disruption by antibiotics, antiseptics,
detergents, acids, alkalis, alcohol, and reactive oxygen species (hydrogen peroxide, other
peroxidases, ozone) at concentrations that are tolerated by the host's cells.3 In addition, because
biofilm formation begins with bacterial attachment to the surface, biofilms also resist removal by
routine wound lavage. Thus, biofilm removal and inhibition by MDT8-10 is noteworthy, and
especially so for bone infections involving surgical implants that must remain in place for
structural stability during fracture repair.
In an in vitro study, maggot secretions/excretions were co-cultured with mature S. aureus and
Staphylococcus epidermidis biofilms on 3 different biomaterials: polyethylene, titanium, and
surgical stainless steel. Visible biofilms formed on all 3 materials (although least on titanium),
and the presence of maggot secretions/excretions significantly decreased the amount of existing
biofilm and inhibited further biofilm formation on all 3 materials.8 Breakdown of the
extracellular polymeric substance of the biofilm restores the antibiotic sensitivity of the bacteria
within,3,14 so using a combination of MDT and antibiotic therapy can be an effective strategy for
degrading mature biofilms and preventing their formation and re-formation in wounds.9
Clinical limitations
As mentioned above, maggots will not remove bony tissue, so MDT is useful only for soft tissue
debridement and wound disinfection, as an adjunct to surgical debridement, in wound infections
involving bone. Although the debridement of biofilms on exposed surgical implants may be a
clinical indication of MDT, deep bone infections involving surgical implants may not be
completely debrided by MDT alone. Surgical intervention may also be needed; and in some
cases, more than once.
Also of note, there are some indications that MDT may be more effective against Gram-positive
than Gram-negative infections. The antimicrobial substances secreted/excreted by the larvae, and
also the physical consumption of bacteria, are broad-spectrum and effective against even
multidrug-resistant pathogens, including methicillin-resistant S. aureus (MRSA), Enterococcus
faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, and
Escherichia coli.9,10,17-20 However, in experimental studies prompted by clinical reports,
antibacterial activity against Gram-negative wound pathogens required higher concentrations of
larval secretions.9,10,18,19 Clinically, MDT has been used successfully in the treatment of wounds
infected with Gram-negative bacteria;9,10 it may simply require more maggots and/or a longer
duration of MDT (i.e., higher concentrations of larval secretions).
The one exception may be Proteus spp., such as P. mirabilis. Both clinical and experimental
studies suggest that Proteus could be a protected organism in this fly species, perhaps through
symbiosis. Two antibacterial compounds produced by P. mirabilis have been isolated from the
larval gut of a related blowfly species, and it is suggested that Proteus may be a resident gut
microbe that contributes to the antibacterial effect of MDT.10 In support of this concept, an in
vitro study showed that maggot secretions/excretions were active against biofilms formed by
clinical isolates of S. aureus and E. cloacae, but they protected and even stimulated P. mirabilis
biofilm formation.18 In a clinical report on the use of MDT in horses, Morrison noted that wound
infection with P. mirabilis, although uncommon, resulted in the failure of MDT in those
patients.21
MDT in Equine Wounds
It may seem contraindicated to apply maggots to a deep bone infection. However, medical
maggots have been used with success in a variety of serious wound infections in horses,
including these:
osteomyelitis of the distal phalanx (P3),21-23 navicular bone,24 or proximal and middle
phalanges21
sepsis of the navicular bursa and/or distal interphalangeal joint following penetrating
injury to the solar surface of the foot21,22,24
necrosis of the collateral cartilage of P3 (quittor)21
fistulous withers22,23
chronic wounds on the metatarsus or tarsus23
draining tract associated with fracture of the tuber coxae23
osteomyelitis associated with internal fixation of a long bone fracture23
The latter case involved a 3-week-old foal with a fractured cannon bone. Wound dehiscence
exposed some of the metal implants, and MRSA was cultured from the infected tissues. The
wound healed completely after removal of 2 loose bone screws, light surgical debridement, and 2
rounds of MDT (3 days each).23
Sources and Doses
In 2004, the US Food and Drug Administration began regulating medical maggots and approved
the commercial production of P. sericata larvae as a medical device for wound debridement.a A
list of suppliers in various countries may be found at http://www.bterfoundation.org/maggotrx.
In the US, medical maggots are shipped in sterile, single-use vials, each containing 250–500
newly hatched larvae embedded in a sterile gauze pad, ready for application onto the wound.25
Larger quantities (500–1,000 larvae/vial) are available by special order for large wounds.
The recommended dose in human patients is 5–10 larvae per square centimeter of wound
surface.10,25 Published "doses" in horses ranged from 300 to 1,000 larvae per wound, depending
on the size and depth of the wound.21-24,26 In a clinical report of MDT in 41 horses and donkeys,
Lepage et al. accounted for wound depth in wounds >2 cm deep by multiplying the surface area
of the wound by the depth and then multiplying the product by 5 to arrive at the estimated
number of maggots needed for each wound.23 Their method may be depicted mathematically as:
(surface area × depth) × 5 = number of maggots per treatment
where surface area (cm sq.) = wound length (cm) x width (cm), wound depth is estimated or
measured in centimeters, and 5 represents the lower end of the recommended dose range (5–10
larvae/cm sq).
For some particularly deep or cavitary wounds, radiography or ultrasonography may be useful in
determining wound dimensions. However, it is usually sufficient to simply estimate the wound
dimensions, and if in doubt, order a larger quantity of maggots. It is probably better to have too
many maggots and discard any surplus during application than to have too few for efficient
debridement and disinfection. Larval viability is limited, so the supplier advises ordering only as
many larvae as needed for a single application. Fresh larvae must be reordered for any
subsequent applications (see below), and any unused larvae disposed of appropriately, bearing in
mind that they are live blowfly larvae.25
Applying MDT
Wound preparation
In most published reports, the maggots were applied after light surgical debridement and
irrigation of the wound,21-24 and in the case of postoperative orthopedic infections, after removal
of any loose or failed surgical implants.23 Removal of excessive slough and wound exudate is
important before the maggots are introduced to the wound, as the larvae respire aerobically9 and
they may be suffocated or drowned by thick slough or copious exudate.21,22
Along the same lines, it is also important to ensure adequate wound drainage. If necessary, a
means of spontaneous drainage must be created in the most ventral or distal portion of the
wound. Infected wounds tend to be exudative, and MDT increases exudation from the wound
bed,21,23 so spontaneous wound drainage is important for a good outcome.
The maggots are best applied to the wound the day they arrive, or within 24 hours of delivery, to
ensure their sterility and optimal viability. However, if surgical debridement caused some
bleeding, it is best to wait a few hours before applying the maggots.21,23
Concurrent use of antimicrobial agents?
It is recommended that antiseptic use on the wound bed be avoided before and during MDT,21
but experimental27,28 and clinical21 studies indicate that concurrent antibiotic therapy seems not
to interfere with MDT. For example, in an in vitro study, a gentamicin concentration of 4 mg/ml
(1,000 times the average therapeutic level) reduced larval survival in culture to only 3%, but
lower concentrations (up to 100 times therapeutic levels) were well tolerated (80–90% survival).
