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Osteomielitis Cronica

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Understanding and 25

Treating Chronic
Osteomyelitis
David W. Lowenberg | Markus Rupp | Volker Alt

Sir Alexander Ogston (1844–1929), a professor of surgery

HISTORY in Aberdeen, described osteomyelitis as a “boil of the bone
marrow” and identified microorganisms in acute abscesses.
Osteomyelitis can occur for a variety of reasons and is often He was the first to name these bacteria staphylococci at the
a result of open fractures. Therefore it is quite obvious that suggestion of Geddes, a Greek professor in Aberdeen, because
osteomyelitis has accompanied humankind and also animals the bacteria were growing in masses like bunches of grapes.10
over thousands or even millions of years. The most likely Key work on the management of osteomyelitis in the early
oldest evidence of osteomyelitis was found in a 250- to 20th century was done by the American surgeon Hiram
290-million-year-old infected spinal fracture of a dimetrodon Winnett Orr (1877–1956), with detailed descriptions of
Permian reptile. Also, an approximately 500,000-year-old surgical protocols, postoperative management, and out-
skeleton of a Java man (Homo erectus) shows possible signs of comes.4,11,12 In his protocol, all necrotic bone was to be
an infected nonunion.1 The Edwin Smith Papyrus (3000–2500 removed with “saucerisation” of the resulting cavity, followed
BC) is often cited as the earliest written evidence of bone by immobilization of the limb in a neutral position.13
diseases, including descriptions of bone infection.2,3 The discovery of penicillin by Sir Alexander Fleming
In ancient times, Hippocrates (460–370 BC) described (1881–1955) in 1928 revolutionized the whole field of
the link between open fractures and necrosis of the bone.4,5 medicine, including the treatment and outcome of osteo-
The Romans also contributed to a deeper understanding myelitis. One of the first reports on the new “wonder drug”
and treatment of osteomyelitis; Celsus, for example, recom- in osteomyelitis from the Royal Hospital of Sick Children in
mended débridement and the importance of preserving vital Glasgow in 1948 showed a tremendous decrease in mortality
bone tissue.6 He emphasized that débridement should when penicillin was used in the treatment of hematogenous
continue until bleeding bone is encountered. Today, this osteomyelitis. He also observed radiographical restoration
has been coined by the late George Cierny as the “paprika of more normal bone with the induction of this treatment.14
sign” and remains an important hallmark in the current Advancing internal fixation techniques were also accom-
surgical débridement procedure. panied by the complication of osteomyelitis, which was named
The history of posttraumatic osteomyelitis has always been “postoperative osteomyelitis.” The Austrian Lorenz Böhler
associated with combat injuries. The invention of firearms led (1855–1973), one of the founders of modern orthopaedic
to a tremendous increase in open wounds and fractures, which trauma surgery, said in 1930: “The most dangerous innovation
often had to undergo amputation procedures, as described in treatment of fresh fractures is the fundamental operative
by Baron Jean Larrey (1766–1842), a military surgeon in approach, especially when practiced by novices, without the
Napoleon’s army. He is said to have performed more than appropriate indication and with insufficient asepsis and
200 amputations on soldiers at the “Bataille de la Moskova” inadequate materials.” He relied on Robert Koch’s recom-
on August 26, 1812, during Napoleon’s invasion in Russia. mendation to use safer and more reliable sterilization
Key discoveries in bacteriology and antisepsis by Louis techniques with the use of heat and steam compared with
Pasteur (1822–1895), Robert Koch (1843–1910), and Joseph disinfection with acid.15
Lister (1827–1912) significantly improved the understanding After World War II, improved surgical principles and
of the pathophysiology of bacterial infections, including techniques combined with proper dead-space management
osteomyelitis.7 Ignaz Semmelweis (1818–1865) of Budapest, by the introduction of local and free muscle grafts helped
described as the “saviour of mothers,” discovered the link to improve blood supply and outcome in patients with
between hand disinfection and the incidence of puerperal chronic osteomyelitis.16 Another important evolution was
fever. He found that the simple act of a physician washing made in the field of local delivery of antibiotics by poly-
one’s hands dramatically reduced the incidence of such methyl-methacrylate (PMMA) to achieve high local concentra-
infections.8 His observations were later confirmed by Louis tions in the bone and reduce systemic concentrations and
Pasteur, who identified microbes in puerperal fever but also systemic complications, such as nephro- and ototoxicity by
in furuncles and osteomyelitis.8 Joseph Lister described his aminoglycosides. The key discovery for this was made by
aseptic technique for surgery using carbolic acid,9 which led Hans-Wilhelm Buchholz for periprosthetic joint infections
to the term “Lister’s dressing,” and also discussed its applica- (PJIs) and reported in 1970.17 Sir John Charnley doubted
tion to open fractures. this concept and replied in a letter to Buchholz: “My dear

707
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uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
708 Section ONE — General Principles

Buchholz, nothing leaks out of stone.” However, Wahlig and disease and elevated blood sugar levels compromising local
Dingeldein could clearly demonstrate the favorable release and systemic host infection response systems.29,30 A lifetime
kinetics from different antibiotics out of PMMA,18 which risk of foot ulcers of approximately 25%, with the risk of
paved the way for the invention of PMMA-gentamicin beads spreading to the underlying bone, is mainly responsible
by Klaus Klemm (1932–2000) by enhancing the release of for the high incidence of chronic osteomyelitis in diabetic
antibiotics through a higher surface area of the PMMA carrier patients.
in small beads and proved successful for the treatment of Further systemic risk factors for osteomyelitis in adults
osteomyelitis.19 include peripheral vascular disease, pressure ulcers, and
Clearly, osteomyelitis is not a new ailment. It has been in surgical interventions, as well as age due to the immuno-
existence since the start of mammalian history. Its treatment compromised nature of aging.31–33 Immunocompromised
has been poor at best until the recent era. Clearly, certain patients after organ transplantation, hemodialysis, and
hallmarks of treatment have evolved over the past 250 years chemotherapy and patients with polymorphonuclear leuko-
that have helped form a foundation for our current treatment. cytes have also been found to be at an elevated risk for
These are further addressed throughout this chapter. osteomyelitis.34–37 Furthermore, intravenous (IV) drug abuse
is a significant risk factor for osteomyelitis.38

EPIDEMIOLOGY EPIDEMIOLOGY OF POSTTRAUMATIC AND

20 POSTOPERATIVE OSTEOMYELITIS
According to Lew and Waldvogel, chronic, nonhematog-
enously spread infection occurs secondary to a contiguous Besides systemic risk fractures, open fractures with bacterial
focus infection after trauma, from inoculation after surgical contamination of the soft tissue and bone are at increased
intervention, from infection secondary to vascular insuffi- risk for the development of osteomyelitis. Ramón Gustilo
ciency, or due to skin breakdown with wound creation due was one of the pioneers to scientifically assess the association
to peripheral neuropathy. Hematogenous spread can occur between the severity of tissue trauma and development of
due to a host of reasons. osteomyelitis. In one of his review articles,39 deep infection
rates in the setting of open fractures were found to be
EPIDEMIOLOGY OF HEMATOGENOUS anywhere from 2% to 50%. Based on his observational studies,
he proposed, together with Anderson, a new classification
OSTEOMYELITIS
system for open fractures depending on the severity of the
The epidemiology of hematogenous osteomyelitis still differs soft tissue lesion.40,41 This Gustilo-Anderson classification has
between developed and third-world countries. Chronic been widely accepted and adopted and uses three general
hematogenous osteomyelitis is seen less frequently in indus- types of injuries with a subclassification of type III lesions
trialized countries.21 Previous studies from Norway between and allows for an estimation of posttraumatic osteomyelitis
1965 and 199422,23 and Lithuania24,25 reported an annual risk depending on the type of injury. Types I and II open
incidence of hematogenous osteomyelitis of approximately fractures are associated with around a 2% risk of infection
10 to 14 cases per 100,000 children compared with approxi- as compared with 10% to 50% in type III injuries.39–41 In
mately 43 cases for Maori children.26,27 A recent comprehensive addition, type IIIC fractures with neurovascular lesions to
work on the epidemiology of osteomyelitis in the United the leg have a significantly greater risk of infection compared
States in a population-based historical cohort study from with types IIIA and IIIB.42,43 Court-Brown confirmed these
1969 to 2009 carried out in Olmsted, Minnesota,28 showed findings also for tibia shaft fractures treated by intramedullary
an incidence of 8 to 10 cases of osteomyelitis per 100,000 nailing in a review article, with infection rates of 0% to 3.2%
person-years in children. in injuries with mild soft tissue lesions (closed, Gustilo-
The same publication revealed an overall age and sex- Anderson types I and II injuries) compared with 17.5% to
adjusted independent annual incidence of osteomyelitis of 23.1% in Gustilo-Anderson type IIIB injuries with severe soft
21.8 cases per 100,000 person-years, including hematogenous- tissue injuries.44 The burden of disease of infected tibia
related, diabetes mellitus–related, contiguous, and iatrogenic fractures for the United States was recently estimated by Alt
causes.28 Interestingly, the incidence of osteomyelitis increased (Table 25.1), with approximately 1620 infections and financial
over this 40-year period from 11.4 cases per 100,000 person- costs of approximately $83.3 million per year. We feel this
years in the period from 1969 to 1979 to 24.4 cases per is probably underestimated due to the fact that many patients
100,000 person-years in the period from 2000 to 2009. The with posttraumatic chronic osteomyelitis are forced to simply
incidence tripled among individuals older than 60 years, live with the disease because reasonable treatment options
which is mainly attributable to diabetes-related osteomyelitis, are often not offered.
with an increase from 2.3 cases per 100,000 person-years in Pressure ulcers, mainly in bedridden patients, with contigu-
the period from 1969 to 1979 to 7.6 cases per 100,000 person- ous spread to the bone are mainly responsible for osteomyelitis
years in the period from 2000 to 2009. of the pelvis and of the calcaneus.45–47 This is frequently the
case in people suffering from paraplegia and quadriplegia.
EPIDEMIOLOGY OF OSTEOMYELITIS SECONDARY In most cases, polymicrobial infections with different organ-
TO VASCULAR INSUFFICIENCY AND isms from the external environment can be found.
Chronic osteomyelitis is not only a consequence of certain
SYSTEMIC DISORDERS
predisposing factors but is also associated with an increased
Diabetic patients suffer from peripheral neuropathy with risk of the patient developing other morbid conditions and
loss of protective sensation combined with microvascular even an increased chance of death. Chronic inflammation

Descargado para Diego Alvarado Gómez (diego.alvarado.g@usach.cl) en University of Chile de ClinicalKey.es por Elsevier en mayo 08, 2023. Para
uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
CHAPTER 25 — Understanding and Treating Chronic Osteomyelitis 709

