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190
R. Parwani
patient is in systemic sepsis [24]. The choice of
empirical antibiotics depends on the epidemiology of local pathogens most likely to be involved
and their antibiotic susceptibility properties. The
individual risk factors of the patient like existing
comorbidities, known allergies, other previously
isolated organisms, and their resistance proles
should all be considered. The empirical antibiotic
chosen should cover both Gram-positive cocci
and Gram-negative bacilli.
There is no clear consensus on the duration
of antibiotics and depends on the overall strategy decided by the multidisciplinary team. If
the antibiotics are being used as a part of suppressive therapy with implant retention, they
should be continued till the fracture consolidates. Intravenous antibiotics are recommended
till there are clinical signs of resolution of systemic septicemia, and healing of acute inammatory changes in the soft tissue. Oral
antibiotics can then be started [24]. By this
time, clear susceptibility and resistance proles
of the isolated organism are usually identied.
The strategy of using antibiotics only is unlikely
to eradicate infection and is likely to be suppressive only [25].
14.3.2 Debridement withor Without
Revision ofFixation
Debridement, as used in this discussion, means
the surgical exposure of the whole pathological
zone and the removal of all necrotic, contaminated, damaged, and/or infected tissue, whether
bone or soft tissue [26]. A good debridement is
usually required once an infection sets in after
fracture surgery. This is because of the presence
of a latent infection in bone and soft tissue.
Debridement should be thorough and start from
skin to bone. It should be planned properly,
keeping in mind the need for future reconstruction and salvage. A multidisciplinary team
adapted to the available resources, consisting of
an orthopedic surgeon, plastic surgeon, microbiologist, and infectious disease specialist,
should be constituted early [26]. The patient
should also be counseled about the likely need
for further intervention or debridement if
necessary.
Tissue samples for culture and histopathology
should be sent. At least two specimens from different sites should be sent for culture and sensitivity [27]. If the infected implant is removed, it
can be directly sent to a microbiological lab to
obtain samples for culture and sensitivity. There
have been multiple innovations to improve the
culture yield from removed implants. Techniques
like sonication use high-frequency sound waves
to dislodge bacteria from the biolm present on
the retrieved implants [28]. Multiple studies have
shown that this technique signicantly improves
the culture yield. The debridement procedure
may be combined with sequesterectomy. Highow irrigation is used for the removal of microscopic infected tissue [29]. The choice of
irrigation uid is subjective, and various studies
comparing normal saline, distilled water, and
iodine solutions show similar outcomes [29].
There is no denitive advantage of high-pressure
lavage over low-pressure lavage, as shown by
FLOW trials.
If the fracture gets destabilized by the procedure, some form of external xation may be
required [30, 31]. The use of antibiotic spacers
may be considered if there is considerable dead
space after performing debridement. This method
of slow, sustained delivery of high concentrations
of antibiotics is effective in controlling local
infections [32]. Antibiotic spacers can also be
subsequently converted to a membrane-induced
osteogenesis technique.
In the case of infected intramedullary nails,
the use of a reamer irrigator aspirator system
after implant removal has been shown to produce
signicantly better outcomes [33]. The removed
implant can be replaced with either an antibioticloaded nail, a new nail, or an external xation
device, depending on the severity of the
infection.
14.3.3 Soft Tissue Coverage
The nutrition of bones lies in soft tissue.
Antibiotics given by the systemic route need
14 Algorithm onTreatment inFracture-Related Infections
191
good vascularity to reach bones. Soft tissues primarily get damaged after trauma or infection,
and once debrided for infection, the bone
becomes denuded and lacks vascularity. When
analyzing a fracture-related infection and planning its treatment, we need to provide adequate
soft tissue coverage to improve the chances of
healing of infection and facilitate fracture union.
There are multiple options, like ap surgery and
negative pressure wound therapy, which help
improve the soft tissue cover of the infected
wound. When planning a revision of fracturerelated infection, a plastic surgeon should be
included in the team to plan an appropriate local,
pedicled, or free ap surgery. Negative pressure
wound therapy has shown promising results in
gradually draining the wound and enhancing
granulation tissue formation, and improving soft
tissue coverage. However, its use as a denitive
treatment for coverage of soft tissue defects is
not clear [34]. Both methods have their benets
and drawbacks. Flap surgery provides primary
closure and rapid return of vascularity of tissues.