Cefazolin concentrations of 800 µg/ml (100 times the average therapeutic level) decreased larval
survival to 70%, but there were no significant reductions in larval survival or maturation rate
with ampicillin, ceftizoxime, clindamycin, mezlocillin, or vancomycin.27
These findings may have implications for local or regional delivery of antibiotics, such as
regional limb perfusion (RLP), where high concentrations of antibiotic in the target tissues are
the goal. However, the limited clinical data we have thus far in horses indicate that RLP with
aminoglycosides may be performed concurrently, without compromising the effectiveness of
MDT.21,24
Wound dressings
The sterile gauze pad containing the larval dose is applied directly to the wound bed and the
maggots are maintained in the wound for 2–3 days,23,25,26 and up to 7 days,21,24 at a time. The
maggots are contained in the wound by a porous dressing (e.g., gauze "4x4") or fine mesh (e.g.,
netting or stocking) that allows airflow to the larvae yet prevents their migration or loss from the
wound. Although special containment bags and dressings have been developed for use in
MDT,(a)10,23 a simple gauze pad or porous nonstick dressing covered by an absorbent wound
dressing and protective bandage is usually adequate to contain the larvae, ensure their viability,
protect the wound from further contamination, and absorb the wound exudate.21,24
"Free-range" or bagged?
Strict containment of the maggots is vital for wounds involving a body cavity, but for most
wounds involving bone, "free-range" maggots have worked best, as containment bags prevent
the physical aspects of the maggots' activities on the wound bed.10,23 Lepage et al. subjectively
compared indirect contact (use of a BioBag®) with direct contact (deposition of the maggots
directly onto the wound bed) in a variety of equine wounds and concluded that direct contact was
the method of choice, except perhaps in deep cavitary wounds.23
Taking the "free-range" concept a step further, Morrison21 and Bras24 described a technique for
MDT in deep puncture wounds to the solar surface of the foot that involved the navicular bursa
and adjacent structures. A ¼-in (6-mm) Penrose drain is threaded up through the wound tract
from the solar surface of the foot, along the palmar/plantar aspect of the deep digital flexor
tendon, and out to the skin through a stab incision at the back of the pastern. The maggots are
applied to the wound on the solar surface of the foot and permitted to migrate up and down the
drain tract. After 10–14 days, the drain is removed and any remaining maggots flushed from the
tract. In this way, debridement of necrotic tissue deep within the wound is achieved with
minimal surgical dissection.
Wound management during MDT
Depending on the wound, the dressings are changed daily at first (more frequently for very
effusive wounds), taking care not to disturb the maggots in the process of removing the dressings
and inspecting the wound. Although the maggots may be in the wound for several days at a time,
it is important to monitor their progress and viability throughout.
When the injury requires the rigid support of a cast, MDT may still be used by cutting a small
window in the cast to allow access to the wound.21 Maggots may also be used under a hospital
plate for wounds on the solar surface of the foot.21,24,26 As long as the maggots have air and the
clinician has direct access to the wound, MDT may be used in conjunction with rigid support or
protection.
Duration of therapy
The supplier recommends removal of the maggots after about 48 hours,25 but in clinical reports,
medical maggots have remained viable and active in equine wounds for 4 days23 and up to 7
days.21,24 As long as the maggots are continuing to debride the wound and the patient is
tolerating their presence (see below), it may be a reasonable balance of economy and efficacy to
leave the maggots in the wound until most have stopped feeding (typically, 4–7 days after
hatching).
Whether or not a further round of MDT is needed depends on the progress of wound
debridement, disinfection, and repair. The recommendation is to continue MDT until all necrotic
tissue is debrided and the wound bed comprises healthy granulation tissue.21,24 With deep
puncture wounds, clinical response may also include the patient's comfort and the persistent
exodus of larvae from the wound (indicating that the larvae have finished feeding).21 When
another round of MDT is needed, the fresh batch of maggots may be applied to the wound either
immediately after the previous batch is removed or a few days later and after further light
surgical debridement.23
In the case series reported by Lepage et al. involving 41 horses and donkeys with a variety of
chronic/infected wounds, 36 patients (88%) required only 1 round of MDT (lasting an average of
3 days). Five patients (12%) required a second round (another 3 days of MDT), but none needed
more than 2 rounds, including the foal with MRSA infection associated with fracture repair.23
Wound age ranged from 2 days to >2 months, so their case series is a good representation of the
types of difficult wounds commonly seen in equine practice. As a point of comparison, MDT in
human medicine is often used for chronic, nonhealing wounds in systemically compromised
patients, and wound debridement may take at least 6 rounds of MDT.10,25
Concurrent treatment
Maggot debridement therapy is not intended to be a stand-alone procedure, although in some
wounds it may be used as the primary means of debridement.21 In wound infections involving
bone, it is important to continue or institute other treatments as appropriate, such as these:
local/regional and systemic antibiotic therapy
pain management
tetanus prophylaxis
rigid support of the injured area (e.g., internal/external surgical fixation, cast, splint,
Robert Jones bandage)
therapeutic shoeing (hospital plate, raised-heel shoe, etc.)
endoscopic lavage and debridement for concurrent synovial infections
stall confinement ± controlled activity (taking care to avoid dislodging the maggots)
physical therapy
There is limited evidence that MDT may also be used in conjunction with hyperbaric oxygen
therapy, as long as the larvae are not too immature.29
An intriguing aspect of MDT that warrants further study is that, although the various effects on
wound debridement, disinfection, and healing are associated with the presence of the maggots
and/or their secretions in the wound, these benefits may persist for up to 3 weeks after the
conclusion of MDT.10 For example, Sherman et al. conducted a small case-matched clinical
study of human patients with very chronic, nonhealing wounds (pressure or ischemic ulcer,
postoperative infection, etc.) and serious comorbidities (paraplegia, diabetes, cardiac or
peripheral vascular disease, etc.). Presurgical MDT (n=10 wounds) was compared with
conventional wound debridement (control; n=19 wounds) in preparation for delayed primary
closure, skin grafting, or skin-flap reconstruction. Even when surgical repair was performed 2–3
weeks after MDT, the wounds that underwent presurgical MDT all healed without postoperative
infection or dehiscence, whereas 6 of the control wounds (32%) developed postoperative
infections.30
What to Expect
A reddish-brown exudate is often produced by wounds undergoing MDT and is considered
evidence of effective debridement.21,23 In most published equine cases, the use of MDT avoided
the need for further surgical debridement, and in those that required further debridement, only
light surgical debridement was needed.21,23,24
Adverse effects in equine patients are uncommon and relatively mild, consisting primarily of
irritation or discomfort (e.g., stamping or rubbing the treated limb).21-23 This type of mild
irritation or itchiness is also reported in human patients during MDT and is attributed to the
movement of maggots in the wound bed.10 In the case series by Lepage et al., 7 patients (17%)
showed some signs of discomfort 24–36 hours after the maggots were applied,23 which is
consistent with the timing in human patients reporting this sensation.10
Pain or an increase in the level of existing pain is occasionally reported in human patients during
MDT,30,31 but this effect, identified by the patient specifically as pain, has not been reported in
horses. Either it is very uncommon in the types of equine wounds treated with MDT or it is
clinically indistinguishable from the irritation caused by larval activity. In human patients
experiencing pain during MDT, analgesic medications are usually effective, allowing MDT to
continue. When the pain cannot be controlled, MDT must be terminated.10,31
Hyperammonemia attributed to extensive tissue breakdown is described in severely fly-blown
livestock and it has been reported during MDT in a human patient with chronic lymphedema.32
However, this complication has not been reported with MDT in horses.
