Chapter 26: Orthopedic Infections and Osteomyelitis

Bruce H. Ziran, Wade R. Smith, Nalini Rao

Chapter Outline

Introduction

The first descriptions of infections date back to the early Sumerian carvings, when the tenets of treatment were irrigation, immobilization, and bandaging.83 In these early times, the practice of infection and wound care was essentially an art and there was very little science applied to it. Treatment included the use of honey, wine, and donkey feces, and there were a number of philosophies regarding the value of purulence. Dominant personalities had a significant influence over medical practice and the value of purulence persisted because of the writings of Galen of Pergamum (120 to 201 ad). It was not until the latter third of the second millennium that the concept of the value of purulence would be challenged.83 
In the past three centuries, the treatment of infection has involved the use of local ointments or salves and the maintenance of an open wound that permitted purulence to exit the body. Some important terms were adopted into medical parlance. A sequestrum was defined as “a fragment of dead bone separated from the body.” The word sequestrum is derived from the Latin words sequester meaning “depositary” and sequestrate meaning “to give up for safe keeping.” The word sequestrum is used to describe a detached piece of bone lying within a cavity formed by necrosis. The term involucrum derives from the Latin word involucrum meaning “enveloping sheath or envelope.” This term describes the effects of the body’s inflammatory response when trying to envelope and isolate the sequestrum from the host. The natural history of osteomyelitis was seen as the process of isolation of the infective material followed by a slow attempted resorption of the material by the immune system. However, the term osteomyelitis was not coined until the mid-1800s, when it was adopted by Nelaton.99 
In his book The Story of Orthopaedics, Mercer Rang99 describes the three pivotal discoveries that allowed orthopedic surgery to be successful: anesthesia, antisepsis, and radiography. The first two were important in all surgical specialties. Anesthesia made surgery tolerable, but there was still considerable morbidity secondary to infection. It was not until the mid-1800s that progress with antisepsis permitted infection control and more effective surgical intervention. As a result of this, infection issues became an integral part of medicine and were studied in a more formal basis. However, descriptions of the first sequestrectomies of the tibia had been illustrated as early as 1593 by Scultetus.99 
Before anesthesia, most operative procedures were performed using forced immobility and inebriation. Operating rooms were created because procedures undertaken in the wards horrified patients who witnessed them and the screams of agony did nothing to encourage other patients to seek surgical treatment. Thus, the patients were isolated from the rest of the ward. In the same era, many modern drugs were developed, including morphine, heroin, nitrous oxide, and ether. Ether was in fact serendipitously identified as an anesthetic agent during one of the drug parties that were common at this time. However, it was first used for anesthesia in Massachusetts General Hospital in 1846 by William TG. Morton, and its use quickly caught on around the world. This increased the incentive to undertake surgical procedures. The ensuing increase in the number of surgical procedures, together with the lack of antisepsis, meant that the morbidity and mortality of surgery also increased.99 Pasteur and Lister are most commonly credited as being the forerunners of antisepsis, but the most notable achievement in demonstrating the efficacy of bacterial transmission is the work of Semmelweis, who, in 1848, demonstrated that hand washing between obstetric deliveries reduced maternal mortality from 18% to about 1%. Lister read Pasteur’s work on fermentation and likened tissue putrefaction to the same process. He subsequently developed carbolic acid, which reduced mortality from amputation from 43% in an untreated cohort of patients to 15% in a treated cohort. Despite this significant discovery, his findings were resisted for decades. Even when his concepts were adopted, the remaining pieces of the puzzle required for successful aseptic surgery did not come together for another 100 years. 
The initial use of antibiotics was just as serendipitous as the use of anesthesia and antisepsis. Some antibacterial treatments were introduced, but it was not until the discovery of penicillin (PCN) by Alexander Fleming in 1928 that the proven usefulness of antibiotics became understood. Even Fleming did not vigorously pursue his discovery. However, when Florey and Chain read Fleming’s initial report, they pursued and found the true impact of PCN, which was effective against streptococci. Since then, many antibiotics have been developed,101 but the number of resistant bacteria has also increased. Hand washing, gloves, hats, enclosed rooms, aseptic techniques, and early antibiotics all slightly decreased the incidence of surgical infection. However, the operating theaters in the early 1900s still admitted observers who coughed, did not use masks, and wore street clothes. It was not until the mid-20th century that surgeons began to integrate all the controllable aspects of patient exposure to infectious agents by attempting to standardize the contributive effects of the environment, patient, surgeon, wound, antisepsis, antibiotics, and surgical techniques. It is likely, though, that many of the answers to the problem of infection remain undiscovered, and it seems likely that at the moment we do not fully understand the complex symbiosis between bacteria and humans. 
This chapter will concentrate on the description, etiology, diagnosis, and management of orthopedic infections, but will have a specific focus on posttraumatic conditions. There will be an additional focus on institutional infection control and on infections in the geriatric orthopedic patient, this being a section of the population that is growing rapidly. 
To treat orthopedic infection, one must first understand the basics of the interdependence of humans and bacteria. Bacteria are a necessary part of our existence and normal flora live in abundance on our bodies. It is worth considering that an individual’s skin can contain up to 180 different types of bacteria at any given time.46 There are up to 10 colony-forming units (CFUs) of bacteria in the mouth and perineum. Nearly 95% of bacteria found in the hands exist under the fingernails. The average human is composed of 100 trillion cells, but it is thought that we harbor over a 1,000 trillion bacteria in or on our bodies. Our blood is constantly infiltrated with bacteria from breaks in the skin, translocation across mucous membranes, and other roots. However, nearly all of these bacteria are quickly and efficiently eradicated by our host defense mechanisms. It is the disruption of our own homeostasis that provides an opportunity for either external contamination or opportunistic host bacteria to become pathogenic and cause infection. Although colonization necessarily precedes infection, the presence of bacteria by itself does not constitute infection. This is highlighted by the findings of one study of hardware removal in which 50% of cultures were positive in patients with no signs of symptoms or infection.81 Thus, there is an important distinction between colonization and infection. Understanding the factors that have changed the local or systemic environment with resultant bacterial infection is the key to effective prophylaxis, treatment, and improved outcomes in orthopedic surgery. 
Historically, the treatment of orthopedic infection was either ablative, when an amputation was performed, or temporizing with the treatment of a chronic wound or sinus. There was little chance of limb salvage as we know it today, and infections that were not adequately treated would occasionally become systemic and fatal. 
Certainly, the high mortality of open gunshot wounds to the femur in the American Civil War and World War I was largely caused by sepsis. In every war, the science of surgery and medicine advances, and this is particularly true for trauma surgery and extremity injuries, which still account for approximately 65% of all war-related injuries.84 Thus, many advances in infection treatment and extremity injuries have ironically come about as a result of war. The recent Middle East conflicts have been associated with a lower mortality than earlier wars with most orthopedic casualties being caused by blast injuries. This has mainly influenced infection control and prosthetics. Many soldiers presented with severe contamination from battlefield injuries that precluded acute definitive fixation. This prompted researchers to investigate the best methods of tissue reconstruction in the presence of significant contamination. The inevitable amputations that were required caused a renaissance in the prosthetics industry. 

