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386
K. M. Emara et al.
2. Radiological signs: any one of
• bone lysis (at the fracture site, around the
implant)
• implant loosening
• sequestration (occurring over time)
• failure of progression of bone healing (i.e.
non-union)
• presence of periosteal bone formation (e.g.
at localizations other than the fracture site
or in case of a consolidated fracture)
3. A pathogenic organism identied by culture
from a single deep tissue/implant (including
sonication uid) specimen taken during an
operative intervention.
4. Elevated serum inammatory markers:
• erythrocyte sedimentation rate (ESR)
• white blood cell count (WBC)
• C-reactive protein (CRP)
26.8 Treatment
The general treatment principles for FRI include:
1. radical debridement
2. implant handling
3. systemic and local antibiotics
4. defects reconstruction of bone and soft
tissues
5. functional recovery
Multidisciplinary teams, including surgeons,
infectious diseases specialists, pharmacists, and
microbiologists, are recommended to improve
the treatment efcacy [17]. Selection of the specic treatment methods should consider many
factors, such as infection site and duration, pathogen type and virulence, host immunity and
requirements, and expectations of the patients.
26.8.1 Radical Debridement
Radical debridement is one of the most efcient
methods for reducing the bacterial burden of
affected tissues, which is the key to reducing the
risk of infection recurrence. Excision of bone or
tissue, excision of poorly perfused tissue, and
removal of all non-essential foreign bodies (e.g.,
broken screws, sutures) are typical components
of debridement [18]. Although ‘oncologic resection’ of infected bone has been proposed, a more
prudent strategy with bone excision until uniform
punctate bleeding is detected is indicated [19].
This is predicated on the concept that viable
infected bone can recover with antibiotic treatment (i.e. systemic and local).
The purpose of irrigation is to reduce bacterial
load and remove loose debris. To prevent bacterial seeding in soft tissue and bone, it should be
conducted using normal saline at low pressure
[20]. Currently, the use of chemicals is not recommended since they may increase cell toxicity
[21]. In order to fully clean the surgical eld and
reduce the bacterial burden after debridement, a
signicant amount (depending on the anatomic
location) of irrigation uid should be employed.
26.8.2 Implant Handling
The existence of a fracture is one of the key
characteristics that distinguish FRI from
PJI. Fracture stability is crucial not only for
fracture union but also for infection prevention
and treatment [22]. As fracture xation devices
primarily target fracture consolidation, they can
be removed after the fracture has healed (in contrast to PJI), eliminating the biolm with a high
likelihood of eradicating the infection and preventing chronic infection. This indicates that
total eradication of an infection may not always
be the primary objective. In select circumstances, antibiotic suppression therapy has been
established as an alternative [1].
Based on this, two main surgical concepts
should be considered. The rst concept consists
of debridement, antimicrobial therapy, and
implant retention (DAIR). The second consists of
debridement, antimicrobial therapy, and implant
removal if the fracture is healed or implant
exchange (in one or multiple stages) if the fracture is not healed.
In every case, special attention should be paid
to the stability of the fracture in order to obtain
union and treat the infection [23].
26 Infective Complications After Trauma Surgeries
387
Several criteria determine whether the implant
should be removed or not. Implants should be
removed or exchanged when the implant and
fracture are unstable, reduction is not acceptable,
or the host physiology is substantially impaired.
In uncommon circumstances when healing cannot occur due to a compromised host or a severe
infection, amputation, or a nonsurgical method
with or without (lifelong) antibiotic suppression
may be the only therapy option (e.g., in elderly
patients with compromised host physiology) [1].
26.8.3 Systemic andLocal Antibiotics
As soon as culture results and corresponding
antibiotic susceptibility patterns from the intraoperatively obtained samples are available,
empiric antibiotics are changed to targeted therapy. Initial empiric therapy should be broadspectrum and include a lipo/ glycopeptide and a
gram-negative bacillus-targeting drug.
The current recommendation is that IV therapy be switched to oral antibiotics after
1–2weeks, when the soft tissues are stable, and
the wounds are dry [9]. In case of implant retention or exchange, a total treatment duration of
12weeks is recommended. If the internal device
is removed, antibiotics are given for in total of
6weeks [9].
Biolm-active antibiotics include rifampicin
for staphylococcal infections and uoroquinolones for Gram-negative bacteria, assuming susceptibility testing. They should be administered
only after thorough debridement to reduce bacterial burden and when wounds are dry to prevent
superinfection with resistant germs [24]. Because
of the rapid emergence of resistant microorganisms, rifampicin must be given with a companion
antibiotic [25].