Current Directions in Maggot Research
The present and future of medical maggot research involves the isolation and either purification
or de novo synthesis of larval enzymes and antimicrobial peptides for use in wound dressings
and other topical wound treatments.9,10,20 There are also efforts underway to develop pathogen-
specific maggots or "microbe-stimulated maggots."33 This research is based on observations that
maggots removed from infected wounds undergoing MDT or experimentally stimulated by
pathogenic exposure (e.g., puncture by a needle dipped in lipopolysaccharide) produce greater
amounts of antibacterial substances than sterile maggots not yet exposed to an infected
wound.9,10 Not only might this research result in medical maggots that are at peak antimicrobial
potency immediately upon application, it may also yield new antimicrobial substances for the
treatment of infections caused by multidrug-resistant pathogens.
VACUUM-ASSISTED CLOSURE
Vacuum-assisted closure (VAC) is also known as negative-pressure wound therapy (NPWT).
One VAC device company has registered the acronym, V.A.C.®, so to avoid legal issues, the
technique is increasingly referred to as NPWT in the scientific literature and in product
materials. However, in practice this method of wound care is still usually—and legitimately—
referred to as VAC or VAC therapy, as it involves the generation of a vacuum over the wound
bed to assist in wound closure, and it can be achieved using a variety of equipment and supplies,
both proprietary and generic.
The current VAC methods were developed by a plastic surgeon and a bioengineer for use on
open fractures, chronic ulcers, and other large, open, infected or otherwise complex wounds that
are either not amenable or not responsive to conventional wound care.34,35 Vacuum-assisted
closure is now widely used in human medicine for a variety of acute and chronic wounds that are
traumatic, surgical, or ischemic in origin, including open thoracic and abdominal wounds, and
wound infections involving bone.36-42
In addition to being used as the principal mode of wound care to accelerate second-intention
wound healing, VAC therapy may also be used to prepare a wound for delayed primary closure
and to facilitate acceptance of skin grafts and flaps.37,38 Although use of VAC therapy in
veterinary medicine has lagged behind that in human medicine, numerous clinical studies have
been published in the past 15 years that document the successful use of VAC therapy in small
animals,43-54 wildlife,55-57 and horses.58-61
Mechanisms of VAC Therapy
The principle is simple: subatmospheric pressure (vacuum/suction) of between 75 and 125
mmHg is applied to the wound, either continuously or intermittently, using the following
equipment:34,35
open-cell foam (sponge) dressing, selected or cut to fit the dimensions of the wound and
applied to the wound bed
occlusive drape, applied over the wound dressing and firmly adhered to the skin
surrounding the wound to form an airtight seal over the wound
small vacuum pump that draws exudate from the wound to a collection canister via
tubing seated in/on the wound dressing
Some of the newer VAC systems also allow instillation of sterile saline, antiseptic, or antibiotic
solutions to the wound bed in conjunction with VAC therapy (e.g., cycles of infusion–soak–
aspiration) for severely contaminated or chronically infected wounds.41,62
Experimental and clinical studies indicate that VAC therapy has several benefits in the treatment
of infected wounds:34,35
evacuates wound exudate, which moderates the inflammatory response in the wound bed
and reduces edema in and around the wound
removes bacteria from the wound, including multidrug-resistant strains such as
MRSA39,41
improves microcirculation and thus tissue perfusion within the wound bed
disrupts bacterial biofilm formation and maturation (see below)
prevents further contamination by keeping the wound covered
speeds wound closure
§ limits the retraction phase in acute wounds by mechanically drawing the wound edges
closer together58
§ facilitates the contraction phase by the same means
§ upregulates the expression of a variety of cytokines and growth factors involved in
granulation and epithelialization
§ protects the wound bed from desiccation and maceration
Specifically with wound infections involving bone, VAC therapy is documented to speed
granulation tissue coverage of exposed bone and orthopedic implants in humans37-39,42 and
animals.43,46,49,53 Surgical debridement is still required, but addition of VAC therapy can greatly
facilitate infection control and wound healing in these cases.
Antibiofilm properties
Vacuum-assisted closure is not primarily an antibiofilm strategy, but it does facilitate the control
and removal of bacterial biofilms in at least 2 ways:
continuous removal of unattached bacteria, suspended within the evacuated fluid, inhibits
biofilm formation in acute or freshly debrided wounds
the periodic dressing changes (typically, every 2–3 days) repeatedly disrupt or remove
mature biofilms that may have formed on the wound surfaces
The most commonly used VAC dressings are open-pore, polyurethane foam pads or sponges, cut
to fit the wound dimensions. Even with due care, dressing changes disrupt the surface of the
wound bed to some extent. The foam dressings are designed to stimulate granulation, and even
after only 48 hours of VAC use, some granulation tissue will have extended into the surface of
the foam dressing material.34,35,58 In biofilm-infected wounds, this disruption can be an
advantage,52 as bacterial biofilms are quite resistant to chemical damage but are vulnerable to
mechanical damage. Once the biofilm substance is disrupted, host defenses and antibiotic drugs
can more effectively destroy the bacteria within.
The VAC systems that allow for the instillation of antiseptic or antibiotic solutions into the
wound represent a third possible mechanism by which VAC therapy may have antibiofilm
properties.41,62 However, most VAC systems in current use simply provide continuous or
intermittent evacuation of fluid from the wound. Any local application of antimicrobial
substances to the wound must be done during a dressing change or via an antibiotic-impregnated
depot material such as polymethylmethacrylate.63
Concurrent regional and/or systemic antibiotic therapy would, of course, deliver antibiotic drugs
to the wound bed and is advised in most cases of pre-existing or potential wound infection. In
fact, VAC therapy may improve antibiotic delivery to the wound surface by increasing wound
microcirculation, particularly in wounds complicated by poor perfusion.