Classification

Historically, osteomyelitis was classified as either acute or chronic depending on the duration of symptoms. Kelly61 documented a classification system based on the etiology of the osteomyelitis. There were four types with type I being hematogenous osteomyelitis. Type II was osteomyelitis associated with fracture union, whereas type III was osteomyelitis without fracture union and type IV was postoperative or posttraumatic osteomyelitis without a fracture. Weiland et al.127 in 1984 suggested another classification scheme based on the nature of the bony involvement. In this classification system, there were three types, with type I being characterized by open exposed bone without evidence of osseous infection, but with evidence of soft tissue infection. In type II fractures, there was circumferential cortical and endosteal infection, and in type III fractures, the cortical and endosteal infection was associated with a segmental defect. 
In 1989, May et al.71 proposed another classification scheme for osteomyelitis focusing on the tibia. This system was based on the nature of the bone following soft tissue and bony debridement. They proposed that there were five different categories. 
Type I posttraumatic tibial osteomyelitis was defined as being present when the intact tibia and fibula were able to withstand functional loads and no reconstruction was required. In type II osteomyelitis, the intact tibia was unable to withstand functional loading and required bone grafting. In type III osteomyelitis, there was an intact fibula but a tibial defect that measured no more than 6 cm. The tibial defect required cancellous bone grafting, tibiofibular synostosis, or distraction histogenesis. Type IV osteomyelitis was characterized by an intact fibula but with a defect of more than 6 cm in length, which required distraction osteogenesis, tibiofibular synostosis, or a vascularized bone graft. Type V osteomyelitis was characterized by a tibial defect of more than 6 cm without an intact fibula, which often required amputation. 
The Waldvogel classification125 categorized osteomyelitis into three primary etiologies—hematogenous, contiguous (from an adjacent root such as an open fracture or a seeded implant), or chronic, this being a long-standing osteomyelitis with mature host reaction. 
These various classification systems were predicated on the beliefs and treatment options of the times, and they have all become less relevant with current diagnostic and treatment modalities. However, each classification represented an important effort to categorize the pathophysiology of bone infection to facilitate the choice of an effective treatment. 
The currently accepted classification remains the Cierny–Mader classification,20 which not only describes the pathology in the bone, but more importantly, also classifies the host or patient (Tables 26-1 and 26-2). The usefulness of the Cierny–Mader system is its applicability to clinical practice and the wealth of experience and data gleaned from a single surgeon’s practice with meticulous records. The hallmark of Cierny’s and Mader’s approach is the use of oncologic principles for treatment. In fact, osteomyelitis behaves very similarly to a benign bone tumor in that it is rarely lethal but has a tendency to return without complete eradiation. Interestingly, the outcome data reported by Cierny et al.20 indicate that once appropriate surgical treatment is undertaken, the host may be the most important variable affecting treatment and outcome. 
 
Table 26-1
Cierny–Mader Classification of Bone
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Table 26-1
Cierny–Mader Classification of Bone
Type I—Medullary
Infection is limited to the medullary canal. Typically seen after intramedullary nailing.
Osseous Location  

 

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Involvement  

 

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Type II—Superficial
Infection is limited to the exterior of the bone and does not penetrate the cortex. Typically seen from pressure ulcers.
 

 

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Type III—Permeative/Stable
Infection penetrates cortex but bone is axially stable and generally will not require supplemental stabilization. Typically seen after internal fixation with plates.
 

 

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Type IV—Permeative/Unstable
Infection is throughout the bone in segmental fashion and results in axial instability. Typically seen in extensive infections or after aggressive debridement of type III infections that results in loss of axial stability.
 

 

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Table 26-2
Cierny–Mader Classification of the Host
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Table 26-2
Cierny–Mader Classification of the Host
Host Class Description
A host Healthy physiology and limb
B host: Systemic Diabetes, stable multiple organ disease, nicotine use, substance abuse, immunologic deficiency, malnutrition, malignancy, old age, vascular disease
Trauma context: Multiple injuries
B host: Local Previous trauma, burns, previous surgery, vascular disease, cellulitis, scarring, previous radiation treatment, lymphedema
Trauma context: Zone of injury
B host: Systemic/local Combinations of systemic and local conditions
C host Multiple uncorrectable comorbidities. Unable to tolerate the extent of surgical reconstruction required. Treatment of the disease is worse than the disease itself
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The hallmark of the Cierny–Mader classification is its analysis of the physiologic state of the patient or host. The host is classified by the number of systemic and local comorbidities. An A host has a healthy physiology and limb with little systemic or local compromise. The B host is further divided into one with local compromise (B local), systemic compromise (B systemic), or both (B systemic/local systemic compromise, which includes any immunocompromised condition, poor nutrition, diabetes, old age, multiple trauma, chronic hypoxia, vascular disease, malignancy, or organ failure such as renal insufficiency or liver failure). Local compromise includes conditions such as previous surgery or trauma, cellulitis, radiation fibrosis, scarring from burns or trauma, local manifestations of vascular disease, lymphedema, or zone-of-injury issues. We believe that a new variable of compromise can be identified in the trauma patient where systemic compromise is because of multiple organ damage, and the consequent systemic response to trauma and local compromise is defined by the zone-of-injury effects on local tissues. 
The C host is a patient in whom the morbidity of treatment is greater than the morbidity of disease because of multiple and severe comorbid conditions that cannot be treated safely. In these patients, the risks of curative treatment such as extensive surgery, as might be used with free flaps, or prolonged reconstruction with bone transport would be greater than that caused by the infective condition itself. Type C hosts are often better treated with limited nonablative surgery and suppression or, if appropriate, by an amputation. 
In the Cierny–Mader classification,20 the bone lesion is classified by the extent of involvement and stability. Type I is a medullary or endosteal infection without penetration through cortex. This is the type of infection that occurs after intramedullary nailing. Type II is a superficial osteomyelitis that involves only the outer cortex and is frequently contiguous with a pressure ulcer or adjacent abscess. Type III is permeative in that there is involvement of both cortical and medullary bone, but importantly, there is no loss of axial stability of the bone. Type IV also involves cortical and medullary bone but in a segmental fashion such that axial stability is lost. Types III and IV would be typical infections related to open fractures. In type IV lesions, the segmental resection that is required necessitates reconstruction of the bone, whereas in type III lesions, additional stabilization may not be required (Tables 26-1 and 26-2). 
The pairing of the four types of osteomyelitis with the three host classes allows for the development of practical treatment strategies. Cierny et al.20 proposed a detailed treatment regimen defining optimal treatment modalities for each stage. They achieved an overall clinical 2-year success rate of 91% for all states. As one would expect, when their results were broken down by class of host and type of lesion, Class A hosts fared the best. In class A hosts, success rates of 98% were achieved even with type IV osteomyelitis. The compromised class B host’s success rates were far lower, ranging from 79% to 92% depending on anatomic type. In his series, Cierny found that the host class seemed to be more important than the type of infection. A cumulative success rate of greater than 90% was achieved with most of the failures being in B hosts. C hosts were recommended for amputation or suppressive treatment.19 The lessons that stem from their findings are that it is important not just to treat the disease but also the host and that the patient’s physiologic condition should be optimized. Thus, a B systemic-local host who has had a previous open fracture but also smokes and has uncontrolled diabetes, renal insufficiency, and malnutrition should have all of these problems treated together with the bone disease. Improving host status would appear to be a fruitful endeavor when one considers Cierny et al.’s19,20 findings. 
It should be noted that Cierny et al.’s19,20 results used outcome criteria that were commonly used at that time. Current outcome studies focus more on subjective patient-based assessments than on surgeon-based assessments. We do not have much data on the functional outcomes in the scenarios described by Cierny et al., and it is possible that some of the patients whom they salvaged would have fared better with prosthetic replacement and vice versa. 

Pathogenesis

Before a discussion of diagnosis and treatment, it is vital to understand the mechanisms by which infections occur. Most infections encountered in orthopedics are related to biofilm-forming bacteria. Much of our understanding of biofilm bacteria has come from the Centre for Biofilm Engineering in Bozeman, Montana. Biofilm bacteria are also important in the oil, food processing, naval, paper manufacturing, and water processing industries. 
Biofilm bacteria exist in one of two states—the planktonic state or the colonized state (Fig. 26-1). Planktonic state bacteria are free floating in the blood stream and are isolated and relatively small in quantity. In this state, the body host defenses can easily eradicate the organism through the usual immunologic mechanisms. It is rare for planktonic bacteria to survive long in the blood stream despite numerous and repeated occurrences of entry. However, if the bacterial load is large and sustained, they can overwhelm the host defenses and escape the effects of antibiotics with the ensuing bacteremia leading to septicemia and death. Planktonic bacteria are also metabolically active and reproductive. This is an important consideration for antibiotic treatments that work by either interfering with cell wall or protein synthesis or with reproduction. 
Figure 26-1
Illustration of the process of biofilm bacterial colonization.
 