The presence of an infection that is difcult to
treat determines whether the antibiotic regimen is
curative or suppressive. In the latter scenario,
antimicrobial therapy controls the infection until
the fracture heals and the implant may be
removed.
All FRI patients should have a baseline blood
analysis available, especially patients who will
receive IV antimicrobial therapy, including baseline inammatory markers, full blood count,
electrolytes, and liver- and renal function tests.
They should be repeated at least twice weekly, as
common side effects of high-dose IV antibiotics
include bone marrow suppression, hepatitis, and
nephrotoxicity.
26.9 Local Antimicrobial Therapy
The benet of achieving a very high local concentration of antimicrobials with limited systemic exposure is persuasive, especially in light
of decreased blood ow to the site of infection
and necrotic bone tissue [1, 26]. Furthermore,
after an extensive debridement they can be an
important treatment option for dead space
management.
The drug release has its peak within the rst
7 days and rapidly decreases thereafter [26].
Standard antibacterial agents in spacers and
beads are aminoglycosides (e.g., gentamicin,
tobramycin), either alone or in combination with
vancomycin. Antibiotics have traditionally been
incorporated into PMMA cement [27]. PMMA
carriers must be removed in a second procedure
three to four weeks after insertion. A bioabsorbable substance as a vehicle for local antibiotic
delivery, on the other hand, does not necessitate a
second surgical procedure and may permit bone
regrowth [28]. Studies on bioabsorbable bone
substitutes (BBS) impregnated with antibiotics
for the management of FRI reported reinfection
rates ranging from 0% to 14.3% [28]. Calcium
sulfate with hydroxyapatite, when used as an
antibiotic carrier, has been proposed to enhance
bone growth [29].
26.9.1 Defects Reconstruction
ofBone andSoft Tissue
Autogenous bone graft remains the gold standard
for the treatment of bone defects shorter than
2.5cm [30]. As for large segmental bone defects,
the selection of reconstruction procedures
depends on numerous aspects, such as the sur-
388
K. M. Emara et al.
geons’ experience, the location and extent of the
bone defect, comorbidities, and compliance of
the patient. The Ilizarov technique, the Masquelet
approach, and the free vascularized bular
grafting technique are the most common procedures for reconstructing segmental bone defects.
26.9.1.1 Ilizarov Technique
If the defect is small (<2cm), the limb can be shortened to give good bone contact and allow skin closure. If the defect is up to 4cm in the tibia and 6cm
in the femur, the limb can be acutely shortened to
give bone contact, but this will produce a signicant
limb length discrepancy that must be addressed.
Within the Ilizarov xator, it is possible to relengthen the bone through a separate corticotomy,
away from the site of infection. In larger defects,
gradual defect lling by Ilizarov bone transport has
been shown to be a safe and effective method of
securing union and eradicating infection.
Several recent studies have demonstrated the
advantages of double-level bone transport over
single-level bone transport, including shorter
time with external xation, faster bone healing
time, fewer problems, and greater function recovery [31].
26.9.1.2 The Masquelet Technique
Also known as the induced membrane technique,
is another effective way to repair large bone
defects. A membrane is produced around the
cement block. After some weeks, the cement can
be removed, and bone graft packed into the defect
inside the carefully preserved membrane. If the
bone remains stable, this graft may consolidate
and remodel over many months [32].
26.9.1.3 Free Vascularized Fibular
Grafting
Vascularized bula graft is a successful method
for reconstructing a bone defect; however, a welltrained multidisciplinary team is essential to
eliminate the high risk of potential consequences,
such as stress fractures [33].
26.9.1.4 3D Printing
Recently, with the advent of three-dimensional
(3D) printing technology, individualized and
accurate reconstruction and repair are no longer
inaccessible. Liu etal. [34] reported employing
3D-printed porous Ti6Al4V scaffolds to repair
severe diaphyseal defects of the lower limbs and
achieving satisfactory postoperative functionality
and minimal complication rates in prospective
research.
26.10 Repair ofSoft Tissue Defects
In the absence of an adequate soft-tissue envelope ideal denitive soft-tissue coverage within
an orthoplastic technique should be conducted as
soon as possible.
Free faps, skin grafts, and rotational faps were
the most often selected methods for reconstructing soft tissues. Multiple criteria, including the
microsurgical experience of the surgeons, the
patient’s age, smoking status, the presence of
comorbidities, and the location and size of the
soft tissue defect, must be taken into account
when determining the precise techniques to
repair soft tissue defects.
Negative pressure wound therapy (NPWT)
can provide signicant convenience in the
treatment of both open fractures and
FRI.Regarding the use of NPWT in FRI therapy, there was insufcient evidence to support
its usage as a denitive FRI treatment [35].