Negative pressure wound therapy system is a
simple method that can be applied at all anatomical sites and can be used even if the ap surgery
fails [35]. It has a low cost compared to a free
ap and is easily available. Flap coverage surgery requires a specialist consultation with a
high skill level to successfully perform a ap
surgery, something which might not be available
in a low-resource setting hospital. Negative pressure wound therapy requires regular dressing
changes, and the patient needs to remain bedridden for a prolonged time, thereby increasing
anxiety levels and depression [36]. Whatever the
method, a vital soft tissue cover, after a thorough
and judicious debridement of infection, remains
the cornerstone of managing fracture-related
infections.
14.3.4 External Fixation
External xation is a powerful tool in the treatment of orthopedic infections. It provides a socalled implant holiday to the local soft tissues to
allow them to heal. Pathogens form a biolm on
internal xation devices and resist the action of
antibiotics. This biolm inhibits the biology of
fracture union and can gradually turn the bone
into a sequestrum. The only reliable way to treat
the biolm is to remove the associated internal
xation device with it. The internal implant has
to be replaced with an external xation device.
External xation devices have minimal contact
with infected tissues and hence are unlikely to
provide a surface for the formation of biolm [4,
37]. Despite being cumbersome and heavy, exter-
nal xation devices can serve as a temporary or
denitive method of treatment.
Various types of external xation devices are
available. It may be a monolateral xator or an
Illizarov ring xator. Ring xators are considered
to be more stable and can be used for denitive
xation [37]. They can also be used for alternate
strategies like bone transport as and when
required. There is multiple high-level evidence to
support the use of external xation as a gold standard in reconstructing residual bone defects after
treating bone infections.
The use of external xation devices for fracture stabilization has multiple drawbacks. Apart
from being bulky and cumbersome, they restrict
the joint range of movement and prolong the time
for limb rehabilitation. They require regular
dressings and sometimes the patient may have to
be bedridden for a prolonged period of time.
However, given the mandatory requirement of
maintaining bone alignment and stability, external xation plays a unique role in managing
fracture- related infections.
Case 2 Example of Ring xator being used as
denitive treatment of middle third tibia posttraumatic osteomyelitis.
A 55-year-old male patient with sustained
compound grade 3b tibia fracture. He was managed initially with ex xator and soft tissue coverage, and presented to us with middle third tibia
osteomyelitis and draining sinus through the ap
(Fig.14.7).
Figure 14.8 is X-Ray after doing debrifdement, sequestrectomy, xing with illizarov ring
xator, and doing corticotomy.
192
R. Parwani
Fig. 14.7 A 55-year old male patient with sustained
compound grade 3b tibia fracture. He was managed initially with ex xator and soft tissue coverage. Hepresented
to us with middle third tibia osteomyelitis and draining
sinus through the ap
Figure 14.9 is X-Ray at end of bone transport
with both segments meeting at center.
Figure 14.10 is X-Ray after consolidation of
regenerate, taken before frame removal.
Figure 14.11 is X-Ray of complete union.
14.3.5 Antibiotic Loaded Cement/ Bioceramics
Orthopedic infections involve bone and implants
and are known to respond slowly to antibiotics.
The effective management of orthopedic infections requires the sustained presence of antibiotics
in the soft tissue, in a high enough concentration
near the bone–implant interface [32]. This high
level of serum concentration is difcult to sustain
by administering antibiotics through the oral or
intravenous routes and may lead to systemic complications. Such high concentrations are best
Fig. 14.8 X-Ray after doing debrifdement, sequestrectomy, xing with illizarov ring xator, and doing
corticotomy
achieved with some form of local antibiotic delivery system. Antibiotic cement, polymethyl methacrylate (PMMA), was the rst such biocompatible
material discovered that could serve as a vehicle to
provide sustained elution of antibiotics to maintain
a soft tissue concentration of antibiotics well above
the minimum inhibitory concentration (MIC) of
bacteria. Thus, PMMA was the rst local antibiotic delivery system to be developed commercially. Vancomycin and gentamicin are the most
popular antibiotics that are combined with PMMA.