Firstly the bacteria need to find an inert surface such as an implant or dead tissue to attach to. Growth then occurs and the colonization process will continue until mature colonies are formed. Once mature, the colonies can detach depending on environmental signals or signals between colonies (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
Firstly the bacteria need to find an inert surface such as an implant or dead tissue to attach to. Growth then occurs and the colonization process will continue until mature colonies are formed. Once mature, the colonies can detach depending on environmental signals or signals between colonies (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
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Figure 26-1
Illustration of the process of biofilm bacterial colonization.
Firstly the bacteria need to find an inert surface such as an implant or dead tissue to attach to. Growth then occurs and the colonization process will continue until mature colonies are formed. Once mature, the colonies can detach depending on environmental signals or signals between colonies (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
Firstly the bacteria need to find an inert surface such as an implant or dead tissue to attach to. Growth then occurs and the colonization process will continue until mature colonies are formed. Once mature, the colonies can detach depending on environmental signals or signals between colonies (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
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If planktonic bacteria encounter a suitable inert surface such as dead or necrotic tissue, foreign bodies, or any avascular body part by either direct contamination, contiguous spreading, or hematogenous seeding, they can attach and begin the process of colonization. Juxtaposition of the bacteria with a surface or biomaterial is accomplished by van der Waals forces, which allow bacteria to develop irreversible cross-links with the surface (adhesion–receptor interaction).26 Adhesion is based on time-dependent specific protein adhesion–receptor interactions, as well as carbohydrate polymer synthesis in addition to charge and physical forces.59 Following adhesion to a surface, bacteria begin to create a mucopolysaccharide layer called biofilm or slime. They then develop into colonies. These colonies exhibit remarkably resilient behavior. Figure 26-2 illustrates mature biofilm colonies where pillars of a mature biofilm are visibly distributed on top of a monolayer of surface-associated cells. In addition to fixed cells, there are motile cells, which maintain their association with the biofilm for long periods, swimming between pillars of biofilm-associated bacteria.126 The interaction of the colonies and bacteria demonstrates complex communication via proteins or markers that can alter bacterial behavior. 
Figure 26-2
Illustration of biofilm colonies and interactions (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
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In the early stages of colonization, sessile bacteria can be killed or neutralized by the host defenses. However, some of these bacteria may escape destruction and potentially act as a nidus for future infection. Transition from colonization to infection usually requires other conditions to exist. This might occur if there was an inoculum that was larger than threshold levels, impaired host immune defense mechanisms, traumatized or necrotic tissues, a foreign body, or an acellular or inanimate surface such as dead bone, cartilage, or biomaterials. These complex mechanisms help explain why every open fracture or infected implant does not result in osteomyelitis. 
As previously discussed, the first step in the transition from colonization to infection requires bacterial adhesion, which will usually not occur on viable tissue surfaces. Thus, when foreign material or dead tissue is found in the body, a “race for the surface” begins. Host cells will attempt to incorporate nonliving material or sequester nonviable tissue via encapsulation so that a well-incorporated biomaterial implant that has such a tissue-integrated neocapsule will be resistant to bacterial adhesion. Furthermore, the same tissue integration can often isolate bacteria that have become sessile on an implant surface by sequestering the bacteria from necessary nutrients until host mechanisms can act. 
However, if bacteria encounter the surface and develop mature colonies, tissue integration by the host may be impaired and the process of infection may proceed. Damaged bone, necrotic tissues, and implants can act as a suitable surface for bacterial adhesion and colonization.69 Devitalized bone devoid of normal periosteum presents a collagen matrix to which bacteria can bind. Moreover, it has been suggested that bone sialoprotein can act as a ligand for bacterial binding to bone.69 Biomaterials and other foreign bodies are usually inert and susceptible to bacterial colonization because they are inanimate. Regardless of how inert a metal is, it may still modulate molecular events on its surfaces, these being receptor–ligand interactions, covalent bonding, and thermodynamic interactions.44,50 The most important feature of any particular method is the interaction between its outer surface atomic layer and the glycoproteins of prokaryotic and eukaryotic cells. Stainless steel and cobalt–chromium and titanium alloys are resistant to corrosion because of several mechanisms including surface oxide passivations. These surface oxides form a reactive interface with bacteria that can promote colony formation. There is therefore a balance between implanting devices with surface structures that lower the corrosion rates but might increase the likelihood of surface binding by bacteria. Thus, a large surface area and bacterial inoculum, combined with local tissue damage and a compromised or insufficient host response, can collectively create the necessary conditions for infection. 
Following bacterial adherence and colonization, the resistance to antibiotics appears to increase.85,86 This resistance is dependent on the type of surface to which the organisms are attached. Organisms that adhere to hydrocarbon polymers are extremely resistant to antibiotics. These same organisms, when attached to metals, do not resist antibiotic therapy to the same extent. Bacterial colonies can undergo phenotypic changes and appear to hibernate. They can survive in a dormant state without causing infection, and this can explain the recovery of bacteria from asymptomatic hardware removal.81 So, whereas colonization is a necessary antecedent for infection, colonization alone does not necessarily lead to infection. 
Two characteristics of colonized bacteria may help understand and explain this pseudoresistance. Because the passage of antibiotics through tissues is based on a diffusion gradient, colonized bacteria are insulated with a natural barrier of glycocalyx, often referred to as slime, through which the circulating antibiotic must diffuse before arriving at the bacterial cell wall (Fig. 26-3). The antibiotic molecules must then diffuse into the bacterial cell or be transported by metabolically active bacterial cell membranes. Because it is theorized that bacteria within biofilms have a decreased metabolic rate and undergo phenotypic changes, active processes such as cell membrane formation, which are targeted by antibiotics, would be similarly decreased (Fig. 26-4).117 Consequently, antibiotic concentrations of 1,500 times normal may be required to penetrate both the biofilm and the bacterial cell wall. Even then, most antimicrobials work via interference with cell wall synthesis or cellular reproduction, and they therefore require metabolically active bacteria to be effective. Thus, bacteria in the biofilm may be dormant and appear to be pseudoresistant. The more metabolically inactive the bacteria, the less bactericidal will be the antibiotic therapy, which is why mature or chronic infections can rarely be cured with antibiotics alone. Table 26-3 outlines the major antibiotic classes and their mechanisms of action, all of which may be limited by the bacterial state in biofilm. 
Figure 26-3
Illustration demonstrating the resistance to diffusion through biofilm for systemic antibiotics (from Center for Biofilm Engineering Montana State University—Bozeman, with permission).
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Figure 26-4
The phenomenon of “pseudoresistance.”
 