Negative pressure wound therapy (NPWT)
should be utilized just as a bridge to denitive
soft tissue covering. It cannot serve as a substitute for denitive soft tissue reconstruction in
FRI and should not be utilized for longer than
approximately one week. Extended NPWT
may result in the colonization of resistant
organisms and an increase in infection rates
[36].
26.11 Rehabilitation
andFollow-Up
Early customized functional rehabilitation is
essential for all orthopedic trauma patients,
especially when infection develops. As FRI frequently involves a lengthy course of treatment,
26 Infective Complications After Trauma Surgeries
389
psychological support should also be made
accessible.
It is recommended to follow up the patient in
regular intervals for a minimum of 12 months
after cessation of therapy in a specialized
inter- disciplinary outpatient clinic [37].
Follow-up outpatient visits generally consist of a
wound inspection, radiological evaluation of the
fracture, and monitoring for complications or
recurrence of infection.
26.12 Prevention ofFRI
Several preventive measures are currently considered as very effective with a high level of evidence (grade IA) according to guidelines [38].
These include:
26.12.1 Pre-operative Measures
26.12.1.1 Skin Preparation Solutions
Chlorhexidine, iodine, and alcohol are the most
common solutions used for skin preparation in
orthopedic surgery. Due to its limited duration of
action, alcohol is typically utilized in conjunction
with other antiseptics. There is no consensus on
the recommended solution.
26.12.1.2 Skin Hair Management
There may be little difference in SSI risk between
using clippers or hair removal lotion versus not
removing hair (evidence of low certainty) [39].
However, there are likely fewer SSIs when hair is
not removed when compared to razor shaving
(moderate-certainty evidence). There may be a
little reduction in SSIs when hair is removed on
the day of surgery as opposed to the day prior.
26.12.2 Peri-operative Management
26.12.2.1 Drapes
Adhesive drapes, especially those with antimicrobial characteristics, have been demonstrated
to reduce the incidence of wound contamination.
However, if drape adherence is impaired and
wound edge peeling occurs, this advantage may
be lost and the danger of wound infection may
increase [40].
26.12.2.2 Double Gloving
Double gloving reduces perforations, yet there
is no data of high quality addressing the relationship between gloving techniques and FRI
rates [41].
26.12.2.3 Antibiotics Coated Implants
According to numerous preclinical research,
antibacterial coatings have been proposed to
reduce bacterial adherence and biolm development [42].
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Infective Complications After Open Fractures
KhaledM.Emara, RamyA.Diab,
andMohamedO.Eissa
27
27.1 Introduction
Open fractures are serious injuries with a reported
incidence of 30.7 per 100,000 persons each year
[1]. Infection remains one of the most signicant
complications in the treatment of open fractures,
despite the fact that outcomes have improved
over the past century. The underlying bone is susceptible to direct contact with contaminating
agents if the tissue barrier between the fracture
zone and the environment is compromised.
An open fracture is an injury where the fractured bone and/or fracture hematoma are exposed
to the external environment via a traumatic violation of the soft tissue and skin. The skin wound
may lie at a site distant from the fracture and not
directly over it. Therefore, any fracture that has a
concomitant wound should be considered open
until proven otherwise [2].
Classication of open fractures is of the
utmost importance, as the severity and extent of
soft tissue damage determine a complex treatment concept involving surgical and non-surgical
measures. In 1976, Gustilo and colleagues established their classication system [3], which
allowed them to draw therapeutic conclusions for
an individual fracture which was then modied in
1984 [4].
Other classication systems like the classication system of Tscherne and Oestern [5] and
the AO Müller Classication [6] provide more
rened descriptions of the local situation, as
lesions of bone, soft tissues, and neurovascular
structures are evaluated separately, along with the
level of contamination. On the other hand, their
detailed classication of various parameters in an
open fracture results in a descriptive complexity
that makes daily communication more challenging than Gustillo’s classication. After the initial
debridement, the classication of an open fracture must be reassessed [5].
27.2 Epidemiology
The risk of fracture-related infection (FRI) in
high-impact open fractures is up to 30% [7]. WeizMarschall [8] reported in a survey of the literature
the risk of acute infection in open fractures and it
was 0% infection rate in Gustilo type I, up to 12%
in type II, and up to 50% in type III fractures.