is the predominant cause of osteomyelitis in the adult popula-

Table 25.1 Estimated Number and Costs of tion. Between 38% and 67% of chronic osteomyelitis is
Infected Tibia Fractures Per Year for
reported to be caused by S. aureus.55 About 33% to 55% of
the United States
all S. aureus osteomyelitis cases can be traced back to
Estimated methicillin-resistant S. aureus (MRSA) strains.56,57 However,
Number Estimated the trend toward increasing rates of MRSA infections, in
of Closed Number general, has recently reversed, probably due to widely defined
and Open Infected preventive initiatives.58 Other important microbes implicated
Tibia Shaft Infection Tibia in causing osteomyelitis seen commonly in clinical practice
Fracturesa Rateb Fractures Costsc include Streptococcus spp., Bacteroides spp., coagulase-negative
Closed 46,000 2% 920 $47.2 M Staphylococcus spp., Corynebacteria spp., Klebsiella spp., Bacillus
spp., Enterococcus faecalis, Propionibacterium acnes, and the very
Open 8000 8.8% 700 $36.1 M
important pathogen Pseudomonas aeruginosa. Pseudomonas is
Total 54,000 1620 $83.3 M most commonly seen in injuries of the foot and lower leg.
In its chronic biofilm state, Pseudomonas hides perfectly in
a
US population of 318 million, incidence for tibial shaft fractures the body, with its biofilm biosphere often living in harmonious
of 17/100,000 and distribution of 85% of closed vs. 15% of existence with its host. Differences in the prevalence of certain
open fractures (Weiss et al., 2008). organisms may depend on the anatomical location of osteo-
b
SPRINT investigators, 2008. myelitis, the route of infection, host factors, and the regional
c
Based on costs of $51,364 per case (Thakore et al.).
origin of the outlined cases.54,59 However, we have seen many
From Alt V. Antimicrobial coated implants in trauma and
orthopaedics—a clinical review and risk-benefit analysis.
cases of certain microbes described as having a prevalence
Injury. 2017;48:599–607. in one part of the body (e.g., Propionibacterium around the
apocrine glands between the neck and breast line) that cause
pathogenic osteomyelitis in a far distant location of the body
(e.g., tibial osteomyelitis; see Fig. 25.4).
in the body has been directly related to a higher incidence Staphylococci are ubiquitous organisms and elements of the
of cardiac disease.48 natural skin flora. Trauma with disruption of the skin envelope
Patients with chronic osteomyelitis and chronic draining enables inoculation of soft and bony tissue. Because S. aureus
sinuses carry a low risk of malignant changes of the sinus is by far the most common bacteria causing osteomyelitis,
tract epithelium in 0.2% to 1.6% of cases, with squamous staphylococcal virulence factors besides biofilm itself have
cell carcinoma being the most common form of malignant been intensively addressed in clinical and experimental
transformation, which should be suspected in patients with research. First, adhesion factors expressed by S. aureus, such
the triad of elevated symptoms, foul discharge, and hemor- as fibronectin-binding proteins and collagen-binding proteins,
rhage.49,50 Chronic osteomyelitis in the elderly was also shown facilitate attachment to wounded tissue after inoculation has
to be associated with a significantly higher mortality risk taken place. In the case of implantation of biomaterials or
compared with controls without chronic osteomyelitis, with orthopaedic implants, extracellular matrix and plasma pro-
an incidence ratio of 2.29 (2.01 to 2.59) compared with 1.89 teins (fibronectin, collagen, vitronectin, fibrinogen, laminin,
(1.66 to 2.15) after adjusting for age, gender, comorbidities, thrombospondin, bone sialoprotein, elastin or von Willebrand
and monthly income.51 factor) rapidly cover foreign surfaces. Colonization of foreign
Furthermore, the psychosocial and economic consequences surfaces by adhesion factors against the host-derived protein
of long-term disability have a significant negative impact on layer, which covers the orthopaedic devices, can be regarded
the quality of life of patients52 suffering from chronic osteo- as the first step in biofilm formation. For the development
myelitis, including separation from family, loss of job, and of biofilms, intercellular adhesins are expressed, which
so forth, and these often represent the greatest toll on the enable the formation of cellular clusters.20 Second, factors
patient and greatest economic burden to society. It should that promote evasion from host defenses are relevant. S.
thus be quite apparent that the cost to society of chronic aureus protein A (SpA) is a surface protein that binds to
osteomyelitis represents a real health and social burden. the Fc region of immunoglobulin G (IgG), which prevents
the Fc regions of IgG from binding to the Fc receptors of
phagocytes. Besides this antiphagocytic effects of SpA, binding
to tumor necrosis factor receptor-1, which is expressed on
PATHOGENESIS
pre-osteoblastic cells, was shown to induce apoptosis and bone
loss. In addition, SpA binding to osteoblasts was demonstrated
CAUSATIVE ORGANISMS
to induce expression of receptor activator of nuclear factor
According to our best current knowledge, the leading cause kappa B ligand (RANKL) and secretion of proinflammatory
of osteomyelitis is bacterial infection. Hematogenous osteo- cytokines, leading to stimulation of osteoclastogenesis and
myelitis is typically monomicrobial in most cases, whereas in bone resorption.60 Third, the ability to gain intracellular
posttraumatic osteomyelitis after open fracture and exposure access to host cells is an important virulence factor. Both S.
to water, soil, foreign bodies, and skin flora, polymicrobial aureus and Staphylococcus epidermidis have been shown to invade
infection is likely.53 osteoblasts. Surface proteins, such as fibronectin-binding
By far, gram-positive aerobe (89%) pathogens are the most protein, allow staphylococci to complex with osteoblastic
frequent cause of bone infection, followed by gram-negative integrins, which leads to consecutive internalization. Thus
aerobes (45%) and anaerobes (16%).54 Staphylococcus aureus intracellular staphylococci are protected from host immunity

A
B
Fig. 25.1 Internalization of Staphylococcus aureus in osteoblast-like cells (arrows) in a cell-culture infection model with additional extracellular
clusters of S. aureus (arrowheads) examined by light microscopy (A). Division of the bacteria (arrows) within the osteoblast-like cell in transmission
electron microscopy (B).

and antibiotics.55 Finally, destructive capacities characterize with the occurrence of SCVs. In addition to their phenotype
staphylococcal virulence. Exotoxins attack host cells, and and reduced growth rate and metabolic characteristics, these
enzymes such as hydrolases degrade the extracellular matrix. SCVs do not produce virulence factors, which stimulate
This promotes bacterial invasion and tissue penetration.20 cytokine release and immune response. Different mechanisms,
Small colony variants (SCVs) were first described in 1910. such as low ATP levels, defective catalase activity, and depressed
According to their name, the most obvious feature is that electron transport activity, are responsible for decreased
they form colonies that are nearly one-tenth the size of colo- aminoglycoside uptake to the cell and may account for
nies created by wild-type bacteria. Intracellular survival as antibiotic resistance. The comparable slow growth, with its
well as the growth of S. aureus in eukaryotic cells, such as reduced cell-wall division in SCVs, is a reason for the inef-
osteoblasts, has been elucidated (Fig. 25.1).61 fectiveness of antibiotics that act on the cell wall. The
The intracellular invasion of the microbes enables them pathophysiologic significance became obvious after minimum
to avoid host innate and noninnate defense mechanisms inhibitory concentrations of aminoglycosides were found to
such as host antibody and phagocytic response. In doing so, be up to 16 times higher for SCVs compared with normal
they are hidden from all body defense mechanisms because colony types.64
they are no longer recognized as being foreign. Because One must note, though, that the clinical relevance of
nearly all antibiotics, except rifampin, used in clinical practice intracellular persistence of S. aureus as SCVs has yet to be
do not cross the eukaryotic cell membrane, they have no determined, and no true disease recurrence has been con-
effect on the SCVs because the host cells’ envelope shields firmed due to these intracellular SCVs. However, the sessile
the SCVs from such exposure.62 The SCVs then go into a phase of existence and intracellular hiding with similar
reduced metabolic state once they are intracellular. In essence, reduced growth and metabolic characteristics both clearly
they behave like the sessile phase of growth in a biofilm. represent defenses by the microbes that overwhelm our
With their reduced metabolic rate and greatly reduced current host defense mechanisms and therapeutic modalities
generational cycle, reduced alpha-toxin production by these in fighting them.
microbes has also been confirmed. Essentially, the SCVs are
trying to effectively coexist with the host cell they have invaded
ROLE OF FUNGAL AND OTHER PATHOGENS
because it is to their benefit to peacefully coexist with their
new host cell biosphere. More than 100,000 fungal species have already been described;
SCVs have been shown in a wide range of bacterial genera among them, 150 are known to be pathogenic to humans
and species, including S. aureus, S. epidermidis, Staphylococcus or animals. However, in immunocompetent patients,
capitis, P. aeruginosa, Burkholderia cepacia, Salmonella serovars, fungal osteomyelitis plays a tangential role compared with
Vibrio cholerae, Shigella spp., Brucella melitensis, Escherichia coli, bacteria-caused bone and joint infections. Nevertheless, for
Lactobacillus acidophilus, Serratia marcescens, and Neisseria gonor- immunocompromised patients, mycotic or parasitic bone
rhoeae. Besides osteomyelitis, SCVs can be evidenced in infections may have devastating consequences, which can
abscesses, soft tissue, the respiratory tract, and blood.63 be recognized by the mortality rate of patients suffering
Recrudescent or persistent infections have been associated from Aspergillus osteomyelitis, which is reported to be up

to 25%.65 As with any infectious disease, host factors play a fox tapeworm, is restricted to temperate regions of North
determining role in the pathogenesis. Risk factors for fungal America, Europe, and Asia. Compared with infestation of
infections are immunosuppression by disease or medication other organs (liver, 70%; lungs, 20%), bone hydatidosis is
(e.g., anti-tumor necrosis factor α), IV drug abuse, diabetes rare (1% to 2.5%). In 50% of all bony parasitosis, manifesta-
mellitus, HIV, organ transplantation, use of broad-spectrum tion is spinal.62,69
antibiotics, parenteral hyperalimentation, and the presence
of an indwelling catheter. In general, the paths of infections DEVELOPMENT OF A BIOFILM AND ROLE OF A
of fungal osteomyelitis are the same as for bacterial infection.
BIOFILM IN OSTEOMYELITIS
Hematogenous spread, contiguous infection after trauma,
surgery, or insertion of a joint prosthesis and infection due The term biofilm was introduced by J. W. Costerton70 in the
to vascular insufficiency have the potential to end up in early to mid-1980s. In treating osteomyelitis, it is quite helpful
fungal osteomyelitis. The most common fungal pathogens for the clinician to understand the evolution of a biofilm
for osteomyelitis are Candida species, which usually can be and its role in chronic-phase infections. This is so, as in the
found on the skin and mucous membranes in healthy people. words of the first author, “to beat a microbe, one must first
Candida osteomyelitis is most frequently caused by Candida be able to think like one.” The point of this is that if one
albicans and is found in the vertebrae, sternum, ribs, femur, can learn to understand what a microbe is doing and why
hips, facial bones, humerus, foot, ankle, and tibia. The second it is doing it in a host, then it becomes a bit easier to treat
most common fungal pathogens for osteomyelitis are Aspergil- the problem. For this reason, an explanation of the maturation
lus species (A. fumigatus, A. flavus., A. niger, A. terreus), which of an infection in bone is warranted.
are ubiquitous saprophytic molds. Contiguous spread from After the initial inoculation of bone or an implant with a
pulmonary or sinus infections is described, but hematogenous free-floating planktonic cell, adhesion of such cells onto the
spread occurs in adults as well. Thus the most frequent bone, soft tissue, or implant surface begins. One common
location is logically the vertebrae. However, as with Candida theme must exist for such adhesion and infection maturation,
species, the growth of Aspergillus species in blood cultures and that is the existence or development of nonviable or
is rare.66 necrotic tissue/bone or the existence of a nonliving foreign
Coccidiomycosis is an endemic fungal disease in the substance. Without this, an infection nidus cannot develop a
southwestern United States, Mexico, and some areas of Central “foothold.” The act of adherence then evolves from a revers-
and South America. It is caused by Coccidioides immitis (endemic ible to a nonreversible phenomenon, and biofilm formation
to California) or Coccidioides posadasii (endemic to other begins. In order for the bacteria to create this “fortress,” they
regions). The estimated incidence in the United States has need material for construction. A biofilm’s building blocks
risen to approximately 150,000/per year as a result of popula- are composed of proteins, mucopolysaccharides, and nucleic
tion increase in the endemic regions. After inhalation of acids. These three components represent the material of dead
arthrospores, about 40% of the infected patients develop cells, so there must be a component of controlled prokaryotic
clinical symptoms most often resembling bronchitis or cell death allowing for material to construct the structure.
community-acquired pneumonia. Extrapulmonary manifesta- The microbes are now beginning to act like a multicellular
tion is uncommon (~0.5% to 5%). It depends mainly on the organism colony; they are communicating with one another
immune status of the patients (20% to 50% dissemination for this highly organized process to occur. The colony soon
in immunocompromised patients). However, different begins exopolysaccharide production to further construct
incidences of extrapulmonary dissemination are reported this highly structured fortress it inhabits (Fig. 25.2).
for patients of Caucasian ancestry (0.5%), with several-fold- Eventually, a complex, hydrophobic, multichanneled
higher incidences in patients of African and Filipino ancestry. structure is constructed. Unfortunately, no one to date has
The skin, the central nervous system, and the musculoskeletal been able to show in real time how long the process from
system are the most frequently involved extrapulmonary organ bacterial adhesion to the formation of a mature biofilm takes.
systems. Favored sites of bone infection are the ends of the These structures are truly ubiquitous in nature and are integral
long bones and, due to the hematogenous dissemination, to how microbes interact with nature.71 They are found in
the spine and the pelvis.67,68 In clinical practice, though, the a range of environments, from rocks in streams to heat
first author has seen Coccidiomycosis osteomyelitis in most exchangers at the bottom of the ocean, to medical device
bones of the body, including all long bones and bones of implants. Over the past 25 years, their importance in medical
the hand and feet. It is generally slow growing but destructive infections has become continually more appreciated, such
in nature, with an inflammatory response much less vigorous that the US National Institute of Health has announced,
than that seen in bacterial cases. “Biofilms are medically important, accounting for over 80%
Other unusual pathogens, such as Histoplasma, Blastomyces, of infections in the body” (program announcements PA-03-047
and Cryptococcus or the even less common Sporothrix, Rhizopus, and PA-06-537).71
Peteriellidum, Trichophyton, Acremonium, and Scedosporium species, Once in this biofilm complex, the microbial colony cell
may cause mycotic osteomyelitis. All of them either spread lines morph into a sessile phase of growth. The hallmark
hematogenous to the bone or as contiguous infection, both of this phase is their markedly reduced metabolic rate and
promoted by reduced immunocompetence of the host.66 increased generational cycle, with a resultant decrease in
Parasitosis with skeletal involvement in terms of osteomy- susceptibility to antibiotics.72 This decreased susceptibility to
elitis is also rare. Usually, Echinococcus tapeworms cause parasitic antibiotics has been shown to be altered by a factor of as much
osteomyelitis, mostly E. granulosus and E. multilocularis. as 103, making the measurements of minimum inhibitory
Whereas E. granulosus, the dog tapeworm, has a worldwide concentration (MIC) virtually meaningless in determining a
geographic distribution, E. multilocularis, also known as the given antibiotic’s efficacy for treatment in such situations.73

A C
Fig. 25.2 Biofilm formation within the tibia intramedullary canal in a rabbit bone infection model with signs of chronic infection of the cortical
and intramedullary parts by light microscopy (A). Magnification of the box area demonstrating colonies of S. aureus around bone sequesters
(B). Higher magnification shows biofilm formation (arrow) around the bacteria and bacterial infiltration of the sequester (double arrow) (C).