It is available in an antibiotic mixed pre- constituted
form or antibiotics can be mixed during surgery as
well. The antibiotic-loaded PMMA is known to
provide the highest in situ diffusion of antibiotics
and is considered to be the gold standard.
Antibiotic-loaded cement coated onto intramedullary implants can provide fracture stability in the
absence of formal implants [39, 40]. This can act
as a temporary measure, while high concentrations
of antibiotics eluted into soft tissue allow the tis-
14 Algorithm onTreatment inFracture-Related Infections
Fig. 14.9 X-Ray at end of bone transport with both segments meeting at center
193
sues to regenerate. They have been proven very
effective in (1) early suppression of infection, (2)
showing a several-fold reduction in the recurrent
infection incidence, (3) minimizing the risk of
pathological fracture due to internal reinforcement, (4) providing early recovery of extremity’s
function, and (5) creation of favorable conditions
for bone structures restoration [40].
However, there have been some concerns
about the heat of polymerization of PMMA,
which may inactivate the active antibiotic [41]. It
also requires a second surgery for cement
removal, since it is a nonbiodegradable product.
Vancomycin and gentamicin are the most popular
antibiotics that are combined with
PMMA. Insertion of properly shaped PMMA
models can help provide accurate stability to the
infection site by acting as temporizing spacers.
Various other materials, which can act as
vehicles for local antibiotic delivery, called bio
ceramics, have been discovered. Some examples like calcium sulfate, calcium phosphate,
and hydroxyapatite are effective. They were
found to have similar properties without the
drawbacks of PMMA.The newer systems combine osteoinductive and osteoconductive properties, which enhance bone union by facilitating
osteoblast proliferation and osteoclast differentiation. Bioceramics are combined with antibiotics and constituted as scaffolds to provide a
controlled, sustained release of antibiotics to
the local soft tissue [42]. The biocomposite
material is arranged in a porous matrix and,
being biocompatible, provides a structure for
the neighboring cells to inltrate and differentiate into osteoblasts and provide osteoinductive
properties. As the scaffold dissolves, the material gets absorbed without any local reaction
thus obviating the need for a second surgery to
remove the product. The various commercially
available products and their regulatory approval
are listed below.
194
R. Parwani
Fig. 14.10 X-Ray after consolidation of regenerate, taken before frame removal
14 Algorithm onTreatment inFracture-Related Infections
Fig. 14.11 X-Ray of complete union
195
S.n. Carrier
agent From
1. PMMA Gentamicin Beads impregnated with
the antibiotic
Tobramycin Bone cement
incorporating the
antibiotic
Antimicrobial
Gentamicin and
Clindamycin
Bone cement
incorporating the
antibiotic
Gentamicin and
vancomycin
Bone cement
incorporating the
antibiotic
Gentamicin Beads impregnated with
the antibiotic
2. Hydroxyapatite _ Xenograft granules that
can be preloaded with
suitable antibiotic
3. Hydroxyapatite/
calcium sulfate
Gentamicin Synthetic bone substitute
incorporated with the
antibiotic
Commercial
products Ofcial approval
®
®
FDA, 2003
FDA, 2007
FDA, 2019
Palacios G
Simplex P
®
Copal
G+C
®
Copal
FDA, 2019
G+V
®
Septopal
The Therapeutic Goods
Administration,
Australia, 2020
Endobon
Cerament
®
FDA, 2011
®
G Health Canada, 2018
196
R. Parwani
S.n. Carrier
4. Calcium sulfate Tobramycin Bone graft substitute
5. Calcium phosphate _ Synthetic bone substitute
6. Calcium
phosphate/collagen
7. Collagen Gentamicin Matrix impregnated with
14.3.6 Membrane-Induced Osteogenesis (Masquelet Technique)
Antimicrobial
agent From
incorporating the
antibiotic
_ Synthetic bone substitute
that can be preloaded
with suitable antibiotic
that can be preloaded
with suitable antibiotic
_ Synthetic bone cement
that can be preloaded
with suitable antibiotic
Synthetic bone substitute
that can be preloaded
with suitable antibiotic
the antibiotic
and the cement spacer is removed. The residual
space is lled up with autologous or heterologous
bone grafts, and appropriate internal xation is
used to provide stability. After the second step,
Management of posttraumatic or infected bone
defects is a challenging job because of the presence of latent infection, poor soft tissue healing,
and regenerative capabilities. If these defects are
present in the bones of the lower limb, they can
cause signicant shortening which will result in
some form of permanent disability to the patient.