A recent experimental study in healthy dogs with surgically-created, full-thickness skin wounds
measured the concentrations of cefazolin in the wound tissues following IV administration and
found that drug concentrations were not significantly different between wounds treated with
NPWT and those treated with conventional nonstick dressings.64 However, in a small clinical
study of human patients with skin ulcers or other naturally occurring wounds involving exposed
muscle, fascia, or adipose tissue, NPWT resulted in vancomycin concentrations in the wound
exudate that were 67% of the serum vancomycin concentration following IV administration,
which is higher than previously reported in soft tissues not treated with NPWT.65
In a recent case report, VAC therapy was instrumental in resolving chronic, nonhealing, biofilm-
infected wounds on the elbows of a 4-year-old Mastiff which had resulted from attempts to
excise hypertrophic calluses. Bacterial biofilms were identified histologically in tissue samples
from both wounds, and polymicrobial infection including Staphylococcus intermedius, S.
epidermidis, and Streptococcus canis was confirmed on culture and pyrosequencing. A
combination of surgical debridement, systemic antibiotic therapy, pressure relief over the
elbows, and VAC therapy (applied for 6 days) prevented biofilm re-formation and allowed the
wounds to heal following primary closure in one wound and skin-flap reconstruction in the
other.52
Clinical limitations
It is advised that VAC not be applied directly over an exposed blood vessel, anastomosis,
internal organ, or nerve (although it can be used if the vessel or organ is protected in some way),
nor used in patients with bleeding disorders. Its use in patients with wounds complicated by
malignancy, untreated osteomyelitis, unexplored fistulae, or necrotic tissue with eschar
formation is advised only after appropriate surgical excision or debridement.62 As mentioned
above, VAC therapy can be used on wounds with exposed bone or orthopedic implants, but
surgical debridement of infected soft tissues and bone, and removal of failed implants, may still
be required.
One human case report posed the question of whether VAC therapy may encourage the growth
of anaerobic bacteria in the wound (in that case, Helcococcus kunzii), given that the occlusive
drape forms an airtight seal over the wound.66 However, the question remained unanswered in
that case, and two decades of clinical use in contaminated and infected wounds would suggest
that this complication, if possible, is rare. Even so, it is advised that the wound dressings and the
occlusive drape used to maintain an airtight seal over the wound be removed if the vacuum pump
is switched off for more than 2 hours.67
The duration of VAC therapy depends on the rate of wound healing and on the goals of treatment
(facilitate second-intention healing, prepare the wound for delayed primary closure or skin
grafting/reconstruction, etc.). Continued use of VAC therapy beyond the point at which healthy
granulation tissue fills the defect may impede wound repair. For example, in an experimental
study of healthy dogs, small (8 cm sq) full-thickness skin wounds were surgically created on
each antebrachium.68 The wounds were then treated with either NPWT or conventional wound
dressings (control wounds) for 21 days. Compared with the control wounds, granulation tissue
appeared significantly earlier and was smoother and less exuberant in the wounds treated with
NPWT. However, wound contraction and epithelialization were less after Day 7 in the NPWT-
treated wounds than in the control wounds.
VAC Therapy in Equine Wounds
Published reports on the use of VAC therapy in horses are sparse yet positive. Vacuum-assisted
closure has been used with success in horses the following circumstances:
acute or subacute wounds with extensive soft tissue deficits not amenable to primary or
delayed primary closure58,69
chronic wounds over joints or bone (e.g., tarsus, carpus, third metacarpus/tarsus,
lumbosacral spine)61,70,71
grossly contaminated or infected wounds60,61,69
to prepare a wound bed for skin grafting or reconstruction and/or facilitate skin graft or
flap acceptance59-61,70,71
Wounds involving bone in small animals
To date, there are no reports in English that described the use of VAC therapy in horses with
osteomyelitis. However, VAC therapy has been used with success in dogs and cats with serious
wound infections involving bone, including wounds that exposed orthopedic implants.43,46,53
Kirkby et al. described their experiences with VAC therapy in small animals at the University of
Florida. In discussing cases of surgical dehiscence, often associated with wound infection and
resulting in exposed orthopedic implants, they stated that "VAC therapy has been instrumental in
accelerating the development of healthy granulation tissue and the rate of contraction, resulting
in a decreased time to wound closure."46
The following canine case, reported by Bertran et al., illustrates the utility of VAC therapy in
such wounds. An 8-month-old Labrador Retriever sustained a grade IIIb open shearing injury to
the left tarsus. (Grade IIIb fractures are open fractures with extensive soft tissue damage or loss
and periosteal stripping with underlying bone damage; they are usually associated with gross
contamination.) Two days after tarsal arthrodesis, severe infection developed at the surgical site
and resulted in wound dehiscence which left an extensive soft tissue defect and exposed metal
implants. Owing to the nature and location of the injury, VAC therapy was used as part of the
treatment approach. By Day 10 of VAC therapy, healthy granulation tissue covered most of the
defect, and by Day 12 VAC therapy could be discontinued. The wound continued to heal by
second intention and no surgical revision was necessary.49
There are similar anecdotal reports of infection control, rapid coverage with healthy granulation
tissue, and good functional outcomes in canine patients with exposed and damaged bone
following traumatic or surgical wounds, with or without exposed surgical implants. In some
cases, the wound was left to heal by second intention at the conclusion of VAC therapy (wound
care continuing with conventional dressings),72 and in other cases VAC therapy prepared the
wound for either delayed primary closure73,74 or skin grafting/flap reconstruction.75,76
Sources and Doses
Numerous companies now offer NPWT systems or devices in the US. The human devices and
supplies (dressings, drapes, tubing, canisters, etc.) are readily adapted to use in animals. In fact,
most of the published reports on VAC therapy in horses have used the human devices and
supplies.58-61 That said, Kinetic Concepts, Inc. (KCI) now has a veterinary arm, KCI Animal
Health, which offers veterinarians training in applying VAC therapy that is specific to small or
large animal patients.
Regardless of which company and VAC system is chosen, the important components are these:
vacuum pump that delivers negative pressure at -125 mmHg; subjectively, this pressure is
effective and well tolerated in horses,58-61,69-71 so pumps that offer variable pressure
settings from -75 mmHg to -200 mmHg may be more than is required
vacuum pump that allows continuous delivery of negative pressure; the continuous mode
was used in all of the published equine case reports, and anecdotally it may be of more
benefit and better tolerated than the intermittent mode in most equine wounds
collection canister that holds at least 300 mls of wound exudate (see below)
portable pump that can be attached to the horse's body, allowing the patient to move
freely in the stall and lie down without interrupting VAC therapy
In the equine case reports to date, the overall duration of VAC therapy was anywhere from 5
days to 38 days,58-61,69-71 so using a system that allows the horse to move about in the stall and
rest lying down is important for patient comfort and client acceptance when prolonged therapy is
required. Tying the horse so that it cannot lie down during therapy may be tolerated for relatively
short periods,59-61 but another option in the absence of a portable pump is to use coiled tubing
(e.g., large animal IV extension set) with the vacuum pump suspended above the stall on a
swivel hook so that the horse can move around in the stall and lie down without disrupting the
vacuum.58 More recent anecdotal reports illustrated using a portable pump attached to the horse's
body with a surcingle.69,70 Disruption of the tubing, and thus loss of the vacuum, is less likely
with on-board pumps than when the pump is attached to the stall wall or an overhead beam.