Thus the biofilm complex represents a huge barrier to continually repopulate the cell-line colony of the biofilm in
systemic antibiotic therapy in the treatment of such infec- the form of planktonic or sessile-phase cells.72–74
tions. This is true for at least four reasons.74 The first is Two other barriers exist to the efficacy of antibiotics in
the highly structured, hydrophobic nature of the biofilm the treatment of biofilms in chronic osteomyelitis. One of
complex. This inherently inhibits the free flow of antibiotics these is the generational cycle of microbial cell lines versus
in serum to penetrate and interact with the sessile-cell- their human hosts (Table 25.2). One can appreciate that
phase microbes. The three-dimensional semi-impermeable their rapid growth and generational cycle allow no competi-
matrix also serves as a barrier such that the microbes can tion in a microbe’s ability to mutate and adapt to changes
actually hide within the “primordial sludge” of this biofilm in the organism’s environment as compared with that of
matrix.74 The third reason is, as mentioned previously, the their human host.
sessile phase of growth for the microbial population in the The other advantage of a biofilm colony is that it possesses
biofilm. Their markedly reduced metabolic rate accounts a veritable genetic library at its disposal. This concept has
for much of this effect because antibiotics are designed to been elucidated by Garth Ehrlich and his work on the dis-
work in cells in a rapidly growing planktonic state. Last, tributed genome hypothesis.75–77 To understand this, one
the existence of persister cells in the colony represents the must first realize that in nature, just as in infections in humans,
final barrier. most infections in which a biofilm has developed are com-
Persister cells are estimated to represent approximately posed of multibacterial species.78 This makes conceptual
1% of the biofilm colony’s population. These are microbial sense, especially in the world of trauma, where an open
cells with the same genotype as the cells of the native colony fracture then leads to chronic osteomyelitis. There is no
that exist in essentially a dormant state. These cells are hence reason to believe that just a single organism species would
antibiotic tolerant (not resistant, an important distinction) alone colonize such a wound and solely grow and form a
to all currently described antibiotics. The persister cells biofilm with no other organisms in the environment being
represent a fresh pool of multidrug-tolerant cells that can present and joining in. In the study by Palmer et al.,78 the

Table 25.2 Organism Generational Cycles

Generational Cycles of Bacterial Cell Phases Compared

With the Human Cycle
Organism Generation Cycle

Bacteria 20–30 minutes

(planktonic)
Prokaryotic Lysis of cell Free DNA
Bacteria Hours to 1 day organism wall and segments
(sessile, in biofilm) escape of DNA
Humans 20–30 years

Reprinted with permission from Lowenberg DW, Watson JT,

Levin LS. Advances in the understanding and treatment of
musculoskeletal infections. AAOS Instr Course Lect.
2015;64:37–49.

authors showed that in nonunions, not only were 88% infected Adherence and Incorporation of
or colonized, but also at least 62% were multiorganism in transport of free free DNA into
nature. This study tested only 188 different microbes, and DNA in to colony colony microbe
surely more than this number exist in our world that can microbe
act as pathogens. Fig. 25.3 A schematic representation of the mechanism of genetic
A biofilm is composed of not just mucopolysaccharides transformation that occurs within a biofilm to incorporate “banked”
and proteins but also nucleic acids. These nucleic acids in free DNA into the genome of a microbe. (Courtesy, David Lowenberg,
the form of DNA are found in the biofilm. This represents MD.)
part of the cell debris that lives in the biofilm and serves as
a “genetic library,” if you will, for the active cell colony to
use and incorporate for traits they may require over time to
help protect the biosphere colony. If the colony deems it
necessary to incorporate resistance to a particular antibiotic
in which it has that DNA trait stored, it can simply incorporate The same thinking can apply when acute septicemia
this trait by transformation into its bacterial genome develops after reactivation of an underlying chronic osteo-
(Fig. 25.3). myelitis. The only options to explain this remain an acute
This has, in fact, been shown to occur and hence represents change in the biofilm colony whereby the colony releases
a “supragenome library” for the biofilm colony to use as it large volumes of planktonic cells into the host environment
deems necessary.74 One can now better appreciate the power or a profound difference in the host’s immune status such
of a biofilm colony and how it actually behaves as a multi- that the homeostatic balance is disturbed. Something, though,
cellular entity rather than what we have classically thought invariably becomes upended in the balance between these
of as bacteria being single-celled organisms. two apparent “symbiotic biospheres” to cause the change in
New research has also shown that not only are the majority balance. To this point, the details of the tipping factors remain
of infection-causing biofilms polymicrobial but that a poly- unknown.
microbial biofilm is in fact more virulent and produces a
more robust biofilm.79 Such studies have also shown that
such biofilms have a thicker matrix as part of their defense TYPES AND CLASSIFICATION
mechanism. OF OSTEOMYELITIS
When one thinks about it, once a biofilm becomes estab-
lished in the host, it is to the biofilm colony’s advantage to In treating cases of osteomyelitis, it is imperative to character-
peacefully coexist with the host. If the colony continually ize the type and extent of osteomyelitis one is addressing. It
releases planktonic cells into the host, it is essentially “pol- is vital that the clinician differentiate not just the chronicity
luting its world” and causing its own eventual destruction. but also such nuances as the location at the bone segment
Therefore a smart colony tries to symbiotically coexist with as well as in the bone. This must also be incorporated into
the host. This is the reason that cases of chronic osteomyelitis the host. We have found that defining the host/patient is
can exist in a host for years with no signs whatsoever of also imperative in the effective treatment of this condition
infection being present. However, they can later resurface (Box 25.1).
for often no apparent reason. It has been the first author’s The implications of whether an infection of bone is acute
observation, though, that often an inciting event that alters or chronic become quite important for several reasons. For
host immunology and physiology tends to precede such the sake of clarification, we shall define acute infection as
recurrences (Fig. 25.4). those in which the primary cell type is the planktonic phase

C
D

E
Fig. 25.4 An 80-year-old female in good health presented with a draining left distal lateral thigh sinus tract of 2 weeks’ duration that spontane-
ously developed after a battle with the flu. On past medical history, the patient had suffered from hematogenous left distal femoral osteomyelitis
at age 14. This had been treated at that time with an open débridement. By history, she was also treated with penicillin in the year of its release
in 1943. She healed uneventfully and remained completely asymptomatic until this presentation. (A) Photograph of left lateral thigh showing
draining sinus tract. (B) Anteroposterior (AP) radiograph of left distal femur. (C) Lateral radiograph of left distal femur. (D) Intraoperative photograph
of elliptical femoral window and débrided intramedullary canal. (E) Intramedullary sequestrum excised at the time of débridement.

F G

H I

Fig. 25.4, cont’d (F) Post-op AP radiograph showing dead-space management with antibiotic bead pouch and stabilization with antibiotic
bridge plate to prevent fracture. (G) Lateral postoperative radiograph. (H) AP radiograph after antibiotic bead and antibiotic bridge plate removal
with bone grafting of defect and bridge plating. (I) Lateral radiograph after grafting and plating. Continued

J K

Fig. 25.4, cont’d (J) AP radiograph 5 months after grafting and plating. The patient is ambulating independently without pain, with no evidence
of recurrent infection. (K) Lateral radiograph 5 months after grafting and plating. (Courtesy David W. Lowenberg, MD.)

It is well recognized that such cases of acute hematogenous

Box 25.1 Characterization of osteomyelitis in children are successfully treated with appropri-
Osteomyelitic Segment ate systemic antibiotic administration. This difference in the
microbial cell phase combined with the impermeable,
1. Acute vs. chronic infection hydrophobic nature of a mature biofilm represents the key
2. Hematogenous vs. direct inoculation
delineator of acute versus chronic osteomyelitis. This chapter
3. Location in the bone
a. Epiphyseal vs. metaphyseal vs. diaphyseal focuses on the characterization and treatment of chronic
b. Mixed location osteomyelitis.
c. Can an accompanying joint be preserved? When one encounters a case of chronic osteomyelitis, it is
4. Health of the surrounding soft tissue envelope helpful to try to determine the cause. Especially in trauma,
5. Cierny-Mader type of osteomyelitis the cause is more often than not due to the injury sustained
6. Cierny-Mader host classification by the patient. This can be because of an open fracture with
7. Accompanying bony deformity and/or axial deformity direct introduction of a microbe into the bone or because
of surgery performed to help reduce and stabilize the bone.
Courtesy David W. Lowenberg, MD. This then becomes a rather straightforward “cause and effect.”
However, on occasion, one encounters a patient with a chronic
nidus of osteomyelitis with no antecedent trauma or local
surgery to explain this. In these cases, it is more likely than
of microbial cell growth at the site of the infection. Such not that the microbe was spread hematogenously. In the
infections are present for a finite and short duration. A mature adult population, the clinician should then try to localize
biofilm has not had a chance to fully develop, and the cells the source of such seeding of the bone or an immunologic
have not had the opportunity to convert to a sessile phase reason why this has occurred (Fig. 25.5). More often than
of growth. In fact, no one knows exactly how many days or not, a reason can be established, and this is important so as
weeks this conversion takes. A typical example of an acute to try to optimize the host condition to prevent further such
osteomyelitis would be that of the initial presentation of a incidences of seeding and spread. Unfortunately, though,
hematogenous osteomyelitis, as typically seen in young there are times when no reason or source can be established.
children, with an end arteriolar location in the metaphyseal/ One wants to factor in the location in a long bone in
epiphyseal region of the long bones. This matters because characterizing the case of the chronic osteomyelitis in ques-
it directly affects the treatment that is provided to the patient. tion. This is because it directly affects the treatment rendered

to the patient. An exclusively diaphyseal location often offers treatment option. One must also decide in these periarticular
more treatment options to the surgeon for the constructive instances whether joint replacement or arthrodesis must be
pathway taken after infection eradication. Choices can, factored into the treatment algorithm.
unfortunately, be more limited when one is faced with a As orthopaedic surgeons, we too often become solely
purely epiphyseal or metaphyseal-epiphyseal osteomyelitis. focused on the bone and do not give enough attention to
Taking these factors into consideration before the initiation the surrounding soft tissue envelope. When dealing with
of treatment is imperative so that a reasonable treatment cases of chronic osteomyelitis, the surrounding soft tissue
plan can be established. If this is then deemed nonrecon- envelope is adversely affected. This is especially true if the
structable, then amputation might be a more reasonable underlying cause was due to trauma. One needs a healthy

Fig. 25.5 A 68-year-old male with cutaneous lymphoma started on a new targeted chemotherapeutic regimen. Two weeks after infusion, the
patient became septicemic with a urinary tract infection and progressive and severe left thigh pain. Urine cultures grew Escherichia coli.
Radiographs of his left femur revealed subtle midshaft endosteal scalloping. (A) Anteroposterior (AP) radiograph of the left femur; notice endosteal
changes at the midshaft. (B) Lateral radiograph of the left femur with same endosteal changes. (C) Coronal T1 magnetic resonance imaging
(MRI) of left femoral shaft showing intramedullary changes consistent with osteomyelitis. Continued

D E

Fig. 25.5, cont’d (D) Coronal T2 fat-suppression MRI of corollary femoral shaft segment. (E) Sagittal short tau inversion recovery (STIR) MRI
of corollary femoral shaft segment. These imaging studies combined with the clinical picture were highly consistent with hematogenous
Cierny-Mader type 1 osteomyelitis. Because of other medical issues, referral for treatment was delayed 6 weeks. He was then seen and treated
with intramedullary débridement by gentle reaming and washing out of the intramedullary canal. A custom antibiotic nail was then placed for
dead-space management and local antibiotic delivery. All intraoperative cultures grew E. coli. (Courtesy David W. Lowenberg, MD.)