One of the techniques that is a good alternative to
bone transport is the membrane-induced osteogenesis technique. The method was popularized
by Alain Masquelet in the late 1970s for aseptic
nonunion in bones of lower limbs, especially
tibia [43]. Over time, the technique has been
adapted for treating long bone defects in all long
bones and a variety of etiologies.
The technique is essentially a two-step procedure and does not need specialized implants. The
rst step consists of a good debridement, sequestrectomy, soft tissue coverage, and placement of
antibiotic-loaded cement to act as a spacer and
internal splint. After a variable period of time of
one to one and a half months, when the defect site
is surgically opened, a distinct soft tissue membrane is found surrounding the cement spacer
[43]. This membrane is incised longitudinally,
the fracture consolidates and unites well.
Various animal studies have shown the presence of increased vascularity and mesenchymal
stem cells that secrete growth factors in the
induced membranes [43]. This method is useful
in the osteogenesis of all long bones, including
the femur, humerus, and tibia. Animal model
studies have shown good vascularity and thicker
membranes when the technique is used in bones
having better muscular envelope.
Membrane-induced osteogenesis best works
in situations of short-segment defects and/or noncircumferential defects [44]. The defects of more
than 10 cm require excessive autologous bone
grafts and should be considered for bone transport or vascularized bone grafts. Draining
wounds, poor soft tissue coverage, and smoking
are relative contraindications [44].
It is critical to know when to use the
membrane- induced osteogenesis technique. We
believe the bone defects should be at least 50% of
the diameter of the long bone, and a gap of at
least 1–2cm should be present. Santolina etal.
identied 10 risk factors of nonunion. The presence of four or more risk factors should be an
Commercial
products Ofcial approval
®
Osteoset
Stimulan
Cerasorb
Biopex-R
Cerasorb
Ortho Foam
Callatamp
FDA, 2004
®
FDA, 2015
®
M FDA, 2012
®
The Pharmaceutical and
Medical Devices Agency,
Japan, 2000
®
FDA, 2020
®
Health Canada, 2008
14 Algorithm onTreatment inFracture-Related Infections
197
indication for considering the Masquelet technique [45]. Some researchers are working on a
method of combining two methods—membraneinduced osteogenesis and bone transport—to
achieve better union rates and improve the quality of regeneration. Thakeb etal. have shown a
better outcome for managing larger bone defects
with a combination of induced membrane and
bone transport, with better union rates [46].
14.4 Algorithm ofApproach
toInfection
The primary aims of the treatment of fracturerelated infection are
1. Fracture consolidation.
2. Eradication of infection as the outcome (in
certain cases, initial suppression of infection
until fracture consolidation is achieved).
3. Healing of the soft tissue envelope.
4. Restoration of function.
5. Prevention of chronic infection/osteomyelitis. [37]
There have been multiple attempts by various study groups across the world to develop
algorithms to treat orthopedic infections. But a
consensus remains elusive. This is because of a
lack of standardization of diagnostic criteria,
classication, and treatment regimens. Some
good publications include the review article
published by Sylvian etal. [47] We have developed our algorithm, which looks to manage
fractures, implants, soft tissue defects, bone
gaps, and comorbid factors. We emphasize the
role of shared decision- making in a team comprising the orthopedic surgeon, plastic surgeon,
and infectious disease specialist (Figs. 14.12
and 14.13).
Fig. 14.12 Flow chart depicting the diagnosis and management of suspected FRI (Fracture-Related Infection)
198
Fig. 14.13 Flow chart depicting a decision-making process for treatment of infected nonunion
R. Parwani
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