Biofilm bacteria can reduce their metabolic activity. Because many antibiotics interfere with such metabolic activity as their mechanism of action, any such attenuation may render antibiotics less effective. (From Center for Biofilm Engineering Montana State University—Bozeman, with permission.)
Biofilm bacteria can reduce their metabolic activity. Because many antibiotics interfere with such metabolic activity as their mechanism of action, any such attenuation may render antibiotics less effective. (From Center for Biofilm Engineering Montana State University—Bozeman, with permission.)
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Figure 26-4
The phenomenon of “pseudoresistance.”
Biofilm bacteria can reduce their metabolic activity. Because many antibiotics interfere with such metabolic activity as their mechanism of action, any such attenuation may render antibiotics less effective. (From Center for Biofilm Engineering Montana State University—Bozeman, with permission.)
Biofilm bacteria can reduce their metabolic activity. Because many antibiotics interfere with such metabolic activity as their mechanism of action, any such attenuation may render antibiotics less effective. (From Center for Biofilm Engineering Montana State University—Bozeman, with permission.)
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Table 26-3
Major Antibiotic Classes and Their Mechanism of Action
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Table 26-3
Major Antibiotic Classes and Their Mechanism of Action
Inhibition of cell wall synthesis/development Penicillin, cephalosporins, vancomycin, bacitracin, chlorhexidine
Inhibition of protein synthesis Chloramphenicol, macrolides, lincosamides, tetracyclines
Inhibition of RNA synthesis Rifampin
Inhibition of DNA synthesis Quinolones, macrolides
Inhibition of enzymatic/metabolic activity Trimethoprim/sulfamethoxazole (blocks folic acid production)
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Once colonization occurs, body defenses continue to identify bacteria as foreign. There may be chemotactic mechanisms that keep immune cells active. The subsequent collection of inflammatory cells brought in to wall off the bacteria via chemotaxis manifests as purulence, which is a symptom of the host’s attempt to isolate and destroy the infection. The acute inflammatory cells will also release a spectrum of oxidative and enzymatic products in an attempt to penetrate the glycocalyx. These mediators and enzymes are nonspecific and may be toxic to host tissue. Increased host tissue damage can lead to more surface substrate for local bacteria, creating a cycle of tissue damage, host response, and exacerbation of infection (Fig. 26-5). The host tissues will eventually react to limit the spread of infection macroscopically as well as microscopically. The clinical manifestation of a sequestered infection is an abscess or involucrum. Alternatively, if the infection grows and reaches the skin or an internal epithelial surface, a sinus tract forms as a route to dispel detritus. Although the appearance of a sinus tract is a manifestation of a locally devastating disease process and indicates severe underlying infection, it should be remembered that it may also prevent the accumulation of internal fixation, which can lead to bacteremia and septicemia. 
Figure 26-5
Autoinjury mechanism of host white cells in response to biofilm bacteria.
 
A: Host white cells engulf planktonic bacteria and then (B) moves to engulf a bacterial colony that has developed but is unable to do so. C: Host white cells next response to engulfed bacteria is to release oxidative enzymes, but those enzymes also cause damage to local host cells. D: Unsuccessful eradication of bacteria and colony growth attracts more host white cells, resulting in increased damage to host tissue.
A: Host white cells engulf planktonic bacteria and then (B) moves to engulf a bacterial colony that has developed but is unable to do so. C: Host white cells next response to engulfed bacteria is to release oxidative enzymes, but those enzymes also cause damage to local host cells. D: Unsuccessful eradication of bacteria and colony growth attracts more host white cells, resulting in increased damage to host tissue.
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Figure 26-5
Autoinjury mechanism of host white cells in response to biofilm bacteria.
A: Host white cells engulf planktonic bacteria and then (B) moves to engulf a bacterial colony that has developed but is unable to do so. C: Host white cells next response to engulfed bacteria is to release oxidative enzymes, but those enzymes also cause damage to local host cells. D: Unsuccessful eradication of bacteria and colony growth attracts more host white cells, resulting in increased damage to host tissue.
A: Host white cells engulf planktonic bacteria and then (B) moves to engulf a bacterial colony that has developed but is unable to do so. C: Host white cells next response to engulfed bacteria is to release oxidative enzymes, but those enzymes also cause damage to local host cells. D: Unsuccessful eradication of bacteria and colony growth attracts more host white cells, resulting in increased damage to host tissue.
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Eventually, an equilibrium may exist in the form of a chronic infection, which is what many surgeons see in practice. There is usually a history of intermittent symptoms and drainage that has responded to some type of antibiotic regimen. What this probably represents is the inhibition of colony expansion at the borders of the infectious site. Clinically harmful manifestations of infection are generally caused by the release of bacteria into the bloodstream that are metabolically active and release toxins in addition to the release of oxidative enzymes by the host cell. Although the bacteria remain susceptible to the body’s host defenses and to antibiotics, their numbers and continued release into the bloodstream represent a chronic debilitating disease. Any acute stress on the host environment from trauma, disease, or immunosuppression can allow the infection to strengthen and spread. Thus, long-standing infections that were tolerated by young healthy individuals may suddenly become limb- or life-threatening as the individuals age. 
New developments stemming from the work of the Bozeman group provide novel opportunities to treat bacterial infection of orthopedic implants. These include surface coatings, agents that inhibit colonization or promote dissolution of colonies, small electric fields, and low pH and acidic and negatively charged surfaces that are resistant to biofilms. Surface properties of implants or local or systemic drugs may help decrease the risk to infection, particularly in the elderly population, who have decreased immune system activity. 

Infection after Fracture

Infection after fracture is most likely to be associated with open fractures or invasive surgical procedures. Few closed fractures treated nonoperatively develop osteomyelitis. To improve the diagnosis of posttraumatic bone infection, it is necessary to understand the mechanisms of infection, particularly for open fractures. 
Approximately 60% to 70% of open fractures are contaminated by bacteria, but a much smaller percentage develops infection. The risk of infection correlates significantly with the degree of soft tissue injury.121 If one remembers that merely the presence of bacteria in an open wound is not sufficient to cause infection, it is important to recognize that a severely contaminated fracture can rarely be debrided to the point of achieving a sterile or bacteria-free tissue bed. We believe that next to removing the majority of bacteria from the contaminated tissue bed, the second major goal of a wide and aggressive debridement is to leave behind a viable tissue bed with minimal necrotic or inert surfaces for the remaining bacteria to colonize. By minimizing the bacterial contamination by eliminating adhesions and nutrition, the host gains an opportunity to eradicate any remaining contaminants in the zone of injury. Figure 26-6 demonstrates the concept of open fracture debridement where a contaminated wound is debrided until the remaining wound looks as if it is created surgically, with residual tissue being healthy with little evidence of contamination. It is important to remember that contamination can penetrate into tissue planes or locations that are not obvious in the initial wound. This may be a particular problem with blast injuries. The use of pulsatile irrigation before surgical exploration and debridement may in fact push the initial contaminants deeper into the tissues and result in contaminants being left behind in a locally compromised tissue bed. This will increase the likelihood of both acute and delayed infection. 
Figure 26-6
Operative photographs of a severe open tibial fracture.
 
A: The appearance before surgical debridement. B: The appearance after surgical debridement. Note that after debridement the tissues and wound appear to have been made surgically. Although it is unlikely that all bacteria have been removed, a thorough exploration and debridement, leaving only viable tissues, will minimize the risk of subsequent infection.
A: The appearance before surgical debridement. B: The appearance after surgical debridement. Note that after debridement the tissues and wound appear to have been made surgically. Although it is unlikely that all bacteria have been removed, a thorough exploration and debridement, leaving only viable tissues, will minimize the risk of subsequent infection.
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Figure 26-6
Operative photographs of a severe open tibial fracture.
A: The appearance before surgical debridement. B: The appearance after surgical debridement. Note that after debridement the tissues and wound appear to have been made surgically. Although it is unlikely that all bacteria have been removed, a thorough exploration and debridement, leaving only viable tissues, will minimize the risk of subsequent infection.
A: The appearance before surgical debridement. B: The appearance after surgical debridement. Note that after debridement the tissues and wound appear to have been made surgically. Although it is unlikely that all bacteria have been removed, a thorough exploration and debridement, leaving only viable tissues, will minimize the risk of subsequent infection.
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An important fact that is often unrecognized is that the bacteria recovered from clinical infections are not necessarily the bacteria found acutely in the contaminated tissue bed. Several studies have found that routine cultures of open fractures are not useful because the predominant organism recovered from acute cultures is frequently not the organism recovered if and when an infection occurs. Antibiotic treatment based on the acute culture, whether before or after debridement, may be detrimental because the antibiotic that is chosen may not be specifically indicated and has the potential to promote changes and overgrowth in the bacterial flora. In the worst case scenario, routine antibiotic treatment based on initial wound cultures may promote the development of resistant bacterial strains.64,92,122 
Many of the organisms responsible for eventual osteomyelitis are often hospital-acquired pathogens such as resistant Staphylococcus aureus or gram-negative bacilli, including Pseudomonas aeruginosa,51,67 which are not initially present in a traumatic wound. This does not mean that other bacteria should not be considered and these may depend on the environment. Clostridium perfringens must be considered if there is soil contamination and Pseudomonas, and Aeromonas hydrophila may be present following a freshwater injury. Vibrio and Erysipelothrix may be present in saltwater injuries. One possible explanation for the lack of correlation between acute cultures and the eventual infection may be that the initial contaminants are of low virulence and easily neutralized by a combination of debridement and antibiotics, but that the locally and, in polytrauma, the systemically, compromised tissue bed is susceptible to the more aggressive nosocomial organisms. 