Table 25.3 Cierny-Mader Classification of Chronic Osteomyelitis

Stage Anatomic Type Typical Etiology Treatment

1 Medullary Infected intramedullary nail Removal of the infected implant and

isolated intramedullary débridement

2 Superficial; no full-thickness Chronic wound, leading to colonization Remove layers of infected bone until
involvement of cortex and focal involvement of a superficial viable bone is identified
area of bone under the wound

3 Full-thickness involvement of a cortical Direct trauma with resultant Noninvolved bone is present at same
segment of bone; endosteum is devascularization and seeding of the axial level, so the osteomyelitic portion
involved, implying intramedullary bone can be excised without compromising
spread skeletal stability

4 Infection is permeative, involving a Major devascularization with Resection leads to a segmental or

segmental portion of the bone colonization of the bone near-segmental defect, resulting in loss
of limb stability

Printed with permission from David W. Lowenberg, MD

soft tissue envelope for the eradication and reconstruction 1980s and early 1990s by the late George Cierny and John
of the area of osteomyelitis. An atrophic or dystrophic soft Mader. It was based on the observation of a large number of
tissue envelope will provide poor blood supply to the area cases of chronic osteomyelitis and was developed not just to
of bony reconstruction and can often lead to wound break- categorize the condition but also to help guide treatment.
down and resultant recurrent infection. It is therefore The classification scheme is quite easy and intuitive. Four
imperative that the clinician not just recognize an impaired stages of osteomyelitis are described, but they do not repre-
envelope but also be knowledgeable on the most appropriate sent a direct continuum in the depth of bone involvement
method of soft tissue management and reconstruction. (Table 25.3).
The most widely used and accepted classification of Stage 1 C-M osteomyelitis represents a pure intramedullary
long bone osteomyelitis remains the Cierny-Mader (C-M) endosteal process. This is most commonly iatrogenic in nature
classification scheme.80 This was developed primarily in the and is caused by an infected intramedullary rod. It is also

Table 25.4 Cierny-Mader Physiologic Host Classification

Type Infection Status Perpetuating Factors Treatment

A Normal physiologic response Little or no systemic or local No contraindications to surgical treatment

compromise

B (local) Locally active Prior trauma, or surgery to area; Consider healing potential of soft tissues
Impairment of response chronic sinus; free flap; impaired and bone, consider adjunctive measures
local vascular supply

B (systemic) Systemically active Diabetes, immunosuppression, Treat correctable metabolic/nutritional

Impairment of response vascular, or metabolic disease abnormalities first

C Severe infection Severe systemic compromise and Suppressive treatment or amputation

stressors

Reprinted with permission from Lowenberg DW. Nonunions, malunions and osteomyelitis, in Boyer MI (ed): AAOS Comprehensive
Orthopaedic Review, ed. 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2014.

seen by hematogenous spread in patients with immunode- to heal localized to the limb at and surrounding the site of
ficiency often caused by a chronic disease state (e.g., cancer, osteomyelitis (Fig. 25.6).
autoimmune disease). It is moderately common in nature.
Stages 2 through 4 represent a continuum in the depth of
disease, from outside to inside the bone segment. Stage 2
DIAGNOSTICS
involves the periosteal side of the bone with no extension
to the endosteal surface and medullary canal. In fact, it
APPROPRIATE TESTS
represents the rarest form of osteomyelitis encountered by
the first author. Stage 3 involves a full-thickness region of Diagnosis of osteomyelitis needs a combination of good clini-
infected/necrotic bone that goes from the periosteal surface cal skills and proper diagnostic studies. Clinical suspicion is
into the medullary canal. It does not, though, represent a key to early diagnosis and the basis for treatment success. A
segmental defect with full circumferential involvement. This detailed history of disease is of paramount importance. This
means circumferential resection in treatment is not necessary. not only facilitates correct diagnosis but also is of relevance
In the first author’s experience, this represents the most for treatment decisions and complication assessment.
common stage of chronic osteomyelitis encountered in clinical Patients’ complaints often include the cardinal symptoms
practice. Stage 4 osteomyelitis represents a full segmental of infection, such as rubor, calor, dolor, tumor, and functio
portion of bone involvement. Resection of this leaves a laesa. In addition, low-grade fever may occur as well as
segmental defect in the affected bone. The quintessential drainage around the area of trauma, surgery, or wound
example and definition of this would be an infected diaphyseal infection.81 Vague and generalized symptoms are often
nonunion. Infected nonunions of the diaphysis therefore reported by patients suffering from chronic osteomyelitis.
are stage 4 by definition because resection of the nonunion Furthermore, cyclic pain increasing with fever is described
is then absolutely required. One can appreciate, then, that as well as pain relief when the abscess cavity decompresses
this staging scheme helps define treatment—and hence its through a fistula.82 A history of past trauma and prior sur-
value in clinical practice. geries has to be evaluated. The mechanism of injury and
Cierny and Mader were also quite wise in realizing that resultant treatment is of importance in better describing
the condition of the host plays an equally important role the pathophysiology of the lesion. Whenever possible, the
in the staging of the disease for treatment. For this reason, results of prior microbiologic diagnostics and antibiotics for
they also staged the host as to how able physiologically treatment of past bone and soft tissue infections should be
(both locally and systemically) the patient was to fight the obtained. Comorbidities play a crucial role in the host’s soft
disease and survive the treatment provided (Table 25.4). tissue healing and immune response and in the outcome of
In fact, they learned that in some patients (type C hosts), the planned therapy. Furthermore, systemic diseases such as
the treatment could be worse than the chronic disease. cardiovascular disease, chronic kidney disease, diabetes, and
In such cases, amputation, or simply living with the immune deficiency and their sequelae, such as edema of
chronic infection, became the resultant preferred treatment the extremities and micro- and macrovascular impairment,
method. have to be considered in selecting the optimal therapeutic
One can see that various permutations exist in the staging approach for the patient, which ranges from limb salvage
of a patient with osteomyelitis, which has great similarity to to amputation of an extremity.83
the staging systems used in oncology. For instance, a patient The physical examination starts with inspection. Swelling,
might be diagnosed with a stage 3B (local) chronic osteo- erythema, open wounds, and draining sinuses indicate infec-
myelitis of the midshaft of the tibia. This defines a full- tion. However, the distinction between soft tissue infection
thickness, noncircumferential osteomyelitic segment of the and osteomyelitis is difficult.84 Inspection for tenderness,
tibia in a patient with impaired local physiology and ability swelling, and structural abnormalities should be done. Trivial

A B

C D
Fig. 25.6 A 69-year-old male who suffered a gunshot wound 40 years prior. He had been treated with local wound care and casting at the
time in Vietnam. The patient now presented with knee pain. He was in good health, with just slight hypertension and no peripheral arterial
disease. (A) Photograph showing the impaired soft tissue envelope and chronic sinus tract (Cierny-Mader type Blocal host). (B) Anteroposterior
(AP) view of left proximal tibia. (C) Lateral view of left tibia. (D) AP mechanical axis weight-bearing view of both lower extremities showing
resultant mechanical axis deviation and medial compartment degenerative disease. The patient presented due to his medial knee pain secondary
to arthritic disease. (Courtesy David W. Lowenberg, MD.)

skin lesions may be sinus tracts extending to bone. For diabetic can be foreign microorganisms or other biologic debris. It
patients, the probe-to-bone test is an accurate and cheap is very important to understand that in many if not most
method to determine osteomyelitis in diabetic foot syndrome.85 cases of chronic osteomyelitis, the biofilm colony does not
Often, the extent of infection is underestimated, and especially release planktonic cells, so no debris or foreign microorgan-
in patients with diabetes, signs and symptoms may be disguised isms are released in the systemic circulation for the host to
by vascular disease and neuropathy. attack. Hence, the CRP remains normal.
Unfortunately, none of the signs and symptoms described
is pathognomic for osteomyelitis. The differential diagnosis
VALUE OF CULTURES
includes both benign and malignant tumors, benign cysts,
metabolic and inheritable bone diseases, sickle cell disease, Classically, the cornerstone of appropriate antimicrobial
bone infarcts, hemoglobinopathies, and foreign-body reac- treatment of osteomyelitis is to identify the causative micro-
tions. These therefore require further diagnostic workup.86 organism. The most effective method involves obtaining deep
tissue samples of the affected bone and soft tissue. Harvesting
and cultivating swabs of open sinus tracts and drainage fluid
ROLE OF INFLAMMATORY INDICES
is easy to perform but will give misleading results because
Standard laboratory tests for diagnosis of osteomyelitis include opportunistic organisms often coexist on the peripheral
white blood cell (WBC) count, serum C-reactive protein superficial sites and sinus tract and in fact do not represent
(CRP) levels, and erythrocyte sedimentation rate (ESR). the actual deep organism responsible. A prospective study
These laboratory values are rather nonspecific for bone including 100 patients compared cultures from nonbone
infection versus a host of other entities. Hence, screening specimens with deep bone cultures. In only 30% of these
for osteomyelitis by laboratory tests alone is of no real value. patients did the superficial cultures align with the deep bone
The value of these studies exists if they are elevated at the cultures.54 To avoid false-negative results, obtaining cultures
time of diagnosis of the infection because they can then be before commencing antimicrobial treatment is recommended.
followed as a barometer of the efficacy of treatment. For Furthermore, several intraoperative biopsies should be taken
infected nonunions, the highest sensitivity and specificity because the majority of the cell line in the biofilm of chronic
were reported for CRP levels, 60% (95% confidence interval osteomyelitis is in a sessile phase of growth. These are gener-
[CI], 42% to 76%) and 86% (95% CI, 42% to 99%), respec- ally hard to grow and represent one of the reasons why there
tively, compared with ESR, WBC count, and interleukin-6 is such a high false-negative rate of positive cultures in such
(IL-6). However, those experienced in the care and treatment cases.90 Moreover, the culture itself may be the reason for
of osteomyelitis can confirm that elevated inflammatory false-negative results. Inability to culture fastidious pathogens
markers are present in at most 50% of such cases of chronic may be due to the lack of an ideal medium for the culture of
osteomyelitis. Cumulative use of biomarkers (ESR, CRP, WBC many organisms and the fact that we cannot culture the vast
count, IL-6) shows a reliable prediction probability, but all majority of microbes that exist on earth due to the lack of an
four elevated parameters are rare in patients with infected ideal medium on which to culture all bacteria. Mycobacterial,
nonunions. Nonetheless, 77.8% of patients with negative anaerobic, fungal, and parasitic microorganisms are possible
results in all four parameters suffer from infected non- reasons for false-negative results as well. Hence, cultures
union.87,88 Therefore a more stringent and specific laboratory should be specially processed if commonly cultured microbes
test for osteomyelitis is needed. Serum procalcitonin (PCT) are not detectable and the clinical appearance indicates
levels, an indicator usually used for systemic bacterial infec- infection with these other microbial entities.20 When osteo-
tions, such as bacterial meningitis, septic shock, bacteremia, myelitis is apparent with indwelling implants, sonication of
and pyelonephritis, were reported to have similar diagnostic the explanted hardware should be considered because when
performance to diagnose diabetic foot osteomyelitis compared carried out, this has been shown to increase the culture yield
with the diagnostic performance of serum CRP levels.89 PCT by releasing adherent organisms out of the biofilm.91 In this
sensitivity and specificity were reported to be 67% (95% CI, regard, the biofilm bacteria themselves may be a reason for
37% to 88%) and 90% (95% CI, 78% to 96%), respectively, negative culture results. Hence, culture-independent methods,
for the diagnosis of osteomyelitis and septic arthritis with a such as detection methods based on polymerase chain reaction
PCT test kit with a functional sensitivity of 0.5 ng/mL. Further (PCR), are more accurate for diagnosis in culture-negative
studies with even more sensitive PCT assays may improve the cases and possibly in all cases in the future to better delineate
performance of PCT tests in the identification of osteomy- the multispecies nature of many of these infections.78
elitis,87 but as yet, this has not been found to be a useful tool Tissue specimens of bone and chronic fistula should be
in clinical practice. examined histopathologically. More than five neutrophils
It is important that clinicians understand the meaning of per high-power field is suggestive of infection (sensitivity of
inflammatory indices and what they are actually measuring. 43% to 84%; specificity of 93% to 97%); visualization of
The ESR is an old test that is quite nonspecific. It simply granulomatous lesions by Ziehl-Neelsen staining enables
measures the rate at which red blood cells fall out of solution diagnosis of mycobacterial infection earlier than culture.20
(settle with gravity). This rate is directly affected by the amount
of protein in the host’s serum—the higher the amount of
DNA ANALYSIS
floating protein, the quicker the rate of settling of the red
blood cells. PCR-based molecular diagnostic methods were introduced
CRP represents not a single compound but rather at least to improve the confirmation or exclusion of infection over
20 different proteins. Each of these proteins is involved in the past 10 years. They are highly sensitive for chronic infec-
the digestion of substances deemed foreign to the host. These tion diagnosis. The technique of PCR was developed by Nobel