27.3 Pathophysiology
27.3.1 Contamination andVirulence
Rates of primary colonization have been reported
K. M. Emara · R. A. Diab · M. O. Eissa (*)
Department of Orthopedic Surgery, Ain Shams
University, Cairo, Egypt
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
P. Ruggieri et al. (eds.), Bone and Joint Infections, https://doi.org/10.1007/978-3-031-96383-4_27
to be between 70 and 80 percent, depending on
the nature of the accident. Smears reveal Gram-
393
394
K. M. Emara et al.
positive Staph. aureus and epidermidis and
Gram-negative Bacilli, Pseudomonas,
Acinetobacter, or Enterobacteria the majority of
the time [7, 9, 10].
Most infections in open fractures are of nosocomial origin as the causative micro-organisms
of infection differ from those found in initial
smears [11].
Following an open fracture, polymicrobial
infections are associated with increased antibiotic requirements and an increase in amputations.
A higher fracture grade (III), working in agriculture, the need for a blood transfusion, or the need
for additional surgical debridement are all associated with the development of a polymicrobial
infection following an open fracture [12].
27.5.1 Laboratory Examination
Due to multiple inuencing factors and differences in half-life times of serum inammatory
makers, their diagnostic values on FRI differ.
• WBC usually rises to the highest level from
• ESR usually increases to the highest level from
• CRP usually goes up to the highest level on the
27.4 Risk Factors
A variety of factors determine the clinical results
following an open fracture. Polytraumatized
patients are at high risk because severe trauma is
commonly accompanied by complex musculoskeletal injuries and a compromised host
immune response [13]. Risk factors can be
divided into:
External factors (environmental factors) [14]:
1. Injury type and degree.
2. Injury site.
3. Pathogen virulence.
4. Prophylaxis and treatment methods.
Internal factors (host factors)
1. Immune status.
2. Lifestyle.
3. Comorbidity of the patients.
• Aside from surgery, bacterial type and viru-
(a) Serum D-dimer may be a useful indicator for
(b) Interleukin-6 (IL-6) had a similar diagnostic
(c) Platelet count to mean platelet volume ratio
(d) Wound alpha defensin [24].
(e) Cluster of differentiation (CD) 64 [25].
day 1 to day 3 after surgery and is back to normal within 4 to 6days [15].
day 7 to day 11 after surgery and decreases to
normal after 6weeks gradually [16].
second day following surgery and returns to
normal after 2weeks [17]. If serum CRP level
continuously increases from fourth to seventh
day after surgery, a high probability of FRI
should be considered after the exclusion of
infection in other systems or persistent systemic
inammatory stress status of the patient [18].
lence can also affect the levels of the inammatory markers, meaning that high-virulence
and drug-resistant bacteria are often associated with higher levels [19].
New markers:
the evaluation of infected nonunion, with
sensitivity and specicity at 75% and 91.2%
[20, 21].
value for FRI, in comparison to ESR and
CRP [22].
[23].
27.5 Clinical Presentation
andInvestigations
The clinical presentation depends on; duration of
infection, type of microorganism, anatomic localization, mechanism of the trauma leading to fracture, and type of surgery that has been performed.
27.5.2 Imaging Procedures
The indications to request diagnostic imaging:
1. Assessment of fracture healing, fracture
reduction, and stability of the osteosynthesis
construct.
27 Infective Complications After Open Fractures
395
2. Acquire more certainty regarding the presence or absence of FRI.
3. Visualization of the anatomic details of the
infection such as its extension, the presence
of sequestra, sinus tracts, and subcortical
abscess [26].
27.6 Nuclear Imaging
Applying radioisotopes to detect and track
physiological and pathophysiological changes,
such as fracture healing, bone remodeling, and
the inammatory response to an infection.
Recently, the use of hybrid camera systems that
combine nuclear imaging with CT (single photon emission computed tomography (SPECT))
(SPECT/CT, PET/CT, or PET/MRI) has resulted
in improved accuracy and more anatomical
details [27]. The consensus denition classies
nuclear imaging as suggestive despite its excellent diagnostic accuracy in establishing the
diagnosis of FRI [26].
27.7 Microbiology
Surgical exploration and microbiological sampling are the pillars of diagnosis and, more critically, the key determinants for antimicrobial
treatment. Intraoperative sample collection is
crucial to the diagnostic process since it permits
the interpretation of histological and microbiological tests. It is essential to identify the causative pathogen(s) for antimicrobial therapy to be
effective [28].
Recommendations during sample collection:
1. Collect preferably ve, representative deep
tissue samples from the site of perceived
infection and adjacent to implants [9, 26].
2. Unused surgical instruments should be used
for each sample obtained to avoid crosscontamination [29].
3. The samples should be numbered and labelled
with the anatomical localization and sent for
microbiological and histopathological
investigation.