Acute Posttraumatic Osteomyelitis

Acute posttraumatic osteomyelitis is a bone infection that results in traumatic injury that allows pathogenic organisms to make contact with damaged bone and soft tissues, with a proliferation and expression of infection.75 In a patient with traumatic injuries, additional factors that contribute to the subsequent development of osteomyelitis are the presence of hypotension, inadequate debridement of the fracture site, malnutrition, sustained intensive care unit hospitalization, alcoholism, and smoking.41,118 Trauma may lead to interference with the host response to infection. Tissue injury or the presence of bacteria triggers activation of the complement cascade that leads to local vasodilatation, tissue edema, migration of polymorphonuclear leukocytes (PMNs) to the site of the injury, and enhanced ability of phagocytes to ingest bacteria.56 Trauma has been reported to delay the inflammatory response to bacteria as well as to depress cell-mediated immunity and to impair the functions of PMNs, including chemotaxis, superoxide production, and microbial killing.56 The commonly used system of Cierny–Mader20 has been shown to have a close correlation with the general condition of the patient rather than the specifics of bone involvement. 

Chronic Osteomyelitis

This condition is often the result of an acute osteomyelitis that is inadequately treated. General factors that may predispose to chronic osteomyelitis include the degree of bone necrosis, poor nutrition, the infecting organism, the age of the patient, the presence of comorbidities, and drug abuse.25 The infecting organism generally varies with the cause of the chronic osteomyelitis. Chronic osteomyelitis results from acute osteomyelitis and is frequently caused by S. aureus, although chronic osteomyelitis that occurs after a fracture can be polymicrobial or gram negative. Intravenous drug users are commonly found to have Pseudomonas as well as S. aureus infections. Gram-negative organisms are now seen in up to 50% of all cases of chronic osteomyelitis, and this may be because of variables such as surgical intervention, chronic antibiotics, nosocomial causes, or changes in the bacterial flora of the tissue bed.25 The fundamental problem in chronic osteomyelitis is a slow progressive revascularization of bone that leaves protected pockets of necrotic material to support bacterial growth that are relatively protected from systemic antibiotic therapy. This collection of necrotic tissue, bone, and bacteria is what becomes termed a sequestrum, and the body’s attempt to wall off the offending material with reactive inflammatory tissue, whether this is bone or soft tissue, is termed the involucrum. The involucrum can be highly vascular and may be viable and structural, and this should be taken into consideration during surgical debridement. 

Fungal Osteomyelitis

Fungal osteoarticular infections are caused by two groups of fungi. The dimorphic fungi, which include Blastomyces dermatitidis, Coccidioides sp., Histoplasma capsulatum, and Sporothrix schenckii, typically cause infections in healthy hosts in endemic regions, whereas Candida sp., Cryptococcus, and Aspergillus cause infections in immunocompromised hosts. Infection is introduced by direct trauma or injury but may be associated with a penetrating foreign body or hematogenous spread. 
Candida sp. is the most common fungus seen in osteomyelitis. It affects both native and prosthetic joints, vertebrae, and long bones. Risk factors include loss of skin integrity, diabetes, malnutrition, immunosuppressive therapy, intravenous drug use, hyperalimentation, the use of central venous catheters, intra-articular steroid injections, and the use of broad-spectrum antibiotics. A combined approach to therapy using medical and surgical modalities is necessary for optimal results. Azole antifungals and lipid preparations of amphotericin B have expanded the therapeutic options in fungal osteomyelitis as there is reduced toxicity associated with long-term therapy.75 

Clinical and Laboratory Diagnostic Tests

A history of infection or intercurrent illness as well as of remote surgery or trauma should raise the clinical suspicion of osteomyelitis. Normal signs of inflammation may be absent and thus the diagnosis of infection may be difficult. Patients may have a history of infection at another site, such as the lungs, bladder, or skin in conjunction with a history of trauma. They usually complain of pain in the affected area and feel generally unwell. Moreover, reduced activity, malaise, anorexia, fever, tachycardia, and listlessness may be present. Local findings include swelling and warmth, occasional erythema, tenderness to palpation, drainage, and restricted range of motion in adjacent joints. 
Aspects of the clinical history that should alert the surgeon to look for infection include a history of open fracture, severe soft tissue injury, a history of substance abuse and smoking, inadequate previous treatment, or an immunocompromised state. These are all factors that contribute to a B host. Factors affecting treatment that need to be assessed include the time of onset of the infection, the status of the soft tissues, the viability of the bone, the status of fracture healing, implant stability, the condition of the host, and the neurovascular examination. 
Routine blood cultures are of little help unless patients show manifestations of systemic disease, but they may be positive in up to 50% to 75% of cases where there is concomitant bacteremia or septicemia.128 Blood cultures that yield coagulase-negative staphylococci, a common contaminant and pathogen, must be correlated with other clinical findings before attribution of clinical significance. Blood results that are suggestive of infection include an elevation of the white blood cell (WBC) count and elevations in the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. The ESR may be normal in the first 48 hours, but rises to levels about 100 mm/hr and may remain elevated for several weeks. It is, however, a nonspecific marker.128 Combination of the ESR with the CRP improves specificity such that if both are negative, the specificity is 90% to 95% for acute osteomyelitis. In other words, a negative CRP and ESR make osteomyelitis unlikely. Their values are also age-dependent, and there is a steady increase in normal values with aging. In one recent study, the ESR and CRP were found to be useful diagnostic tools for the detection of an infected arthroplasty. Although they had low sensitivities and positive predictive values and therefore were of little value for screening, they had high specificity and negative predictive value and therefore were useful for treatment decisions.49 These studies and other diagnostic studies may not be as useful in acute postoperative and chronic infections. In the acute setting, the ESR and CRP are expected to be elevated because of local and systemic inflammation from the surgical procedure. In chronic infections, the host has had time to adapt to the offending condition and thus may not mount the response required to trigger an elevation in these tests. Once osteomyelitis treatment is initiated, the CRP and ESR are useful in following the response to treatment. We use the ESR and CRP to establish a baseline value before debridement and initiation of antibiotic therapy and to monitor the subsequent response to treatment. 

Radiographic Imaging

Radiologic findings in the initial presentation of acute osteomyelitis are often normal. The most common radiographic signs of bone infection are rarefaction, which represents diffuse demineralization secondary to inflammatory hyperemia; soft tissue swelling with obliteration of tissue planes; trabecular destruction; lysis; cortical permeation; periosteal reaction; and involucrum formation. Radiologically detectable demineralization may not be seen for at least 10 days after the onset of acute osteomyelitis.128 When present, mineralization usually signifies trabecular bone destruction. If the infection spreads to the cortex, usually within 3 to 6 weeks, a periosteal reaction may be seen on radiographs. One study reported that in cases of proven osteomyelitis, 5% of radiographs were abnormal initially, 33% were abnormal by 1 week, and 90% were abnormal by 4 weeks.6 In trauma and fracture treatment, the nature of callus formation and the obfuscation of bone by hardware may make radiologic changes difficult to recognize in the early or middle states of infection. Often it is not until there is a clear sequestrum, sinus, or involucrum that parallels the clinical findings that specific radiographic changes are recognized (Fig. 26-7). 
Figure 26-7
A radiograph showing the changes seen in bone with osteomyelitis.
 