Prize–winning Kary Mullis in 1983. The technique allows for A promising technique, which is not a nucleic acid–based
the replication and magnification of small quantities of nucleic method, is matrix-assisted laser desorption ionization coupled
acid found at the time of biopsy from tissue.92 The techniques with time-of-flight analysis mass spectrometry (MALDI-TOF/
for this have been expanded and improved and now represent MS). Soft laser ionization of intact bacteria or bacteria extract
a valuable tool in the detection of a host of microbes, especially is used to detect a bacterial species’ unique protein and
those that are fastidious and slow growing or difficult to grow peptide surface by mass spectrometry.103 These fingerprints—
in the lab.93 For osteomyelitis, the usefulness of PCR amplifica- each bacteria species produces a different spectrum—allows
tion has been demonstrated especially in culture-negative one to theoretically identify microorganisms in a cheap,
osteomyelitis.94,95 However, in the evaluation of musculoskeletal reliable, and fast manner.104 Recently, several case reports of
infections, PCR is currently not a standard diagnostic tool. osteomyelitis with uncommon pathogens detected by MALDI-
Because of PCR’s potential, basic PCR techniques should be TOF/MS were published.105–108
considered in the future. Recently, a combination of PCR with mass spectrometry
For detecting bacterial infection, broad-range PCR acts as as described for PCR electrospray ionization mass spectrometry
a universal detection system. Primers directed against the 16S (PCR-ESI/MS) has been shown to combine fast detection
ribosomal RNA gene sequence, which is an evolutionarily of the presence of infection, the identity of the pathogen,
conserved gene exclusively existent in almost all bacteria, are and resistance markers in PJI, but it has not yet become
used for this method. In the case of a positive result, the PCR practice in the diagnosis of osteomyelitis.109
product is sequenced directly and compared with bacterial
DNA sequences of known species in databases. The drawbacks IMAGING STUDIES AND NUCLEAR
of this method are false-positive results using nonspecific
MEDICINE STUDIES
PCR primers detecting bacterial contamination and time-
consuming sequence analysis and database comparison.96 For chronic osteomyelitis as well as in daily orthopaedic
Pathogen-specific PCR enables a faster and more sensitive practice, radiographic imaging remains the cornerstone for
identification of microorganisms. Assays probing only for diagnosis and screening of bone pathology, including the
DNA from a certain number of species known to cause diagnosis of osteomyelitis.
infections allow direct detection of both the presence and If osteomyelitis is suspected, plain radiographs should be
identity of a pathogen. Especially for slow-growing bacteria, performed. The benefits of conventional radiography are
pathogen-specific PCR offers a reliable diagnostic tool. its widespread availability, low cost, and low radiation exposure.
Furthermore, antimicrobial resistance profiling is possible Plain radiographs remain the most accessible and economical
with direct detection of resistance genes. For example, PCR- tool in the initial screening for bone infection and other
based detection has been established in clinical diagnostics bone pathology. Periosteal reaction, cortical erosion, focal
for resistance genes, such as the mecA gene in MRSA and osteopenia, osteolysis, and endosteal scalloping can be
the rpoB gene for rifampicin resistance in M. tuberculosis.93 revealed by plain radiographs.110 Characteristic features of
There has been a fear that after treatment with antibiotics, subacute or chronic osteomyelitis may be demonstrated by
dead bacterial cells may remain in the host patient at the conventional radiography, such as involucrum, which is a
site of prior infection. The fear has been that this could lead layer of new bone growth outside the focus of infection;
to subsequent false-positive results for infection when utilizing sequestrum, which is a piece of dead bone separated from
the PCR technique. However, this has actually not been found viable bone by surrounding granulation tissue; and cloaca,
to be the case, and research has suggested that free microbial which is an opening in an involucrum allowing drainage of
DNA in a host wound is actually digested and removed in a purulent and necrotic material.111 However, lytic changes are
matter of days. Also, dyes such as ethidium bromide have usually not detected until at least 50% to 75% of the bone
been used to remove DNA from cells lacking cell-wall integrity. matrix is destroyed.112 Signs of septic arthritis, such as joint
However, complete inhibition of replication of dead bacterial gap narrowing and cortical erosion, as well as soft tissue
cell DNA is not possible. Therefore reverse-transcriptase PCR abnormalities such as swelling, radiolucent streaks, and
has been introduced to detect RNA, which has a shorter periostitis, may provide additional information. However,
half-life, degrading rapidly after bacteria cell death. The use although the sensitivity and specificity of plain radiographs
of messenger RNA and ribosomal RNA for quantitative are reported to be 60% and 67%, respectively, plain radio-
reverse-transcriptase PCR has been reported to be used for graphs are sometimes not suited as an isolated imaging
the determination of viable bacteria load, thus minimizing study.113
false-positive results after antibiotic therapy.97,98 Computed tomography (CT) provides the most detailed
Fluorescence in situ hybridization (FISH) is another images of cortical bone. Sequestra and intraosseous fistula
molecular biologic nucleic acid–based method for the detec- are thus clearly identified. Furthermore, high-resolution CT
tion of nucleic acids (DNA and RNA). A labeled comple- with sagittal and coronal reconstructions can accurately help
mentary DNA, RNA, or modified nucleic acid probe binds define the C-M stage of the osteomyelitic lesion, and the
to complementary DNA or RNA sequences. This enables first author finds this to be the most sensitive tool in the
localization of DNA and RNA in tissue samples, which is staging of such lesions. Periosteal reaction, degree of intra-
used for a broad field of diagnostic applications in oncology, medullary involvement, and accompanying soft tissue infiltra-
prenatal screening, and naturally infectious diseases.99–101 For tion can accurately be determined with this imaging study.
osteomyelitis, detection of S. aureus was shown for the first Analogous to gas within abscesses, intramedullary gas is best
time by FISH in a rabbit model of osteomyelitis.102 In the detected with CT. Nevertheless, gas formation, being a highly
future, clinical studies may clarify its significance as a diag- specific feature of osteomyelitis, is an uncommon finding.
nostic tool in clinical practice. In the case of the presence of implants, CT facilitates operative

planning and guides biopsies. For treatment monitoring, scintigraphy include general hematogenous osteomyelitis
CT enables gauging the amount of bony consolidation in and prosthetic joint infections. This may explain the reported
bone healing.111 high diagnostic accuracy. Because there is, unfortunately, a
Currently, magnetic resonance imaging (MRI) is a wide- lack of reliable studies on the accuracy of WBC scintigraphy
spread diagnostic tool with the benefit of differentiation in chronic osteomyelitis, it is not worth it to expose the
between bone and soft tissue, bone marrow involvement, patient to this elaborate examination.
and early detection of osteomyelitis. T1-weighted fast-spin Hybrid procedures combining nuclear medicine and
echo shows a low signal, whereas T2-weighted images are radiologic techniques show the efforts to increase the diag-
characterized by high signals in acute osteomyelitis. Although nostic value of nuclear medicine studies. In addition to the
chronic osteomyelitis shows a higher variability in MRI due combination of TPBS and WBC scintigraphy with single-
to its activation state, chronic osteomyelitis reveals a similar photon emission computed tomography (SPECT)/CT,
18
picture. Short tau inversion recovery (STIR) sequences F-fluorodeoxyglucose positron emission tomography
characterized by fat suppression show typically increased fluid (FDG-PET)/CT is a more commonly performed hybrid
signals in involved bone and soft tissues.111 Intravenous procedure but still outside the normal clinical routine.
application of gadolinium contrast enhances detected signals Leucocytes use glucose as an energy source. Therefore
in areas of vascularized inflammation, whereas nonvascularized radioactively labeled 18F-FDG enriches in sites of high meta-
areas such as sequestra lack enhancement by gadolinium bolic activity, such as infection and inflammation, which is
contrast application. Nonetheless, distinguishing osteomyelitis utilized for FDG-PET. Routinely, FDG-PET and CT are
from surrounding bone marrow edema and determination performed in immediate succession, which allows correlation
of the activity state of osteomyelitis cannot be accurately of pathophysiologic and anatomical information. For post-
achieved with MRI, and this remains a diagnostic challenge. traumatic osteomyelitis, a sensitivity between 86% and 94%
Also, recent surgery, the presence of implants, and scar tissue and a specificity between 76% and 100% were reported117
often limit the value of MRI.114 (Table 25.5). However, the evidence for the use of FDG-PET/
Nuclear medicine imaging studies use radiopharmaceuti- CT in osteomyelitis remains low and has to be proven in
cals, which are administered intravenously into the patient. clinical routine.
In contrast to radiologic studies, which use external radiation The role of recently introduced PET-MRI for cardiologic
sources, images are produced by radiation emitted at the and neurologic issues still has to be established in infection
location of the disease within the patient. diagnosis of the musculoskeletal system.
Three-phase nuclear medicine bone scans (TPBSs) using In summary, high-quality radiographs remain a very useful
99m technetium-methylene diphosphonate (99mTc-MDP) and valuable imaging study in the screening and initial
detect areas of increased bone perfusion and bone turnover. treatment planning for chronic osteomyelitis. The value of
Tumors, fracture healing, and infection such as osteomyelitis CT imaging lies in its ability to give a clearer “roadmap” for
lead to increased capillary permeability, which allows capillary the staging of the lesion and for preoperative surgical plan-
leakage of 99mTc-MDP. Moreover, 99mTc-MDP adsorbs onto ning. MRI can be valuable to further delineate the intramedul-
the crystalline hydroxyapatite mineral at the mineralization lary extent of stage 1 lesions and look for possible jump
front of bone representing bone growth by osteoblast activity.
Hence, 99mTc-MDP deposition is a marker not only for local
bone perfusion but also for bone turnover.115 The three phases
are differentiated as the blood-flow phase (0 to 60 seconds Table 25.5 Diagnostic Accuracy Measures
for Peripheral Posttraumatic
post-injection [pi]); blood-pool phase (2 to 5 minutes pi);
Osteomyelitis
and third phase (2 to 4 hours pi), also called static phase,
representing bone metabolism.116 If the first two show an Imaging Modality Sensitivity Specificity
increased tracer uptake with absent or just mild uptake in
Plain radiographs 60% 67%
the delayed phase, soft tissue infection is likely. Increased
tracer uptake in all three phases is compatible with osteo- CT 47% 60%
myelitis. Nevertheless, it has to be taken into account that a
MRI 82%–100% 43%–60%
triple-positive TPBS is still nonspecific for osteomyelitis, and
fractures, tumors, metastasis, and other bone abnormalities TPBS 89%–100% 0%–10%
resemble triple-positive TPBS.111 WBC scintigraphy a
50%–100% 40%–97%
Another nuclear medicine imaging technique for deter-
b
mination of musculoskeletal infection is WBC scintigraphy FDG-PET 83%–100% 51%–100%
or leukocyte scintigraphy. Radiotracer-specific (e.g.,
a
indium-111) labeled leucocytes infiltrate into infected bone Including WBC/CT.
b
Including FDG-PET/CT.
and soft tissue. The drawbacks of this procedure are the
Data from Govaert GA, FF IJ, McNally M, et al. Accuracy of
elaborate labeling process of the WBC and imaging time
diagnostic imaging modalities for peripheral post-traumatic
points 3 to 4 hours and 20 to 24 hours after reinjection, osteomyelitis—a systematic review of the recent literature.
respectively. The dual–time point imaging is necessary because Eur Nucl Med Mol I. 2017;44:1393–1407; supplemented by
increasing WBC accumulation indicates infection, whereas Al-Sheikh W, Sfakianakis G, Mnaymneh W, et al. Subacute
a decrease or a stable uptake in time implies no infection and chronic bone infections: diagnosis using In-111, Ga-67
but inflammation or physiologic bone marrow uptake.116 In and Tc-99m MDP bone scintigraphy, and radiography.
chronic osteomyelitis, the sensitivity and specificity of WBC Radiology. 1985;155:501–506.
scintigraphy are low. In the literature, most studies of WBC

lesions within a long bone. In our experience, nuclear chronic IV antibiotics in the care of such infections has, at
medicine imaging studies have less clinical application from best, limited utility and efficacy in the care of this condition.
a practical viewpoint than do the other mentioned imaging Planning for definitive care in the treatment of chronic
studies. TPBS is not suitable to diagnose osteomyelitis because osteomyelitis must follow an algorithm that is best followed
of its low specificity, but it can be useful in the diagnosis of in every case treated; this helps reduce the risk of missing a
stage 1 cases of chronic osteomyelitis and possible smaller step in the treatment plan. In the first author’s extensive
lesions in cortical bone. However, it is not useful in excluding experience in the treatment of osteomyelitis, this treatment
a chronic osteomyelitic process. WBC scintigraphy is occasion- ladder helps maximize outcomes while minimizing the chances
ally appropriate for the diagnosis of suspected osteomyelitis of skipping a potential necessary step in treatment. It is used
with recent fracture, surgery, and osteosynthesis material in in every case and serves as a useful tool in confirming that
situ, but it is generally not necessary. FDG-PET/CT is a quick a reasonable treatment plan has been devised (Box 25.2).
whole-body imaging procedure with high sensitivity and This may seem a bit burdensome, but once the surgeon
specificity, but it remains unproven in clinical practice, is becomes familiar with the steps, he or she will find that it is
expensive, and is generally unnecessary and therefore remains well worth the mental exercise.
more of a research tool for now. As reviewed in the previous section on diagnostic modalities,
the imaging of the lesion in question can usually be sufficiently
achieved with the use of plain radiographs and often a CT
PLANNING AND TREATMENT OF scan. This is usually all that is necessary to define the extent
CHRONIC OSTEOMYELITIS of the osteomyelitic segment for surgical planning (Fig. 25.7).
However, there are times when the extent of the lesion is
When treating cases of chronic osteomyelitis, it is impera- less clear. In these instances, the use of more advanced
tive that a thorough care plan be developed before surgical imaging modalities such as MRI can be quite helpful. However,
intervention. Most of the time, a diagnosis can and should be one must remember that an MRI study tends to overestimate
established before the surgical intervention. With experience, the extent of the osteomyelitic segment. This is because the
the need for a surgical biopsy to establish diagnosis becomes MRI is really describing the inflammation present in the
the rare exception rather than the rule. This is an important bone, and this often extends beyond the borders of the
point to understand because the classic treatment strategy infected and devitalized bone region. This must therefore
depended on obtaining a tissue specimen to establish an be taken into account when planning the surgery. It has
infecting organism along with speciation of the microbe so been the first author’s experience that in such instances, the
as to tailor systemic antibiotic therapy at the time of definitive surgeon should rely on the CT scan and clinical findings at
excision in overall care. As the experienced orthopaedic the time of surgery to determine definitive surgical excision.
surgeon who treats osteomyelitis has learned, the use of The MRI is especially useful in cases where there is a concern