The KCI pump recommended for use in horsesb satisfies all of the above criteria, including
portability, but one limitation of its present design is that the canister holds only 300 mls and is
not reusable, so if it fills during the course of VAC therapy, it must be replaced. Lazzaretti
reported on a series of 7 horses with wounds of various types that were treated with VAC
therapy.61 The median amount of fluid aspirated during VAC therapy was 567 ml (range, 300–
800 ml), and mean exudate volume in the first 24 hours of VAC therapy was 159 ml (range,
100–200 ml). These volumes are consistent with other equine reports,60 and even less than
some.58,59 For example, Gemeinhardt and Molnar described having to empty the 1-liter collection
flask every 10–12 hours during the first few days of VAC therapy for a pair of large neck
wounds on a horse.58
As veterinary demand for VAC therapy increases, we will likely see an increase in the number of
companies actively marketing to veterinarians and consequently developments in product design
that account for such species differences as the volume and character of wound exudate between
small and large animal patients, as well as longer battery life and more reusable components.
Applying VAC Therapy
The key to effective VAC therapy is to create and maintain an airtight seal over the wound so
that the vacuum can be maintained for the duration of therapy:58,61,67
1. Clip the hair around the wound to create a hairless margin of 2–3 inches (5–7.5 cm), and up
to 4 inches (10 cm) if the contours of the area might make it difficult to achieve an airtight
seal with the occlusive drape.
a. Use a sharp, fine clipper blade (e.g., #40), as for surgical preparation. Stubble can prevent
an airtight seal from being created, and hair regrowth can cause premature loss of the seal
between dressing changes.
b. The skin may also be shaved, but it is important to avoid creating razor burns or nicks, as
active dermatitis interferes with adherence of the occlusive drape and thus the
creation/maintenance of an airtight seal.
c. Some authors described using a human depilatory cream (e.g., Nair™); however, these
creams caused irritation and serous discharge from the depilated skin which prevented
application of the adhesive drape for up to 24 hours and in some cases contributed to the
patient's discomfort at subsequent dressing removal.58,61 It appears from other reports that
chemical depilation is not necessary, as long as fine clippers are used to thoroughly
remove the hair and alcohol is used to degrease the skin (step 3).
d. When clipping/shaving the skin around the wound, take care to prevent hair from falling
into the wound.
2. Debride and irrigate the wound, if necessary, to remove gross contamination, necrotic tissue,
and wound exudate. In chronic wounds, any exuberant granulation tissue should also be
excised.
3. Thoroughly clean the surrounding skin with surgical scrub and finish with alcohol to ensure
that the skin is thoroughly degreased before the adhesive drape is applied. Allow the skin to
air dry completely.
4. Cut the VAC wound dressing (open-cell polyurethane foam or similar) to the dimensions of
the wound and gently pack into the wound so that the dressing is in contact with the entire
wound surface but does not overlie the surrounding skin.
a. For deep or large wounds needing multiple pieces of dressing, make note of the number
of pieces of dressing used to ensure that all are removed at the next dressing change.
5. Apply a medical adhesive to the hairless skin around the wound; cover the area generously,
then allow the adhesive to dry just to the point of being slightly tacky to the touch.
a. A recommended combination for equine skin is compound tincture of benzoin (CTB,
Friar's Balsam) plus a thin strip of livestock ID tag cementc on the skin just adjacent to
the wound.67
b. Medical adhesive sprayd may also be used either alone or in combination with CTB.
6. Apply the occlusive drape over the wound and press it firmly to the prepared skin around the
entire perimeter of the wound to create an airtight seal.
a. Options include V.A.C.® Drape,e other proprietary NPWT drape, or simply a surgical
adhesive drape (e.g., Steri-Drape™)f; antimicrobial drapes such as Ioban™ are
unnecessary and may increase the likelihood of skin irritation.
b. If necessary, cut the drape to size before application or trim any of the drape that extends
beyond the clipped area after application. Loose or unattached drape contributes to
premature loss of the airtight seal.
c. Smooth out any creases in the drape, and if necessary apply a second piece of adhesive
drape over the edge of the primary drape in any suspect area.
d. Note: If using plain tubing (e.g., repurposed IV extension tubing) to connect the wound
dressing to the pump instead of proprietary tubing (see below), seat the end of the tubing
on or in the wound dressing before applying the occlusive drape. After applying the
drape, make sure to pinch it up and press it around the tubing at the wound margin to
ensure that a complete airtight seal is formed over the entire perimeter of the wound,
while at the same time preventing the tubing from lying directly against the skin (and
potentially causing pressure necrosis).58
7. Attach the tubing that connects vacuum pump to wound dressing.
a. If using the KCI tubing system,g follow the instructions for applying the sensor pad (cut a
1-inch diameter hole in the occlusive drape over the center of the dressing and apply the
pad directly over the hole).67
b. If using a different system, follow the instructions for that system.
8. Connect the tubing to the pump and switch on the vacuum (-125 mmHg, continuous mode).
a. If an airtight seal has been created over the wound, the wound dressing immediately
begins to compress down onto the wound bed.
b. If the wound dressing does not immediately become compressed, check the system for air
leaks between dressing and pump. If the tubing has a clip or clamp, check to make sure
that the clip/clamp is open.
9. Attach the pump to the horse's body using a surcingle or bandage, as appropriate. This step
may instead be performed at the start of the procedure.
10. If necessary, apply a firm bandage over the occlusive drape to limit movement at the site and
prevent the horse from disturbing the wound.
a. The sensation of the vacuum when it is first applied may cause the horse to nuzzle the
site, lift the limb, or otherwise disrupt the seal.
b. If necessary, use a neck cradle to prevent the horse from disturbing the wound dressings.
c. A modified Robert Jones bandage or thick leg wrap may be advisable when using VAC
therapy over a high-motion joint such as the carpus/tarsus or fetlock. These sites also
have anatomical contours that make an airtight seal difficult to achieve and maintain.
For the duration of VAC therapy, confine the horse to a stall with clean, dry bedding and monitor
the VAC system closely. The portable pumps designed for ambulatory human patients and now
recommended for veterinary patients are not intended for use at any gait faster than a slow walk.
In horses, the biggest challenge with VAC therapy is maintenance of an airtight seal over the
wound, and excessive movement is one of the most common reasons the seal is lost during
treatment. Although portable pumps that can be attached to the horse's body are a great leap
forward in VAC therapy for veterinary use, they do not mean that the horse can be turned out in
any area larger than the average stall.
Dressing changes
Except when using VAC therapy to support newly grafted skin, it is recommended that VAC
dressings be changed every 2–3 days.67 They can certainly be changed earlier; the only downside
is the added expense of extra dressings, drapes, and tubing. However, if the dressing is left on an
open wound for longer than about 72 hours, the dressing changes become increasingly more
disruptive to the wound bed and uncomfortable for the patient, as granulation tissue becomes
invested in the dressing material.
If the dressing is adhered to the wound, it may help to soak the dressing in sterile saline for 15–
30 minutes before carefully removing it.67 Some horses require light sedation for dressing
changes, but most do not if the dressing is changed within 3 days of application.58-61
Duration of therapy
Typically, open wounds have begun to granulate by the time of the first dressing change (usually
2–3 days after application). How long VAC therapy is continued thereafter depends on the
treatment goals. Large wounds with substantial tissue loss that are expected to heal by second
intention may need a total of 4–6 weeks of VAC therapy before the defect is filled with healthy
granulation tissue and epithelialization is well underway.58,69 If the wound is to undergo skin
grafting or flap reconstruction, granulation may be sufficient in 5–6 days (i.e., by the second
dressing change).70,71
Concurrent treatment
As for maggot debridement therapy, concurrent treatment must be continued or instituted as
appropriate for the case, particularly systemic antibiotic therapy, tetanus prophylaxis, and pain
management. There are not yet any reports on the concurrent use of VAC therapy and local or
regional antibiotic delivery in horses. However, for deep bone infections, either antibiotic-
impregnated depot materials or RLP with antibiotics may be advisable and may work
synergistically with VAC therapy.