Note the periosteal reaction and the permeative changes in the bone.
Note the periosteal reaction and the permeative changes in the bone.
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Figure 26-7
A radiograph showing the changes seen in bone with osteomyelitis.
Note the periosteal reaction and the permeative changes in the bone.
Note the periosteal reaction and the permeative changes in the bone.
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Bone Scintigraphy

Scintigraphy has been widely used and remains a very useful diagnostic tool. However as noted below the usefulness of this test is governed by a number of variables such as technique and reader accuracy and the mainstay of diagnosis remains the clinical history together with the common screening examinations of CRP and ESR. There are numerous types of scintigraphy, but three scan types are commonly used to diagnose musculoskeletal infection. These are the bone scan, which uses tagged red cells; the leukocyte scan, which uses tagged white cells; and the bone marrow scan, which investigates marrow cell activity. Recently, positron emission tomography (PET) has shown promise and is undergoing increased investigation and use. 
Technetium-99m is the principal radioisotope used in most whole-body red cell bone scans.27,31,31 Technetium is formed as a metastable intermediate during the decay of molybdenum-99. It has a 6-hour half life and is relatively inexpensive and readily available.31 After intravenous injection, there is a rapid distribution of this agent throughout the extracellular fluid. Within several hours, more than half the dose will accumulate in bone, whereas the remainder is excreted in the urine. Technetium phosphates bind to both the organic and inorganic matrix. However, the key characteristic that makes technetium scanning useful is that there is preferential incorporation into metabolically active bone. Bone images are usually acquired 2 to 4 hours following intravenous injection of the isotope. A triple-phase bone scan is one that is useful for examining general inflammation and related processes. Following the initial injection, dynamic images are captured over the specified region. These are followed by static images at later time points. The first phase represents the blood flow phase, the second phase immediately post injection represents the bone pooling phase, and the third phase is a delayed image made at 3 hours when there is decreased soft tissue activity. Classically, osteomyelitis presents as a region of increased blood flow, and it should appear “hot” in all phases with focal uptake in the third phase (Fig. 26-8). Other processes such as healing fractures, loose prostheses, and degenerative change do not appear hot in the early phase despite a hot appearance in the delayed phase. Reported sensitivities of bone scintigraphy for the detection of osteomyelitis vary considerably from 32% to 100%. Reported specificities have ranged from 0% to 100%.106,124 
Figure 26-8
A standard bone scan demonstrating increased activity in the distal femur.
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Gallium-67 citrate binds rapidly to serum proteins, particularly transferrin.10,102 There is also uptake in the blood, especially by leukocytes. Gallium has been used in conjunction with technetium-99 to increase the specificity of the bone scanning.39,52 Several mechanisms have been postulated to explain the increased activity at sites of inflammation. Enhanced blood flow and increased capillary permeability cause enhanced delivery. Bacteria have high iron requirements and thus take up gallium. Gallium is strongly bound to bacterial siderophores and leukocyte lactoferrins. In regions of inflammation, these proteins are available extracellularly and can avidly bind with gallium. Chemotaxis also acts to localize gallium-labeled WBCs at the sites of infection. In a typical study, gallium is injected intravenously and delayed images are acquired at 48 to 72 hours. The hallmark of osteomyelitis is the focal increased uptake of gallium. Unfortunately, gallium’s nonspecific bone uptake can be problematic because any processes causing reactive new bone formation will appear hot. In patients with fractures or a prosthesis, osteomyelitis cannot be easily diagnosed with gallium alone. Gallium images are usually interpreted in conjunction with a technetium bone scan. Gallium activity is interpreted as abnormal either if it is incongruous with the bone scan activity or if there is a matching pattern with gallium activity. Reported sensitivities and specificities for the diagnosis of osteomyelitis range from 22% to 100% and 0% to 100%, respectively.27,52,77,106 Despite its lower-than-optimal diagnostic value, gallium still has some advantages. It is easily administered and it is the agent of choice in chronic soft tissue injection, although it is less effective in bone infections. It has also proved useful in following the resolution of an inflammatory process by showing a progressive decline in activity. 
An indium-111 or 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) (Ceretec; GE Healthcare) labeled leukocyte scan is the most common scan used in conjunction with a standard bone scan. The labeled leukocytes migrate to the region of active infection resulting in a hot white cell scan over the area of active inflammation. The use of a combined red cell and white cell scan significantly increases both the sensitivity and specificity and now represents the gold standard of radionuclide testing for infection.68 Because of the variable accuracy of both technetium and gallium scans most laboratories routinely use 111 In-labeled leukocytes.102,105,109,123 Indium WBC preparations require the withdrawal of approximately 50 mL of autologous whole blood with a leukocyte count of at least 5,000 cells/mm3. The leukocytes are labeled with 1 mCi of indium oxine and then reinjected. They redistribute in the intravascular space. Immediate images show activity in the lungs, liver, spleen, and blood pool. The half life is about 7 hours. After 24 hours, only the liver, spleen, and bone marrow show activity. Wounds that heal normally and fully treated infections show no increase in uptake. Leukocytes that migrate to an area of active bone infection will show increased uptake (Fig. 26-9). Most results show improved sensitivity (80% to 100%) and specificity (50% to 100%) for the diagnosis of osteomyelitis.2830,54,58 Indium-labeled WBC scans are generally superior to bone scans and gallium scans in the detection of infection. McCarthy et al.73 reported on the use of indium scans in 39 patients who had suspected osteomyelitis confirmed by bone biopsy. They found indium scans to be 97% sensitive and 82% specific for osteomyelitis. The few false-positive results occurred in patients who had overlying soft tissue infections. An accompanying bone scan can help to differentiate bone infection from soft tissue infection. In these situations, the indium scan should be performed before the bone scan to avoid false-positive results. With both tests, the sensitivities and specificities are in excess of 90%. 
Figure 26-9
A white cell scan of the patient shown in Figure 26-8 demonstrating increased accumulation of tracer in the distal femur.
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Figure 26-9
A white cell scan of the patient shown in Figure 26-8 demonstrating increased accumulation of tracer in the distal femur.
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Until recently, a clinician investigating the site of infectious foci using nuclear medicine had a choice between 67Ga-citrate imaging and 111In-oxine leukocyte imaging.28 Scientific advances, especially in nuclear medicine, have increased these choices considerably. Several techniques in nuclear medicine have significantly aided the diagnosis of infection including imaging with 99mTc-HMPAO and 99mTc-stannous fluoride colloid-labeled leukocytes.58 The principal clinical indications for 99mTc-HMPAO leukocytes include osteomyelitis and soft tissue sepsis. Chronic osteomyelitis, including infected joint prostheses, is better diagnosed with 111In-labeled leukocytes.93 The use of 99mTc-HMPAO leukocyte scintigraphy in patients with symptomatic total hip or knee arthroplasty has shown improved diagnostic accuracy through the use of semiquantitative evaluation.129 
Sulfur colloid bone scanning is a newer modality that is being increasingly used for the diagnosis of infection. The scan evaluates the bone marrow activity in an area where infection is suspected. The marrow may be reactive in several conditions that are not infected and is generally suppressed when infection is present. With the use of microcolloid bone marrow scans, more information is available to increase the specificity of diagnosis. There is the possibility of leukocyte accumulation with certain inflammatory conditions that could result in a false-positive indium scan. An infection will tend to suppress marrow activity and thus render the marrow scan cold, whereas the white cell scan may still be hot (Fig. 26-10). If the white cell scan is as hot as the marrow scan, it is possible that an infection may not be present. Segura et al.112 examined technetium-labeled white cell scans (Tc-HMPAO) and technetium microcolloid marrow scans in total joint replacements. They found that in 77 patients, the white cell scans by themselves had a sensitivity of 96% and a specificity of 30%. When the colloid scan was added, the sensitivity decreased to 93% but the specificity increased to 98%. The addition of a regular red cell scan was not helpful.109 In another study by Palestro et al.,90 an indium-labeled white cell scan was compared with technetium sulfur colloid scans to differentiate infection from Charcot arthropathy. They found that white cell scans were positive in 4 of 20 cases, of which 3 were infected. In the 16 negative white cell scans, the marrow scan was also negative. However, in the four positive cases, the marrow scan was positive in two cases that were confirmed to be infected. They concluded that white cell scans can be positive in hematopoietically active bones, which can occur in the absence of infection, and that marrow scans should be used to confirm the diagnosis. 
Figure 26-10
A marrow scan of the patient shown in Figure 26-8 demonstrating suppression of marrow in distal femur.
 