Box 25.2 Treatment Ladder Algorithm in the Preoperative Planning for the Treatment of
Chronic Osteomyelitis

1. Localize the site and extent of the osteomyelitic lesion. f. Would a free-muscle transfer help with the local wound
a. Is it isolated or multifocal? environment by providing improved local blood flow?
2. Define the Cierny-Mader stage (1 through 4). 5. Is the lesion confined enough such that it can be treated in a
a. If the lesion is a stage 4, is a bony reconstruction possible single surgical intervention, or does treatment require a staged
after complete débridement? approach?
3. Define the Cierny-Mader type of host being treated. a. If treatment requires staged procedures, will a plastic surgeon
a. Type A, Blocal, Bsystemic, C be required?
b. If a B or C host, define precisely the reasons and obstacles b. If plastic surgical assistance is deemed necessary, then
they may pose during the course of treatment. consult before the index procedure to make sure the patient
c. If patient is a Bsystemic or C host who is being considered for is a candidate for appropriate tissue transfer.
treatment rather than amputation, will a prolonged course c. If staged, how will the bone and soft tissue defect be
of systemic antibiotics be necessary? managed in the intervening periods?
d. If a Bsystemic host, can the patient undergo the type of soft d. How will the dead space be managed?
tissue and/or bone reconstruction that might be necessary, 6. Will skeletal stabilization of the bone segment be required?
or should the patient be reclassified as a C host? a. If so, will this best be managed by external or internal
4. Define the condition of the soft tissue envelope. fixation?
a. Is the soft tissue envelope intact? b. If external fixation is preferred, then will this in any way
b. Is there a sinus tract, and does it require excision? interfere with the long-term definitive treatment of the bone
c. If an incision is made, can it then be closed? defect?
d. Will a local soft tissue rearrangement or transfer be c. Does the ensuing bone defect require reconstruction/grafting,
necessary? and if so, is it significant to the point that bone transport
e. Will a free-tissue transfer be necessary to attain a healed might be required?
soft tissue envelope? 7. When and how will bone reconstruction be performed?

Courtesy David W. Lowenberg, MD.

A B
Fig. 25.7 A 62-year-old male with quiescent osteomyelitis. The patient had occasional swelling and increased warmth at his distal leg with
pain. He had no draining wound and no systemic symptoms. (A) Anteroposterior radiograph of right distal tibia. (B) Lateral radiograph of right
distal tibia. Notice the rather clear extent of involvement with relatively sharp radiographic margins. (Reprinted with permission from Lowenberg
DW. A technotheoretical approach to the management of osteomyelitis. Tech Orthop. 2015;30(4):209–214.)

for “jump lesions” within a bone segment because these will host versus a type Blocal host. In reality, the type Blocal is the
be picked up quite nicely with this imaging modality. It will norm rather than the exception in most cases of posttraumatic
also show the extent of bone involvement in C-M stage 1 osteomyelitis. It is important for surgeons to take this into
osteomyelitis provided no hardware is present. consideration in their preoperative planning in the treatment
Once these imaging studies have been obtained and ana- of such cases. The nuances of impaired local perfusion and
lyzed, the surgeon can usually accurately determine the C-M atrophic skin envelopes can have great implications in eventual
stage of the osteomyelitis segment. This is especially important outcome and need careful consideration of how conditions
to determine because it usually has a direct bearing on the can be optimized throughout the global treatment course.
type of treatment initiated. One can appreciate the need for We have learned through experience that when there is doubt
this delineation particularly as to whether the infection is a as to distinguishing between a type A versus type Blocal host,
stage 3 versus a stage 4 lesion because different treatment then one should default to the type Blocal designation and
methods are usually undertaken for bone reconstruction. the implications it brings to potential treatment decisions
The C-M host type must then be taken into consideration because some of our failures were repeatedly caused by doing
for treatment planning. Certainly, in a type C host, one might the opposite.
stop the algorithm pathway at this point if the treatment is As implied throughout this chapter, one must then critically
determined to be too burdensome for the patient to endure, analyze the soft tissue envelope. The first author’s experience
and hence the treatment for this host becomes worse than has been that the leading cause of failure in limb salvage
living with the disease. Although fairly rare, in actual clinical and the treatment of osteomyelitis of the extremities remains
practice, this does occasionally become a reality. This is a lack of attention to the soft tissue envelope. Often when
especially true in a quite elderly patient with a simple chronic evaluating a case of chronic posttraumatic osteomyelitis, one
stage 3 osteomyelitis with an isolated draining sinus tract is faced with either a draining or intermittently draining
who is systemically asymptomatic and has had this condition sinus tract. We have learned that one must look beyond the
for many years. In such a circumstance, it is often the better confines of the sinus tract and look at all the surrounding
decision to let the person simply continue his or her life as tissue. There is often atrophic skin surrounding this area of
is with no further intervention because the treatment would significantly greater extent than just the sinus tract. Often
be potentially worse than the current disease. there is also scarred and fibrotic muscle with limited vascularity
One subtle difference that must be looked at critically and viability around the sinus area. Such a tissue envelope
when staging the host is the distinction between a type A provides for a poor wound-healing environment for any

salvage and reconstruction procedure that is undertaken. When performing preoperative planning and recognizing
This must be evaluated before initial surgical intervention that the soft tissue envelope will require modification to
because in such instances, it is a better alternative to plan include either soft tissue rearrangement (e.g., rotational flap)
for excision of this at the index débridement to allow for an or free-tissue transfer, it is imperative that the surgeon factor
eventual healthy soft tissue bed and creation of what Cierny in the morbidity of both options. We have observed that in
termed “a living wound.” This then requires collaboration an already-impaired limb, a rotational flap (e.g., medial belly
with a skilled microsurgeon to aid in the planned placement of the gastrocnemius) can often cause greater morbidity to
of a free-tissue transfer to allow for a well-vascularized and the later function of the affected limb than if a free-tissue
healed soft tissue envelope. transfer were performed. This is especially true with the
When cutting into an impaired soft tissue envelope as advent of partial muscle harvests for free-tissue transfer.118,119
described previously, one cannot often close this impaired Another less appreciated reason for free-tissue transfer in
tissue, and even if one can get it successfully closed, the the care of chronic osteomyelitis involves the introduction
wound often does not heal. For this reason, it is better to of a healthier wound environment to the affected “zone of
plan on a consult with a skilled microsurgeon in the pre- injury.” This concept was initially popularized in the 1980s.120
operative planning stages so that this can be intelligently However, it lost credibility due to the fact that the thinking
addressed and planned for. The alternative of trying to make was flawed. These patients were treated with free-tissue
an incision away from the impaired soft tissue envelope transfer, but with lack of attention paid to resection of all
(such as the opposite side of the limb) and tunnel over to infected bone (Fig. 25.8). The infected bone was not addressed
resect the osteomyelitic segment is generally a poor deci- with complete and thorough débridement of all infected and
sion because in doing so, you are destroying the healthy devitalized bone. Hence, there was a high rate of recurrence
blood supply and soft tissue envelope around that bone of infection and sinus tracts due to this, with only good
segment. We have found it far better to accept the soft short-term results.
tissue problem for what it is and resect it with the plan of With proper understanding for the need of complete resection
bringing a healthy soft tissue envelope back to it via modern of all infected and devitalized bone, regardless of the seg-
microsurgical free-tissue transfer techniques. This is the mental defect that could resultantly be created, there remains
reason that an orthopaedic surgeon who wishes to pursue a role for the consideration of free-tissue transfer to such a
a career in the treatment of osteomyelitis must be versed in limb to improve the local host conditions. We have found this
the knowledge of methods of and indications for free-tissue to be a valuable adjuvant in the treatment of compromised
transfer. limbs with a chronically compromised soft tissue envelope
Another factor in the soft tissue envelope is the state and further impairing vascularization to the adjacent bone.
location of the sinus tract itself. In areas of better soft tissue Another important consideration in the treatment of
coverage, such as the thigh, it is not uncommon for the sinus chronic osteomyelitis involves the type of free-tissue transfer
tract to not be at the same level on the limb as the accompany- chosen to re-create a deficient or compromised soft tissue
ing bony site of pathology. This is because the egress follows envelope. There has been a great resurgence in popularity
the path of least resistance, and gravity also plays a role in of free fasciocutaneous tissue transfers, such as the antero-
this track. It is therefore common for such a tract to be distal lateral thigh flap (ALT), by microsurgeons in the care of
and sometimes slightly posterior to its source in bone. Fascial such limbs. Although they do provide a cosmetically pleasing
planes do stop such a tract from tracking past them as a rule, coverage, work done by Mathis et al. between 1982 and 1990
so if the outer cortical penetration of the tract from the showed the relative superiority of the muscle flap.121–124 These
bone is anterior to the intermuscular septum of the lateral authors showed in a dog model that there was a significantly
thigh, it won’t track posterior to this. However, if the site of increased blood flow in the wound bed under a musculocu-
penetration is posterior to the intermuscular septum, we taneous flap compared with a fasciocutaneous flap. There
have seen midfemoral lesions present with a sinus tract near was also a significantly greater decline in bacterial cell counts
the popliteal fossa. It is important that the surgeon realize over time and a greater degree of inhibition and elimination
this and look throughout a limb segment when a sinus tract of bacterial growth after inoculation under the musculocutane-
is the presenting sign. ous flaps compared with fasciocutaneous flaps.
In cases of a sinus tract at a distant site from the affected Also, it was found that with bacterial reinjection into the
bone, we have found it often unnecessary to resect the tract dermal layer of a fasciocutaneous flap, there was greater skin
and instead leave it and use it as a “barometer,” if you will, necrosis than with the same inoculum into the dermis of
to monitor whether the resection and eradication of the musculocutaneous flaps.121 It was also noted that skin death
infection were successful. The exception to this is in cases with bacterial injection into the wound bed occurred 86%
where there is necrotic soft tissue accumulating along the of the time in fasciocutaneous flaps compared with no cases
course of the tract. In such cases it is probably better to at least in musculocutaneous flaps in these dogs. It was also noted
clean this out. Regardless of whether the tract is excised, the that there was no difference in susceptibility to infection
goal of treatment remains the creation of a “living wound.” between dermal inoculation of bacteria in musculocutaneous
One must get used to the concept that a wound does not flaps compared with native host tissue. Last, this work found
just imply the soft tissue but also implies the health of the that the phagocytic activity of leukocytes was 1.5 times greater
bone. In other words, in treating osteomyelitis, a “wound” and the intracellular bacterial killing ratio was 3 times greater
implies all components of tissue, including bone, in the area in the wound beds under a musculocutaneous flap as com-
of infection. This is a bit contrary to what we as orthopae- pared with fasciocutaneous flaps in this dog model. All these
dic surgeons tend to think, but it remains an important data point to reasonably good science backing the superior
paradigm shift. efficacy of muscle compared with fasciocutaneous and

A B
Fig. 25.8 A 54-year-old male who developed chronic proximal tibial osteomyelitis secondary to a fracture 30 years prior. He underwent limited
débridement of infected bone and free latissimus transfer over the bone segment 25 years prior. Five years after this, he began to again develop
intermittent drainage under the flap. This then worsened 2 years prior with a draining sinus tract, and he presented for evaluation. (A) Coronal
T2 fat-suppression magnetic resonance imaging (MRI) of residual osteomyelitic lesion with necrotic focus and surrounding bone edema. (B)
Sagittal T2 MRI showing lesion and sinus tract exiting at the inferior border of the free latissimus transfer. (Courtesy David W. Lowenberg, MD.)