What to Expect
In most wounds, the exudate is serous in character, although with fresh or recently debrided
wounds it may be serosanguineous for the first couple of days. The volume of wound exudate
typically is greatest in the first few days of VAC therapy and often exceeds 100 ml/day
initially.58-61 Thereafter, the volume decreases and the exudate usually becomes more viscous. In
addition to the appearance of the wound bed at each dressing change, the volume and character
of the wound exudate may be used to decide when to discontinue VAC therapy. When there is
little exudate ( 30 ml) collected in a day (and the system is functioning properly), it is probably
time to conclude VAC therapy.
Most horses tolerate VAC therapy well, although protective bandages or neck cradles may be
needed for some wounds and some horses. Adverse effects are minor and have consisted
primarily of mild irritation of the skin surrounding the wound, mild discomfort and/or bleeding
from the surface of the granulation bed during dressing changes, and occasionally mild
discomfort when the vacuum pump is first switched on.58-61 In only a few patients (typically,
young or highly strung individuals) has the horse not tolerated the procedure.59,61
Current Directions in VAC Research
One of the current trends in human VAC therapy is the development of ultraportable systems for
ongoing wound care in ambulatory patients. In addition to battery-powered, single-use,
disposable units weighing less than 12 oz. (320 g), there is a mechanically powered NPWT unit
that uses a spring-loaded cartridge to generate negative pressure in the wound.77 Whether
electrically or mechanically powered, these small, ultralight units necessarily have small
collection canisters ( 250 ml), so they are suitable for use only on small wounds with low
exudate production. Their utility in equine practice therefore is likely to be fairly limited.
Another trend in VAC research is the combination of regenerative medicine and VAC therapy.
For example, in a small clinical study involving 4 human patients with nonresponsive wounds
that exposed bone, activated protein C was used in conjunction with VAC therapy. All 4 patients
showed rapid granulation tissue production and a marked reduction in wound size and depth
within the first week of treatment. Long-term follow-up suggested that this combination
treatment prevented osteomyelitis.37
The concurrent use of fat grafts is another approach that has shown promise experimentally. In
an in vivo study, full-thickness skin wounds with denuded bone were surgically created in rats.
Granulation over the exposed bone was greater for those treated with a combination of fat grafts
and VAC therapy than with either treatment alone. The authors described this approach as a
synergistic interaction of regenerative cells, hospitable wound matrix, and stimulating
micromechanical forces. Interestingly, fat grafting alone (no VAC therapy) resulted in complete
necrosis.78
Use of VAC therapy also promotes the vascularization of bone grafts. In an experimental study
using rabbits, allogeneic bone grafts were surgically placed in the proximal femur and the
wounds treated with either VAC therapy or conventional wound closure. At 4, 8, and 12 weeks
after bone grafting, the callus was larger, contained more calcium, and expressed greater
amounts of fibroblast growth factor-2 in the VAC-treated group than in the control group.79
ANTIBIOTIC-IMPREGNATED DEPOT MATERIALS
In addition to surgical debridement and appropriate wound care, achieving locally high
concentrations of the chosen antibiotic(s) is important with serious infections involving bone,
such as osteomyelitis secondary to open fracture repair. Maintaining therapeutic drug
concentrations for several days or weeks is also important, particularly in chronic osteomyelitis,
where treatment may be complicated by the presence of bacterial biofilm. Here, antibiotic-
impregnated materials that are deposited in or adjacent to the bone defect can be crucial to a
good outcome, as they act as on-the-spot, sustained-release vehicles for the antibiotic drug(s).
The most common depot material used for local antibiotic delivery in horses, and the current
standard in human orthopedic surgery,80 is polymethylmethacrylate (PMMA), or bone cement.
Use of antibiotic-impregnated PMMA beads is well documented for the treatment of serious
wound infections in horses, particularly those involving bone.6,81-84 It is also used in the
prevention of postoperative orthopedic infections in horses. Although, in a series of 192 horses
and foals undergoing internal fixation for repair of long bone fractures or for arthrodesis, use of
antibiotic-impregnated PMMA at surgery did not significantly improve the rates of postoperative
infection or hospital discharge.85
Bioabsorbable Depot Materials
Antibiotic-impregnated PMMA beads may release therapeutic concentrations of the drug for
several weeks, but the beads are not biodegradable, so they may require removal once the
infection is resolved. Current trends in the evolution of antibiotic-impregnated depot materials in
human medicine are toward biodegradable or bioabsorbable materials that provide sustained
antibiotic release, do not require subsequent removal, and may also serve as a scaffold for bone
repair. Antibiotic-loaded "bone void fillers" under study or currently in clinical use include these:
plaster of Paris (POP) or calcium sulfate hemihydrate80
ground bone86 or hydroxyapatite80,87
composites such as hydroxyapatite-POP-chitosan88
various polymers of lactic acid and/or glycolic acid89,90
gelatin sponges combined with β-tricalcium phospate91
gentamicin-impregnated collagen sponges92-94
Plaster of Paris
Antibiotic-impregnated POP has been used in horses to treat orthopedic infections and to prevent
alveolar infection and osteomyelitis after dental extraction.6,95 Plaster of Paris is biocompatible,
biodegradable/absorbable, readily available, and inexpensive. Furthermore, the elution
characteristics of gentamicin-POP beads suggest that they may be useful in the treatment and
prevention of osteomyelitis caused by gentamicin-sensitive bacteria.
In an in vitro study, beads premade from 20 grams of POP powder, 5 ml (500 mg) of gentamicin
solution, and 3 ml of phosphate buffered saline were incubated in porcine serum at 37° C for 14
days, during which the serum gentamicin concentration and antibacterial activity against an
equine E. coli isolate were periodically evaluated. The beads released gentamicin for the entire
14-day sampling period and the resulting serum inhibited E. coli growth at all time points.96
However, it is worth noting that 80% of the gentamicin was released in the first 48 hours of
incubation,96 so gentamicin-POP beads may be more suited to the treatment of acute than chronic
bone infections, and to the prevention of osteomyelitis in contaminated wounds involving bone.