Sulfur colloid scanning. Positive or “hot” scans indicate marrow activity and can be seen in inflammatory marrow conditions.
Sulfur colloid scanning. Positive or “hot” scans indicate marrow activity and can be seen in inflammatory marrow conditions.
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Figure 26-10
A marrow scan of the patient shown in Figure 26-8 demonstrating suppression of marrow in distal femur.
Sulfur colloid scanning. Positive or “hot” scans indicate marrow activity and can be seen in inflammatory marrow conditions.
Sulfur colloid scanning. Positive or “hot” scans indicate marrow activity and can be seen in inflammatory marrow conditions.
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Classically, a combination of red cell bone scan and a labeled leukocyte scan has been used. Because standard bone scan agents and gallium are usually both positive at fracture sites; they have limited value in the detection of infection following a fracture. With no discernible uptake in reactive bone, indium-labeled WBC scans are superior in the detection of infection following fracture. In a prospective study of 20 patients with suspected osteomyelitis together with delayed union, Esterhai et al.40 reported 100% accuracy of indium-labeled WBC scans. Seabold et al.110 have shown that the use of indium-labeled WBC scans and bone scans, to differentiate between soft tissue infections, can be 97% specific for osteomyelitis. In chronic or recurrent osteomyelitis, bone scans by themselves are of less value because they show increased uptake for 2 years following the successful treatment and resolution of infection.48 Although gallium scans have historically been shown to be successful in following the resolution of chronic osteomyelitis, indium-labeled WBC scans appear to be superior. Merkel et al.76 compared indium-labeled WBC and gallium scans in a prospective study of 50 patients. They found that indium-labeled WBC scans had an accuracy of 83% compared with 57% for gallium scans in the detection of osteomyelitis. However, it is important to remember that all clinical data, including a detailed clinical history, a characterization of the host, appropriate laboratory studies, clinical examination, and radiographic studies, are important in determining the likelihood and extent of infection. 
We have investigated the usefulness of these three scans read by a nuclear medicine specialist in a blinded fashion using receiver operating curves. We did not find any particular scan combinations that provided a reliable screening tool (sensitivity), but we did find that certain combinations provided good treatment decisions (specificity). Furthermore, the combination of white cell and marrow scans was equivalent to the combination of all three scans and better than the combination of red and white cell scans, which implies that the red cell scan may be of limited value. Whereas the sensitivities of all of these tests and combinations were low, the specificities remained at about 90% and the conclusion was that standard red cell scanning may not be necessary for the diagnosis of posttraumatic infection. Furthermore, we corroborated the findings of Segura et al.112 and found that the red cell scan added little. Unfortunately, surgeons often continue to base their suspicion of infection on a simple bone scan. Table 26-4 illustrates the matrix as a guide to assist the interpretation of bone scan combinations.22 
Table 26-4
Matrix of Scintigraphic Combinations and Potential for Infection
Scan Results (Activity)
Bone scan Cold Hot Hot Hot
White cell scan Cold Cold Hot Hot
Marrow scan Cold Cold Cold Hot
Infection present? No Unlikely Probably Maybe
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Other Scintigraphic Methods

In general, the accumulation of radiolabeled compounds and infectious conditions occurs via several routes. The labeled agents can bind to activate endothelium (anti-E-selectin). They can also enhance the influx of leukocytes or related by-products (autologous leukocytes, antigranulocyte antibodies, or cytokines), and they can enhance glucose uptake by activated leukocytes (F-fluorodeoxyglucose [FDG]).65 In addition, they bind directly to microorganisms (radiolabeled ciprofloxacin or antimicrobial peptides). Labeling of polyclonal immunoglobulin is a newer technique to investigate infection. It uses antigranulocyte antibodies, radiolabeled nonspecific human IgG, interleukins, and antimicrobial peptides.9 The nonspecific polyclonal IgG prepared from human serum gamma globulin can be labeled with various agents, including indium, gallium, or technetium, and can be used for the detection of osteomyelitis.9,95,102 Unlike labeled leukocyte scans, the IgG agent is easily prepared with short blood half lives of about 24 hours. The primary uptake occurs in the liver with less bone marrow uptake.75 Indium IgG scintigraphy is useful for the detection of musculoskeletal infection in patients in whom sterile inflammatory events stimulate infectious processes.79 However, despite its usefulness, this modality has not yet found its way into common clinical practice. 
PET with 18F-FDG has been shown to delineate various infective and inflammatory disorders with a high sensitivity. The FDG–PET scan enables noninvasive detection and demonstration of the extent of chronic osteomyelitis with 97% accuracy.32 PET scanning is especially accurate in the central skeleton within active bone marrow.31 Although not yet in widespread use, it may well prove to be the single most useful test in specifically diagnosing bone infection. In one study, the overall accuracy of FDG–PET in evaluating infection involving orthopedic hardware was 96.2% for hip prostheses, 81% for knee prostheses, and 100% in 15 additional patients with other orthopedic implants. In patients with chronic osteomyelitis, the accuracy is 91%.17 FDG–PET scanning appears to be a sensitive and specific method for the detection of infective foci because of metallic implants, which makes it useful in patients with trauma. Sensitivity, specificity, and accuracy were 100%, 93.3%, and 97%, respectively, for all PET data. The figures were 100%, 100%, and 100% for the central skeleton and 100%, 87.5%, and 95%, respectively, for the peripheral skeleton.107 PET scanning may soon become the preferred diagnostic modality for the diagnosing and staging of skeletal infections. 

Magnetic Resonance Imaging

MRI continues to play an important role in the evaluation of musculoskeletal infection.78,98,114 The sensitivity and specificity of MRI scans for osteomyelitis ranges from 60% to 100% and from 50% to 90%, respectively. MRI has the spatial resolution necessary to accurately evaluate the extent of infection in preparation for surgical treatment and particularly to localize abscess cavities. T1- and T2-weighted imaging is usually sufficient; fat suppression and short tau inversion recovery (STIR) sequences may be added to improve the imaging of bone marrow and soft tissue abnormalities. MRI also has the ability to differentiate between infected bone and involved adjacent soft tissue structures. Images can be acquired in any orientation and there is no radiation exposure. Occasionally, a sinus tract can be identified (Fig. 26-11). Gadolinium enhancement should be obtained in the postoperative population to better differentiate postsurgical artifact from infection-related bone marrow edema patterns. Gadolinium may differentiate abscess formation from diffuse inflammatory changes and noninfectious fluid collections. 
Figure 26-11
Magnetic resonance images of an infected tibia.
 