subcutaneous tissue in providing an improved local wound We have found that this is best achieved via the use of an
environment for eradicating residual planktonic cells that open antibiotic bead pouch (Fig. 25.9).
might exist in the wound bed. This technique remains the preferred method of dead-space
In the planning and treatment of the bone excision, one management in such instances and has been used by the first
must then determine how much of a bone resection is author for over 20 years, with reproducible and excellent
required. If it is deemed that the lesion is quite small, then results. It provides the best of all worlds for a wound in that it
sometimes a very limited excision of a non–full-thickness lets the wound evolve in a healthy environment for the local
portion of the cortex becomes all that is necessary. If one is cell population, with it being bathed in serum and hematoma.
also planning on closing an intact soft tissue envelope at the This would normally be a detrimental environment because
same time as bony excision, then it is also often prudent to this represents an ideal medium for prokaryotic growth.
administer a local depot antibiotic at the site as an adjunct However, this medium is now enriched with a high dose of
and also to provide any “dead-space management.” The first local antibiotic delivery, thereby killing any residual planktonic
author often accomplishes this with a custom-constructed cells and also acting against the disrupted environment of
gel foam and antibiotic powder–laden complex. This deals the sessile-phase bacteria. This is due to the supra-physiologic
with dead-space management and adjuvant high-dose local concentrations that can be achieved with this delivery and
antibiotic delivery for any free planktonic phase cells released. elution method. This provides a local environment in the
It is imperative at this stage of bone resection planning host tissue far healthier than that of a nonphysiologic high-
to once again go back to the soft tissue envelope. If a soft negative-pressure environment. In fact, it is our experience
tissue defect will be created at the time of the bone resection, that negative-pressure wound therapy is directly harmful to
then the surgeon must plan how the combined bone and cortical bone, and we have seen numerous cases of cortical
soft tissue envelope is initially managed because more often bone necrosis as a direct result of negative-pressure wound
than not, the definitive soft tissue coverage is not performed therapy. Our microsurgeons as well now appreciate this and
at this index débridement surgery. prefer sterilizing a wound with an open antibiotic bead pouch
In such instances, it is the first author’s usual practice to over the use of a negative-pressure wound therapy system.
create temporary coverage of the affected wound while at Regardless of which method is employed, dead-space manage-
the same time providing high-dose local antibiotic delivery. ment remains an integral part of the overall treatment method

A B C
Fig. 25.9 A 28-year-old male status post–pedestrian versus motor vehicle accident when trying to run across a freeway. The patient suffered
multiple injuries, including this type 3B open left tibia and fibula fracture with segment bone defects. He underwent serial débridement of the
necrotic bone and soft tissue staged with an open antibiotic bead pouch before free-muscle transfer. (A) Débrided wound bed before placement
of bead pouch. (B) Custom bead pouch placed in wound bed. (C) Bead pouch after coverage with circumferential sticky cellophane iodine-
impregnated dressing. (Courtesy David W. Lowenberg, MD.)

It is no accident that reconstruction of the bone is the last

Table 25.6 Stepwise Algorithm for the
step in this treatment ladder. This is intentional because it
Treatment of Chronic Osteomyelitis
will invariably fail unless the three prior steps are successfully
Temporal Order Reconstruction Step Performed completed.
After the successful débridement of the involved bone,
1 Excise all devitalized/infected bone and
the surgeon must then decide whether the bony defect created
soft tissue.
requires skeletal stabilization. Clearly, small defects often do
2 Manage the dead space. not require any skeletal stabilization. However, large C-M
3 Obtain a healed soft tissue envelope.
stage 3 and essentially most if not all stage 4 cases do require
some form of stabilization of the limb. This is not the stage
4 Reconstruct the bone defect. in preoperative planning when it is best that the surgeon
plan on a definitive plan for the long-range reconstruction
Reprinted with permission from David W. Lowenberg, MD. of the bone defect created. The surgeon must first decide
whether the best option is definitive internal fixation versus
definitive external fixation versus initial short-term external
bridging fixation followed by internal fixation. All these
options are viable and reasonable choices that should be
in the care of chronic osteomyelitis. It is a key component individually tailored to the problem at hand and the situation
in the treatment algorithm and must not be overlooked. in the host. This would include the psychological and emo-
This algorithm is summarized in Table 25.6. tional state of the host as well as the physical abilities of the
When treating cases of chronic osteomyelitis, it is important host to deal with these different treatment methods.
that the surgeon follows this orderly treatment ladder. One When initial fixation utilizing internal fixation is chosen,
can skip a step in the treatment ladder (e.g., not directly the first author prefers combining this with an antibiotic
addressing the soft tissue envelope if a well vascularized and delivery system. Antibiotic-coated plates and nails can serve in
healed envelope already exists), but it is not reasonable to achieving this. The first author has used high-dose antibiotic-
ignore any of the steps or their order in treating such cases. impregnated cement plates in the initial management of

chronic osteomyelitis for the past 20 years in over 150 The beauty of the C-M staging system is that it helps in
cases, with great success. It remains one of the preferred deciding the best treatment options for treating the patient.
methods for provisional treatment in many such cases (see We now outline our preferred treatment methods for recon-
Fig. 25.4). The same can be done with the construction of struction utilizing this staging system.
antibiotic-impregnated cement nails. We prefer using the plate When a stage 1 lesion is diagnosed, it should be addressed
technique in most cases because the majority of C-M lesions from the intramedullary aspect of the bone if possible so as
treated are stage 3, so there is a resultant surgical insult to to minimize periosteal disruption. This remains the perfect
the periosteum, and we prefer to limit injury to both the and primary indication for the use of custom antibiotic/
periosteal and endosteal sides of diaphyseal bone as much cement intramedullary nails. The lesion is first delineated
as possible in treating this condition. Therefore for stage 3 by appropriate imaging studies. It is then gently reamed and
lesions, antibiotic plating and bridging circular fixation have irrigated (assuming it is a long bone) to eradicate the infec-
become the preferred treatment modalities both in the acute tion. Care should be taken to ream this only to the extent
débridement phase and the bone reconstruction phase of required to remove the infection. The dead space is then
treatment. The antibiotic plate can then be converted to a best treated with the custom high-dose antibiotic/cement
standard plate at the time of bone grafting to reconstruct nail. This implant is generally left in place for 6 to 8 weeks.
the diaphyseal defect that has been created. If the patient has any significant degree of immunosuppression
If the osteomyelitic segment is a C-M stage 4, then we tend (i.e., a C-M type Bsystemic host) then sometimes a second look
to treat this with a circular fixator or locked antibiotic nail with repeat débridement and replacement of a new antibiotic/
and later bone grafting for defects 2 cm or under. For defects cement nail is warranted. This implant is then removed again
over 2 cm, we continue to prefer bone transport because it 6 to 8 weeks later (Fig. 25.10).
has a success rate of over 95% in our hands and, in most Cierny-Mader stage 2 lesions are actually the rarest form
hosts, is extremely reproducible. of osteomyelitis encountered in clinical practice. This is

A
Fig. 25.10 A 58-year-old female who 8 years prior was treated for a closed right distal one-third proximal two-thirds junction tibia fracture.
She had continual pain since soon after the surgery and could only ambulate short distances due to the pain. She was told nothing was wrong.
She then underwent a Tc99 bone scan, which showed increased uptake along the majority of the diaphysis. For this, she was treated with
dynamization of the fracture with removal of the distal interlocking screws even though the fracture had been healed for many years. The pain
persisted. She was then referred for care. The patient had normal inflammatory markers over this 8-year period. She was diagnosed with
Cierny-Mader type 1 osteomyelitis and underwent removal of the nail, irrigation and reaming of the canal, and placement of a high-dose
antibiotic/cement custom nail. Intraoperative cultures grew Propionibacterium acnes. No systemic antibiotics other than perioperative antibiotics
and a 5-day course of oral cephalexin were prescribed. Six weeks later, the antibiotic nail was removed. Her deep bone pain resolved within
5 days of initial nail removal and never returned with 3-year follow-up. (A) Anteroposterior (AP) radiograph of right tibia soon after index rodding.
(B) Lateral radiograph of right tibia soon after index rodding. Continued

C D

E F
Fig. 25.10, cont’d (C) AP radiograph 3 years after index rodding; notice slight mid-diaphyseal periosteal reaction. (D) Lateral radiograph 3
years after index rodding. (E) AP radiograph 8 years after index rodding, with increased midshaft periosteal reaction and cortical hypertrophy.
(F) Lateral radiograph 8 years after index rodding.

I J

Fig. 25.10, cont’d (G) Bone scan of right tibia showing increased uptake of tracer at the midshaft diaphyseal region. (H) Axial computed
tomography (CT) cut of midshaft of tibia showing periosteal new bone around intramedullary osteomyelitis. In essence, an involucrum around
the endosteal osteomyelitis had formed. (I) AP radiograph after intramedullary débridement and placement of custom antibiotic/cement nail.
(J) Lateral radiograph after placement of antibiotic/cement nail. Continued

K L
Fig. 25.10, cont’d (K) AP radiograph 7 months after antibiotic/cement nail removal; patient remained completely asymptomatic. (L) Lateral
radiograph 7 months after antibiotic/cement nail removal. (Courtesy David W. Lowenberg, MD.)

because many stage 2 lesions are not what they appear on necessary, then this usually occurs within a week after the
initial clinical presentation. It is the first author’s rule to débridement. If a free-tissue transfer is necessary, then bone
assume that all perceived C-M stage 2 lesions are actually reconstruction is usually delayed for 3 to 4 months to allow
stage 3 lesions until proven otherwise. In a true stage 2 lesion, the flap to fully heal before this is elevated for further bone
burring or cutting of the diaphyseal necrotic segment until reconstruction/grafting. If no soft tissue reconstruction is
good bleeding is encountered usually suffices for treatment. necessary, then the skin is allowed to further heal with the
The dead space is often best treated with either a resorbable bead pouch in place, usually for 6 to 8 weeks. Then bone
or nonresorbable material laden with antibiotic (Fig. 25.11). reconstruction is initiated (see Fig. 25.4). This approach
If there is a compromised soft tissue envelope, then leads to extremely predictable and reproducible results in
appropriate management of this must be undertaken and our hands, with a cure rate of at least 95%.
reconstruction of this completed before reconstruction of A word of caution in the treatment of C-M stage 3 lesions
the bone, as outlined in the reconstruction ladder (see Table involves the use of antibiotic/cement nails. On many occa-
25.6). If this is staged in any way, then an open antibiotic sions, the first author has received cases of failed treatment
bead pouch remains our preferred intermediary treatment of C-M stages 3 and 4 chronic osteomyelitis treated with
method. One must remember that if the intramedullary canal antibiotic/cement nails in which the treating surgeon felt
is entered while still trying to find bleeding bone, then by that this device would cure such infections. In no way does
definition, this is a C-M stage 3 lesion and should be treated this or any other local antibiotic delivery system provide a
as such. definitive cure for this problem. The cure is in the form of
In the first author’s experience, C-M stage 3 lesions are proper and thorough débridement along with appropriate
the most common stage of chronic osteomyelitis encountered dead-space management. When misused for what they are
in clinical practice. The reconstruction ladder in Table 25.6 intended to do, these devices will fail consistently in such
represents the cornerstone for treatment of these stage 3 applications.
and stage 4 lesions. Débridement of all necrotic bone and Treatment of C-M stage 4 lesions requires circumferential
soft tissue followed by dead-space management (in our hands, en bloc excision of the infected bone segment. An infected
this is usually with the use of an antibiotic bead pouch, either nonunion represents such a scenario and is a prototype
closed or open) remains the cornerstone of initial treatment. example of such a lesion. The key to the treatment of C-M
We prefer saucerization of the bone, usually in the form of stage 4 lesions is the recognition that the lesion is in fact a stage
an ellipse with no acute edges or corners. The saucerized 4 lesion. The differentiation between a stage 3 and stage 4
portion must be large enough to allow for excision of all lesion is therefore critical. The inverse is also of extreme
devitalized/infected bone within the medullary canal as well importance to differentiate; the first author has seen many
and must allow for the placement of antibiotic beads in the cases of “overkill” where a stage 3 lesion is treated as if it
bone defect. If the defect created is substantial enough that were a stage 4 lesion. This causes unnecessary treatment
it could compromise skeletal stability, then skeletal stabilization time and trauma to the patient. Needless to say, a true stage
is done either with external fixation or an antibiotic/cement- 4 lesion requires circumferential resection. We again prefer
impregnated bridge plate. If soft tissue reconstruction is autogenous grafting to later reconstruct the bone defect if

D
Fig. 25.11 A 17-year-old female sustained a deep abrasion to her left pretibial region at age 13. This healed over uneventfully. At age 16 she
began developing pain about the tibial shaft at the site of the old abrasion. Radiographs revealed a lytic lesion with sclerotic borders at the
anterior cortex. This was curetted out by another surgeon after being diagnosed as a Brodie abscess. Intraoperative cultures were negative.
After 3 months, this failed to further heal, and the patient continued to have pain and could not return to competitive volleyball. For this reason,
she was referred for care. This was watched for another 9 months, with only slight improvement in her pain when attempting to play volleyball.
Radiographs failed to ever show complete healing of the anterior cortex, and with time, the anterior lucency worsened. The family then agreed
to reintervention. She was taken back to the operating room (OR) for redébridement with a diagnosis of chronic osteomyelitis with a Cierny-Mader
stage 2 lesion. The defect was filled for dead-space management with a high-dose antibiotic-laden cement mixture. Cultures grew methicillin-
sensitive S. aureus. Only perioperative antibiotics were given. At 6 weeks postoperative, the cement was removed and bone graft applied. The
patient healed uneventfully, with complete resolution of her pain. (A) Anteroposterior (AP) radiograph 4 months after excisional biopsy of lytic
lesion of right pretibial lesion diagnosed as a Brodie abscess. (B) Lateral radiograph of lesion. (C) AP radiograph 7 months after excisional
biopsy, with incomplete healing of lesion. (D) Lateral radiograph 7 months postexcision. Continued

G
Fig. 25.11, cont’d (E) Lateral radiograph 9 months after excisional biopsy. (F) Lateral radiograph 12 months after excisional biopsy, with
persistent lack of healing and further lucency indicative of ongoing osteomyelitis, with sclerotic edges. (G) AP radiograph after repeat débridement
and filling of anterior defect with high-dose antibiotic cement. (H) Lateral radiograph after redébridement.

it is under 2 to 3 cm and bone transport for defects larger induced membrane technique has shown success rates in
than this (Fig. 25.12). Other techniques have been described, the mid- to low-80% range in attaining an often implant-
such as the induced membrane technique, and acute shorten- dependent union. These numbers do not yet match the
ing of the resultant defect with later lengthening of the success rate of bone transport. Acute shortening with distant
affected limb segment. The authors continue to favor bone segment lengthening has been described for many years,
transport as the method of choice in larger defects. The first but the authors find it less well tolerated by patients with
author has regularly practiced this technique for larger defects greater alteration in muscle mechanics and therefore prefer
for the past 28 years, with a success rate well over 95%. The bone transport if it can be done.125

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uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
I J
Fig. 25.11, cont’d (I) AP radiograph 4 months after cement removal and bone grafting of defect. Complete resolution of all symptoms.
(J) Lateral radiograph. (Courtesy David W. Lowenberg, MD.)