These findings and conclusions are consistent with an earlier study which showed rapid elution
of various antibiotic drugs from POP, followed by a sustained but gradually diminishing rate of
drug release.97
In another in vitro study, the elution characteristics of gentamicin (50 mg/g) from POP beads
were compared with those from PMMA beads and from POP beads coated in porcine small
intestinal submucosa (an extracellular matrix material). Coating the POP beads in this way
slowed the release of gentamicin and increased the total amount of drug released compared with
uncoated POP beads and with PMMA beads. Gentamicin concentrations in the eluent remained
at 1 µg/ml for the duration of the 42-day study period in the coated POP beads.98
The in vitro elution characteristics of other antibiotics in POP suggest that therapeutic
concentrations of aminoglycosides and glycopeptides (e.g., vancomycin) may be expected for up
to 3 weeks, but cephalosporins and penicillins for only 2–3 days; and quinolone beads may be
too brittle for clinical use.99 Clinically, the following antibiotic drugs and doses have been
combined with POP for use as alveolar packing after cheek tooth removal in horses: cefazolin, 1
gram; sodium ampicillin-sulbactam, 1.5 grams (1 g ampicillin, 0.5 g sulbactam); trimethoprim-
sulfonamide, 2 grams; metronidazole, 1 gram.95
In that study, approximately 40 grams of POP were combined with 12 ml of saline and the
chosen antibiotic drug. After mixing and setting aside, the antibiotic-impregnated POP reached a
good working consistency ("dough ball") in 10–15 minutes, at which time it was molded to fit
the alveolus (filling only the gingival half of the socket depth). The POP packing hardened in
situ in 30–35 minutes.95 A similar process could be used in clinical practice for deep wounds
involving bone.
Gentamicin-collagen sponges
As discussed in the second article of this series,2 gentamicin-impregnated collagen sponges have
been used in Europe for the treatment of synovial infections in horses and cattle for several
years,92,100,101 and they may soon be available in the US. However, this material may not be as
well suited to the treatment of deep bone infections, as locally high concentrations of gentamicin
are not likely to be sustained for more than a few days.102
That said, gentamicin-collagen sponges are used, along with systemic antibiotic therapy, for the
prevention of osteomyelitis in human patients undergoing high-risk surgical procedures,
including cardiac surgery via sternotomy94 and internal fixation of open fractures.93 In support of
this approach, a study using a rat model of S. aureus-induced osteomyelitis found that a
combination of gentamicin-collagen sponges and systemic cefazolin more effectively reduced
bacterial numbers in the infected bone than either systemic cefazolin or locally implanted
gentamicin-PMMA beads alone.103
It seems that antibiotic-POP beads and gentamicin-collagen sponges offer similar advantages—
rapid release of the loaded antibiotic, resulting in locally high antibiotic concentrations, in a
biodegradable/absorbable form—and suffer from similar limitations—substantial drop in local
antibiotic concentrations after 48 hours. They may therefore benefit from the same solution:
combine their highly effective yet short-lived local drug delivery with a more sustained systemic
or regional antibiotic regimen.
REGIONAL ANTIBIOTIC DELIVERY
Regional limb perfusion with antibiotic drugs has become a routine component of management
for serious infections at or below the carpus/tarsus in horses. Both intravenous (IV) and
intraosseous/intramedullary (IO) routes are well described.6,104-107 One recent variation on the
theme is use of the cephalic or saphenous vein instead of a more distal vein for IV-RLP of the
lower limb.
Regional Limb Perfusion via Cephalic/Saphenous Vein
Kelmer et al. have described a technique for repeated IV-RLP via the cephalic or saphenous
vein.106,108,109 By maintaining an indwelling IV catheter in one of these proximal veins, RLP can
be repeated daily if necessary, and for as long as clinically indicated. This approach has some
advantages over the current standard technique which uses a palmar or plantar vein:
catheter placement is easier in the larger and more stable cephalic/saphenous vein than in
a palmar/plantar vein (particularly a digital vein)
catheter maintenance for repeated IV-RLP likewise is easier in these more proximal veins
catheterization is usually possible even when cellulitis, edema, or the location of the
wound prevents catheter placement nearer the site of infection
repeated IV-RLP may be performed even when the injury requires immobilization in a
cast or Robert Jones bandage
On the downside, safely placing a catheter in the saphenous vein can be a challenge in some
horses. In addition, larger volumes of perfusate and higher antibiotic drug doses are needed for
perfusion of the distal limb via these more proximal veins (see below).
Equipment and technique
In the technique described by Kelmer et al.,108 an over-the-wire polyurethane catheter (16 ga, 15
cm)h is recommended for long-term use, although an over-the-needle polytetrafluoroethylene
catheter (20 ga, 4 cm)i may be used instead. The catheter is placed either while the horse is under
general anesthesia for wound debridement or fracture fixation, or while the horse is standing,
under sedation and local anesthesia. The procedure is essentially the same as placement of an
indwelling jugular catheter, and as with any indwelling IV catheter, flushing the line with
heparinized saline every 4–6 hours helps ensure continued patency.
Just before perfusing the limb, a tourniquet is placed proximal to the catheter, as described for
RLP at more distal sites. In heavily muscled horses, it may be necessary to place a pad of gauze
(e.g., a small stack of "4x4s" folded in half) between the vein and the tourniquet to ensure that
venous outflow is fully occluded by the tourniquet. If the infection is localized to the carpus or
tarsus, a second tourniquet can be placed distal to the site; otherwise, only the proximal
tourniquet is used and the entire limb distal to the catheter is perfused. Once the antibiotic drug is
injected through the catheter, the tourniquet is left in place for 30 minutes and then removed.
This procedure is repeated each time RLP is performed.
If perfusing just the carpus or tarsus, the perfusion volumes and antibiotic drug doses routinely
used for RLP at a more distal site may be used. However, when perfusing the entire limb distal to
the cephalic/saphenous catheter, larger perfusion volumes and drug doses are needed. Typically,
the perfusion volume is 100 ml for adult horses and 50 ml for foals. Drug doses described for
RLP via the cephalic/saphenous vein are as follows:108
amikacin: 2 g
ceftiofur or cefoxitine: 1 g
chloramphenicol: 1 g
enrofloxacin: 1 g
imipenem*: 500 mg
ticarcillin: 1.7 g
vancomycin*: 1 g
*Reserve these drugs for documented multidrug-resistant pathogens that are shown to be
sensitive to the drug.
Although clinical and experimental studies of this technique are still limited, we may assume that
other antibiotic drugs which are safely and effectively used for RLP at more distal sites may also
be used via the cephalic/saphenous vein, the dose scaled accordingly for the larger perfusion
volume.
What to expect
In a series of 44 horses (45 limbs) with synovial injury/infection involving the distal limb,
Kelmer et al. performed RLP via the cephalic/saphenous vein daily for a median of 7 days
(range, 3–21 days).108 In most cases, the indwelling catheter and daily RLP were well tolerated,
the catheter was removed because the infection was resolved to the point of not requiring any
further RLP, and the catheter was still functioning well at removal. Catheter-related
complications were reported in 12 limbs (27%), phlebitis being the most common problem (11
limbs). In 1 limb, the catheter became dislodged and needed to be replaced.
Overall, the infection was resolved in 87% of the affected limbs, although concurrent
osteomyelitis was significantly associated with a poor outcome.108 In the 6 horses in which
treatment failed to resolve the infection, 4 horses had concurrent osteomyelitis involving the
synovial structure. Bone infection was not the focus of that study, but this small number of
patients with concurrent osteomyelitis illustrates an essential point about wounds with
established bone infections: achieving locally high antibiotic concentrations at the site of
infection is critical to success with deep bone infections, but it is only one component of an
effective treatment strategy. Surgical debridement is still required, along with sustained
antibiotic therapy, whether local, regional, systemic, or a combination of routes.