4. Supercial swabs and surface biopsies from
open wounds should be avoided as there is a
high chance of culturing bacteria belonging
to the skin microbiome colonizing the
wound [9].
5. Whenever possible (except in septic patients),
systemic antibiotics should be avoided
2 weeks prior to sampling to avoid falsenegative culture results [9].
6. Different culture media should be considered to
cover both aerobic and anaerobic pathogens.
It is advised that the culture time is generally
for 7day.s but can be extended to 14days in
suspicion of slow-growing strains, such as
Cutibacterium acnes [9, 26].
If a highly virulent pathogen (such as
Staphylococcus aureus) is found in a single sample of deep tissue, a strong suspicion of infection
should be raised [30].
Several institutes include the sonication of
extracted implants in their diagnostic procedures.
Sonication is a valuable supplement to conventional tissue culture in implant-associated infections, particularly in patients who have been
pre-treated with antibiotics. However, its diagnostic value in FRIs still needs to be established,
and tissue cultures remain the gold standard [26,
31, 32].
27.8 Molecular Technologies
1. Polymerase Chain Reaction.
Scientic data on molecular techniques, such
as PCR, in the eld of FRI are scarce [31]. These
tests are fast diagnostic procedures that can distinguish between viable and nonviable bacteria.
However, the high sensitivity of PCR carries the
risk of producing false positive results due to
contamination [33].
2. Next-generation sequencing (NGS).
Capable of sequencing all DNA contained in a
given sample, providing a full image of the
microbial genomes present; proven effective in
396
K. M. Emara et al.
culture-negative settings for the detection of
pathogens [34, 35].
27.9 Histopathology
The presence of visible microorganisms in deep
tissue, as conrmed by histological investigation
using particular staining procedures for bacteria
(e.g., Gram stain, Ziehl-Neelsen stain for tuberculosis, or Grocott methenamine silver stain for
fungi), is considered conrmation of FRI. [30] In
late FRIs, an infection can be reliably conrmed
if the histological investigation reveals the presence of more than ve polymorphonuclear neutrophils (PMNs) per high-power eld. Aseptic
nonunion can be identied by the absence of neutrophils in any high-power eld [36].
27.10 Management ofOpen
Fractures
The goals of treating an open fracture are wellknown and include preventing infection, achieving bony union, and restoring function. In order
to accomplish the other goals, the prevention of
infection is the most important measure. Posttraumatic bone infection (fracture-related infection) is a devastating complication that frequently
impedes the patient’s rehabilitation and treatment. This infection increases treatment costs
and duration, causes physical and social losses,
and diminishes patients’ quality of life and functional independence.
27.10.1 Principles ofSurgical Care
forOpen Fractures
27.10.1.1 Initial Assessment
andStabilization
A trauma patient must be evaluated according to
Advanced Trauma Life Support (ATLS) and
institutional protocols. Then, open fracture
wounds can be dressed with sterile, moist gauze,
and clinical realignment of the limb can be
achieved using a temporary splint or traction.
Irrigation
Washing the wound with large volumes of uid
will eliminate macro-level contamination and
clots that may obscure the view of deeper levels
of contamination or damaged tissue. Once the
macro contamination has been eradicated, irrigation serves to reduce the bacterial contamination
of the remaining healthy tissue.
27.10.1.2 Appropriate Intravenous Antibiotics
Type ofAntibiotic
Administration of antibiotics is best considered
therapeutic, rather than prophylactic, because of
the high risk of infection in the absence of antibiotics [37].
Although debate still surrounds some aspects
of antibiotic administration for open fractures,
[38] the following generalizations can be made:
• Type I injuries should receive cefazolin 1–2
grams/8 hours or equivalent gram-positive
coverage.
• Type II or type III injuries likely benet from
the addition of adequate gram-negative cover-
age, typically with an aminoglycoside (genta-
mycin 80 mg/8–12 hours) or a
fourth-generation cephalosporin. Ampicillin-
sulbactam may be an acceptable alternative
for type IIIa fractures [39].
• Injuries at risk for anaerobic infections (eg,
farm injuries, severe tissue necrosis) probably
benet from the addition of penicillin (ve
million-ten million units/24 hours) or
clindamycin and consider metronidazole.
• Tetanus immunization and Prophylaxis.
A tetanus toxoid booster should be administered to any patient with an open fracture who
has not completed the tetanus toxoid immunization or has not received a booster within the past
5 years. If the wound is susceptible to
Clostridium tetani contamination, tetanus toxoid should be combined with 250.500 IU of
human tetanus immune globulin (HTIG). In
addition, if it has been more than 10years since
the patient’s last tetanus booster or if the