A B C
Fig. 25.12 A 14-year-old female was diagnosed with osteogenic sarcoma of her right proximal tibia for which she underwent chemotherapy,
radiation, and resection with placement of an intercalary allograft and plating along with skin grafting around the proximal tibia. At 1 year she
was free of disease but developed a nonunion with varus deformity, which underwent replating. Two weeks after this surgery, deep infection
occurred. This was initially treated with intravenous then oral antibiotics for suppression, but this treatment failed. She was then scheduled at
age 15 for an above-knee amputation (AKA). The family refused, and she was transferred for care. She underwent en bloc resection of the
allograft segment (which was a Cierny-Mader [C-M] stage 4 osteomyelitis) with resection of any necrotic host bone and stabilization with a
ring fixator. She then underwent distal-to-proximal bone transport for the 15-cm tibial defect. The docking site did not want to heal due to a
poor soft tissue envelope, so free-muscle transfer to improve the wound bed was performed with repeat grafting and repeat short-segment
bone transport into the docking site to compress the docking site and maintain limb length. She went on to heal with equal limb lengths and
normal limb alignment. She is 21 years out from completion of treatment, married with children, and working as a dentist. (A) Anteroposterior
(AP) radiograph of right tibia after resection, allograft placement, and plating. (B) Lateral radiograph. (C) AP radiograph 1 year postoperative,
with varus and nonunion at proximal interface site. Continued
Descargado para Diego Alvarado Gómez (diego.alvarado.g@usach.cl) en University of Chile de ClinicalKey.es por Elsevier en mayo 08, 2023. Para
uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
736 Section ONE — General Principles

D E F

G H I
Fig. 25.12, cont’d (D) Lateral radiograph. (E) AP radiograph after en bloc resection of C-M stage 4 chronic osteomyelitis with 15-cm tibial
defect. (F) Lateral radiograph. (G) AP radiograph early in bone transport. (H) AP radiograph later in bone transport. (I) AP radiograph after frame
removal with failure of docking site union after grafts due to poor soft tissue envelope.

J K L

M N
Fig. 25.12, cont’d (J) Lateral radiograph. (K) AP radiograph after completion of treatment with free-muscle transfer to docking site with repeat
bone grafting and frame stabilization; 4 months after removal of circular fixator stabilization. (L) Lateral radiograph. (M) AP radiograph 16 years
after completion of treatment. (N) Lateral radiograph. (Courtesy David W. Lowenberg, MD.)

Vascularized bone grafts such as free fibula transfer have not represent a cure of the condition in any way. When
also been well described. We reserve these mostly for the properly done, this does not mean continual administration
use of segmental defects to the non–weight-bearing long bones of an antibiotic systemically. Ideally, it involves intermittent
of the upper extremity due to the high rate of late fracture administration of the most non–broad-spectrum antibiotic that
of the fibula with ambulation and increased activity due to can be successfully used and for the shortest amount of time.
the long time required for adequate hypertrophy to occur.126 The idea is for the systemic antibiotic to attack only planktonic
In light of more recent data, it is also important for the cells released from the biofilm colony. This is to control and
treating surgeon to realize that in reality, more nonunions reduce any systemic effects and, in effect, signal the biofilm
than we have previously appreciated are probably infected.78 colony to stop releasing planktonic cells. The colonies often
The surgeon experienced in the treatment of nonunions respond in this fashion and simply go back to existing without
and infections is acutely aware of this and will be suspicious planktonic shedding and in their sessile phase within the
of this fact when encountering a nonunion. It is our current biofilm matrix.
practice when treating any nonunion to have a high index The reason it is important to limit the type and amount
of suspicion that it could be infected and make sure to take of antibiotic consumed by the patient lies in the “collateral
this into consideration in its treatment. damage.” This damage involves the promotion of further
development of antibiotic resistance. This has been confirmed
by the US Food and Drug Administration (FDA) as a major
AMPUTATION FOR TREATMENT
health problem.128–130 A recent set of experiments by Baym
Despite our best efforts, some limbs are just not amenable et al. has shown how rapidly microbial resistance can occur
to limb salvage, due to either the extent of the infection, with increasing doses of an antibiotic.131 This has now been
distal neuropathy, nonreconstructable soft tissue envelope, recognized as a global health problem.
the psychological state of the patient, or the overall general The other reason that it is important to limit the use of
health of the patient. In these instances, it is reasonable to a chronic antibiotic in an individual lies in the health and
then consider limb amputation. Most would agree that this welfare of the individual being treated. Chronic systemic
is especially the reasonable option in the elderly especially antibiotic consumption, regardless of the route of administra-
if the osteomyelitis is secondary to Charcot changes and tion, alters the individual’s natural microbial flora. This is
neuropathy. In these instances, a well-done below-knee, especially true of the individual’s gut flora. The gut flora has
through-knee, or above-knee amputation is often the treat- been implicated in maintaining the proper health of an
ment of choice. In our experience, with newer methods of individual. Alterations in the natural gut flora have now been
limb salvage, most cases of osteomyelitis in the younger patient implicated in a host of disease states and have also been
population in which a good host exists are quite successfully implicated in altering the ability of the host to absorb and
treated with preservation of the limb. Amputation rates of metabolize nutrients.132–134 This can hence lead to further
the lower extremity, though, tend to remain at about 10% impairment in the host’s ability to fight infection and further
of lower extremity chronic osteomyelitis cases.127 Obviously, sicken rather than help the host. It is imperative that the
a lower-level amputation (below knee) allows for better surgeon understand this and be wary of this when prescribing
function than more proximally (above knee). any chronic regimen of antibiotics to a patient.
When amputation is decided on, the surgeon must take
care in proper operative planning for the “fine-tuning” of
TIPS AND PEARLS IN TREATMENT
the amputation level on the particular limb segment. The
key to a successful amputation with the types of prosthetics In concluding this section on the treatment of chronic
currently in use remains a stable and adequate soft tissue osteomyelitis, certain key points deserve stressing. Chronic
envelope. Sometimes, consultation with a plastic surgeon osteomyelitis is a surgical disease. We have found the role
versed in soft tissue rearrangement procedures is quite valu- of continuous systemic antibiotic administration to be of
able. We feel that preoperative consultation with the pros- little if any value, and recent data show that this could also
thetists who will be working with the patient after amputation likely cause harm to the host’s ability to effectively fight
is also critical. Therefore this requires a well-planned team infection. The data for this conclusion were referred to earlier.
approach. Therefore the hallmarks of treatment as outlined in Table
In regard to the upper extremity, one must try to avoid 25.6 must be followed, and the administration of long-term
amputation if possible. This is true in the elderly as well, in antibiotics is intentionally left off the list in this table.
that patients generally do poorly with upper extremity The importance of proper management of the soft tissue
amputation. In the elderly, loss of an upper extremity does envelope and its contribution to optimizing outcome cannot
not just impair upper extremity function but mobilization be overstated. We have discussed earlier that a healthier soft
as well because these patients often have accompanying tissue envelope alone cannot cure osteomyelitis.120 However,
comorbidities and impaired ambulation ability. They therefore without a stable and healthy soft tissue envelope, the bone
often require an ambulatory aid, and with a deficient upper reconstruction can fail. This is why it is our approach that
extremity, this becomes a serious problem. in any case of chronic osteomyelitis with an impaired soft
tissue envelope, a team approach with the incorporation of
experienced microsurgeons is imperative to proper care.
ANTIBIOTIC SUPPRESSION THERAPY
Another topic that has been left off the treatment arsenal
In some patients who are true C-M type C hosts, the treatment is hyperbaric oxygen. It has been our observation that
is more perilous than the disease. In such cases, the discussion hyperbaric oxygen added little to the care of patients being
of suppressive therapy often ensues. Suppressive therapy does treated for chronic osteomyelitis, despite reports to the

contrary.135,136 However, in 2012 Shandley et al. published sessile phase of prokaryotic growth, we have greatly limited
basic scientific work confirming our observations. They showed their use in the treatment of chronic osteomyelitis. In patients
in a mouse model of osteomyelitis that hyperbaric oxygen who are C-M type A or C-M type Blocal hosts, IV antibiotics
added no efficacy in the curing of the infection, and in the are limited to the perioperative resection period and are
case of MRSA, it actually added to the pathogenicity of the generally given for 2 to 3 days. Occasionally patients go
Staphylococcus.137 Although hyperbaric oxygen might have home with a 5- to 7-day oral antibiotic regimen. With this
some benefits in diabetic wound healing and certain other treatment algorithm, which the first author has used for
discrete applications, because of its burden to the patient, nearly 25 years, a long-term cure/eradication of infection
cost, and lack of efficacy, it is not used in the treatment of without recurrence has been achieved in roughly 95%
chronic osteomyelitis. of patients treated. For this reason, it is the first author’s
Last, much has been said over the years of the risk of practice that only 5% of patients treated for chronic
leaving a chronic sinus tract and the resultant transformation osteomyelitis actually leave the hospital with an IV line for
to a squamous cell carcinoma. This has been well reviewed antibiotic administration. During this time period, there were
recently by Panteli et al.138 In all the authors’ combined episodes where infectious disease physicians instituted long-
experience, this has only been encountered on a total of term antibiotic usage despite recommendations not to do so.
three occasions, and in all three cases, this was not the cause There was never a perceived improvement in outcome with
of the ultimate demise of the patient. Although this entity this practice.
is well recognized, its clinical implications are probably less We are not alone in this thinking; it mimics the long-term
of a concern than previously reported. practice of the late George Cierny. Similar results have also
been reported in the past by other authors.142 All data on
the long-term use of systemic antibiotics in the treatment of
ROLE OF SYSTEMIC ANTIBIOTICS IN THE chronic osteomyelitis are anecdotal at best, with no science
TREATMENT OF CHRONIC OSTEOMYELITIS behind the conclusions.143 The reasoning of such a perspective
is that without them, there is a high rate of recurrence. By
In concluding this chapter, one cannot exclude an issue that definition, that is stating that the nidus of dead bone, biofilm,
has faced the orthopaedic surgeon treating chronic osteo- and infection was never properly addressed or excised in
myelitis for many years. That issue involves the use and the first place and hence does not represent a reasonable
duration of IV antibiotics. There is no question that a skilled argument for its practice. Data exist as well that this longer-
infectious disease physician is an integral part of the treatment term usage of systemic antibiotics alters the gut microbiome
team in the care of such patients. The first author has two and thereby alters the metabolism and absorption of
infectious disease physicians whom he has helped train in food and nutrients. This adversely alters the health of the
the subspecialty of musculoskeletal infectious disease, and host and impairs the host’s ability to fight infection.
these are the only two infectious disease physicians consulted We therefore advocate proper antibiotic stewardship with
in the care of patients with chronic osteomyelitis. Our infec- limited use of any long-term systemic antibiotics in the treat-
tious disease physicians with this added specialty training ment of all C-M type A and type Blocal hosts. Treatment of
understand the futility and danger of chronic systemic C-M type Bsystemic and type C hosts remains debatable.
antibiotic administration and avoid this practice in the treat- By following the constellation of diagnostic and treatment
ment of chronic osteomyelitis. It is imperative that the tools outlined in this chapter, the experienced surgeon should
infectious disease physician and the orthopaedic surgeon be able to achieve a very high cure rate in this once-untreatable
are well versed and up to date in the treatment of this entity condition.
and understand the potential harm of chronic systemic
antibiotic administration. You cannot make up for an incom-
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