UNUSUAL PATHOGENS
Finally, several clinical reports over the past 15 years serve as reminders of the importance of
culturing both the soft tissues/wound exudate and damaged bone in serious wound infections
involving bone. We can make some generalizations for interim antibiotic therapy. For example,
traumatic wounds are likely to have polymicrobial infections with a mix of Gram-positive skin
commensals and Gram-negative enteric genera; and postoperative wound infections often culture
Staphylococcus spp. or Streptococcus spp.3 Based on these trends, a cephalosporin plus an
aminoglycoside is usually a good empiric choice. (Common bacterial wound pathogens and
reasonable empiric antibiotic selections for different types of wounds are discussed in the second
article of this series.2)
However, empiric antibiotic selection is not a good substitute for culture-guided antibiotic
therapy, particularly in severe or chronic infections. Laboratory analysis of wound specimens
should be performed in every case and include aerobic and anaerobic bacterial culture and
cytology. If the wound is not responding to treatment as expected, also consider fungal infection.
The following uncommon or unusual pathogens have been reported in associated with
osteomyelitis in horses: Actinomyces sp.,110 Aspergillus fumigatus,111 Blastomyces sp.,112
Candida sp.,113 Coccidioides immitis,114 Corynebacterium pseudotuberculosis,115 Cryptococcus
sp.,116 Rhodococcus equi,117,1 18 and Scedosporium prolificans.119 These reports remind us: never
assume!
CONCLUDING THOUGHTS
Wound infections that involve and invade bone can be very challenging cases, often requiring a
multifaceted approach and prolonged therapy for a good outcome. On the surface, there do not
appear to have been any great leaps forward in how we manage wounds of this type in horses.
However, a closer look reveals that there have been some remarkable advances in the past 15
years that are helping us tip the scales in favor of recovery, even though some of the techniques
described in this article are just beginning to pervade equine clinical practice.
It is somewhat ironic that at least 3 of the tools described here—medical maggots, vacuum-
assisted wound closure, and antibiotic-impregnated plaster of Paris—have their origins in the
dusty archives of medical history and are just now being revived or rediscovered. It may be
particularly ironic that "fly strike" now offers some of the best hope for the treatment of wound
infections caused by multidrug-resistant pathogens. It is a good reminder that not all creative
solutions to complex problems are to be found in the biotechnological future.
Author’s note: This article was written by me (Christine M. King) on commission in 2016 and published under
another person’s name. This article is some of my best work to date, yet it is credited to someone elsean
act of intellectual dishonesty, the ramifications of which I did not appreciate at the time. This article is
entirely my own original work, exactly as I submitted it. I retain the copyright.
************************
MANUFACTURERS' ADDRESSES
a Medical Maggots™, Monarch Labs, Irvine, CA; www.monarchlabs.com.
bV.A.C.Simplicity™, KCI® Animal Health, San Antonio, TX; www.kcianimalhealth.com.
cNasco's Anima ID Tag Cement, Nasco, Fort Atkinson, WI; www.enasco.com.
dHollister Medical Adhesive, Hollister, Inc., Libertyville, IL; www.hollister.com.
eV.A.C.® Drape, Kinetic Concepts, Inc., San Antonio, TX; www.kci1.com.
f Steri-Drape™, 3M™ Co., St. Paul, MN; www.3m.com.
gSensaT.R.A.C. Pad™, Kinetic Concepts, Inc., San Antonio, TX; www.kci1.com.
hMILACATH 2-Piece Guidewire Kit–16 ga x 15 cm [product #1606-2P], MILA International,
Erlanger, KY. www.milainternational.com.
iBecton, Dickinson and Company, Franklin Lakes, NJ.
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Antibiotics may fail to abolish an infection in synovial structures for several reasons: (1) inherent antibiotic resistance; (2) acquired antibiotic resistance; (3) inappropriate drug dosage, route or treatment duration; and (4) refugia. A strategy to include surgical debridement and ancillary treatments are discussed in eliminating infections of joints and other synovial structures.
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When managing serious wound infections in horses, it is important to consider the wound's entire ecology, including the source and extent of contamination, the presence of bacterial refugia (foreign bodies, surgical implants, devitalized tissue, inflammatory/necrotic debris, bacterial biofilms), the patient's immunocompetence, and tissue perfusion. In addition, the wound's pathogens and their antibiotic sensitivities must be identified. Culture-guided selection of antibiotic therapy and the use of local or regional modes of antibiotic delivery may be critical for success. By itself, antibiotic therapy may be insufficient to resolve bacterial infection in the presence of factors that contribute to the persistence or progression of infection and that otherwise delay wound healing.
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Background: Patients with composite bone non-union and soft tissue defects are difficult to treat. Vacuum-assisted closure (VAC) combined with open bone grafting is one of the most effective treatments at present. The aim of the present study was to preliminarily investigate the effect and mechanism of VAC combined with open bone grafting to promote rabbit bone graft vascularization, and to propose a theoretical basis for clinical work. Material/Methods: Twenty-four New Zealand white rabbits were randomly divided into an experimental and a control group. Allogeneic bones were grafted and banded with the proximal femur with a suture. The experimental group had VAC whereas the control group had normal wound closure. The bone vascularization rate was compared based on X-ray imaging, fluorescent bone labeling (labeled tetracycline hydrochloride and calcein), calcium content in the callus, and expression of fibroblast growth factor-2 (FGF-2) in bone allografts by Western blot analysis at the 4th, 8th, and 12th week after surgery. Results: At the 4th, 8th, and 12th week after surgery, the results of the tests demonstrated that the callus was larger, contained more calcium (p<0.05), and expressed FGF-2 at higher levels (p<0.05) in the experimental group than in the control group. Fluorescent bone labeling showed the distance between the two fluorescent ribbons was significantly shorter in the control group than in the experimental group at the 8th and 12th week after surgery. Conclusions: VAC combined with open bone grafting promoted rabbit bone graft vascularization.
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A 16-year-old horse was admitted to the clinic of the Department of Surgery and Anesthesiology of Domestic Animals of the Faculty of Veterinary Medicine (Ghent University) for the treatment of a very large, nonhealing wound extending over the dorsomedial and dorsolateral aspects of the left metatarsus. Surgical debridement of exuberant granulation tissue and new bone was performed under general anesthesia, followed by standard wound care under a bandage. Once a new bed of healthy granulation had formed, skin grafting was performed using the punch graft method. Due to the presence of a significant amount of wound exudate, cast immobilization was considered to be contraindicated. Instead, vacuum-assisted closure (VAC) therapy was used as a method of securing the skin grafts to the wound bed during the first days post-operatively. After five days of VAC therapy, the wound dressing was removed and an acceptance of nearly 100% of the punch grafts was observed. Complete epithelialization of the wound was evident 42 days after skin grafting. As far as the authors know, this is the first report describing the use of VAC therapy as a method of wound management in combination with punch grafting on the distal limb of a horse.