In (A) the sinus tract can be seen leading to a central sequestrum (white area in the intramedullary canal). In (B) there is contrast entering into a bone abscess.
In (A) the sinus tract can be seen leading to a central sequestrum (white area in the intramedullary canal). In (B) there is contrast entering into a bone abscess.
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Figure 26-11
Magnetic resonance images of an infected tibia.
In (A) the sinus tract can be seen leading to a central sequestrum (white area in the intramedullary canal). In (B) there is contrast entering into a bone abscess.
In (A) the sinus tract can be seen leading to a central sequestrum (white area in the intramedullary canal). In (B) there is contrast entering into a bone abscess.
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Active osteomyelitis characteristically displays a decreased signal in T1-weighted images and appears bright in T2-weighted images. The process presents the replacement of marrow fat with water from edema, exudates, hyperemia, and ischemia. However, the MRI signal characteristics that reflect osteomyelitis are intrinsically nonspecific, and tumors and fractures can also increase the marrow water content. In patients without prior complications, MRI has been found to be sensitive, but not specific, for osteomyelitis. When a fracture or prior surgery is evident, MRI is less specific in the diagnosis of infection. Furthermore, in the presence of metallic implants, artifacts make it difficult to comment on areas of interest that are near the implant. Certain external fixators are not compatible with MRI and thus will preclude its use. We have found that the best use of MRI is helping to determine the extent of the infection for preoperative planning. Our experience has been that using MRI to plan the degree of bone resection or debridement is helpful, but that MRI may lead to an overestimation of the extent of the infection because of the detection of adjacent edema. 

Computed Tomography

Computed tomography (CT) has assumed a lesser role in the evaluation of osteomyelitis with the widespread use of MRI.31 However, CT remains unsurpassed in the imaging of cortical bone. It is especially useful in delineating the cortical details in chronic osteomyelitis, such as sequestra and foreign bodies.115 CT is also useful in evaluating the adequacy of cortical debridement in the staged treatment of chronic osteomyelitis. Thus, it can help differentiate between type III and type IV infections. With modern equipment, CT scanning around fracture implants has improved and it can help evaluate both bone pathology and the extent of bone union. CT is also valuable in the treatment of extensive osteomyelitis in that it can determine the extent of bony involvement. In chronic cases, with some remodeling of both host and pathologic bone, it can often differentiate and identify sequestra or sclerosed diseased bone. It may often demonstrate useful pathologic findings (Fig. 26-12). 
Figure 26-12
 
A: Computed tomography images of the sinus shown in Figure 26-11A. There is evidence of cortical changes suggestive of a sequestrum. In (B) there is clear evidence of a sequestrum which is avascular and infected bone that has not undergone resorption and remains a surface for colonized bacteria to proliferate. Systemic and even local antibiotics would not be sufficient to eradicate infection at this stage.
A: Computed tomography images of the sinus shown in Figure 26-11A. There is evidence of cortical changes suggestive of a sequestrum. In (B) there is clear evidence of a sequestrum which is avascular and infected bone that has not undergone resorption and remains a surface for colonized bacteria to proliferate. Systemic and even local antibiotics would not be sufficient to eradicate infection at this stage.
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Figure 26-12
A: Computed tomography images of the sinus shown in Figure 26-11A. There is evidence of cortical changes suggestive of a sequestrum. In (B) there is clear evidence of a sequestrum which is avascular and infected bone that has not undergone resorption and remains a surface for colonized bacteria to proliferate. Systemic and even local antibiotics would not be sufficient to eradicate infection at this stage.
A: Computed tomography images of the sinus shown in Figure 26-11A. There is evidence of cortical changes suggestive of a sequestrum. In (B) there is clear evidence of a sequestrum which is avascular and infected bone that has not undergone resorption and remains a surface for colonized bacteria to proliferate. Systemic and even local antibiotics would not be sufficient to eradicate infection at this stage.
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Cultures and Biopsy

Identification of an organism and determination of antibiotic resistance patterns are crucial to a successful outcome in the management of osteomyelitis. With regard to open fractures, the issue of culturing the predebridement or postdebridement tissue bed is often discussed among surgeons and infectious disease specialists. In civilian wounds, gram-positive bacteria usually predominate at the time of injury, but frequently change to gram-negative bacteria, which are often the cause of late infections. In one study, 119 of 225 open fractures had positive wound cultures with only 8% of predebridement cultures correctly identifying the infecting organism, whereas 7% of those with negative predebridement cultures also developed infection. In only 22% did the postdebridement cultures correlated with the ultimate infecting organism. These data are clinically relevant because treating the wrong bacteria can promote overgrowth of the true infecting bacteria or add to the development of resistant organisms. In recent war experience, military surgeons have noted different bacteria flora causing infection, but the same principles still apply to their treatment.14,64,84,122 Although cultures of the sinus tract can be helpful, they should not be the sole guide for antibiotic treatment.40 A study by Moussa et al.82 found that 88.7% of sinus tract isolates were identical to operative specimens in 55 patients with chronic bone infection. However, other researchers have reported a concordance rate of between 25% and 45%.66 The ability to obtain true deep cultures of the sinus improves concordance, but it is still not helpful. One study concluded that nonbone specimens had a worse concordance than bone specimens and were associated with 52% false negatives and 36% false positives. It is important to recognize that not only the superficial cultures of sinus tracts, open wounds, and fractures are unhelpful but also an error in bacterial identification may lead to inappropriate antibiotic selection and ultimately compromise patient outcome. Bone biopsy remains the preferred diagnostic procedure in chronic osteomyelitis. Multiple specimens should be obtained if possible, not only to minimize sampling error but also to increase specificity and sensitivity. Histologic and microbiologic evaluation of percutaneous biopsy samples should be combined in cases of suspected osteomyelitis. The sensitivity of culture in the diagnosis of osteomyelitis can be improved from 42% to 84% by the addition of histologic evaluation. 

Molecular Diagnostics

Identification procedures based on molecular analysis and RNA or DNA typing are currently in development to facilitate diagnosis in osteomyelitis. These techniques offer a precise method of organism identification in cases in which standard techniques do not identify a pathogen despite the clinical presence of infection. This scenario is not uncommon in patients who have been treated with antibiotics shortly before sample collection. These methods target specific macromolecules unique to the infecting pathogens that are absent in the host cells.38,119 They have the potential to provide rapid results with high accuracy.57 The most commonly used method for the diagnosis of orthopedic infections is the polymerase chain reaction (PCR).57 This has been used to identify microremnants of bacteria by identifying their nuclear contents. Sequences within bacterial 16S ribosomal RNA have served as targets for amplification and detection.57 Unfortunately, PCR cannot easily delineate between nuclear materials from living or dead bacteria. This increases the likelihood of false-positive studies. Further investigations are required before these techniques can be widely used, as currently they lack sufficient sensitivity and specificity. However, their use remains promising. There have been recent reports of real-time testing that also appear more reliable and rapid, which could be very useful when deciding whether there is ongoing infection before undertaking a procedure requiring the implantation of orthopedic hardware.116 
A new screening technique for methicillin-resistant Staphylococcus aureus (MRSA), recently evaluated at an urban trauma center, directly examines bacterial DNA. It identifies the organisms, as well as their antibiotic sensitivities, with a multiplex polymerase chain reaction. Diatherix Laboratories (Huntsville, AL) provides a screening system that not only might avoid infection complications in trauma patients but also provide documentation that infections during the hospital stay were because of prehospital MRSA colonization. A review of 332 patients showed a significant reduction of clinically documented MRSA infections, from 2.7% to 0.3% (p < 0.05), if their protocol was applied. In addition, the results from the polymerase chain reaction were available an average of 1.5 days before the final culture data. A much higher rate of MRSA colonization was screened on admission than has previously been reported. This may be because of a higher rate of colonization, as MRSA becomes more prevalent in the community or it may be because of more accurate detection of MRSA by polymerase chain reaction. Implementation of an MRSA screening, surveillance, and control policy may be one way of reducing the MRSA infection rate in trauma patients.42 

Management and Treatment

In orthopedic surgery and particularly in the treatment of fractures, postoperative infection is an unfortunate reality. The important questions to be posed are “Is there an infection?” and then “What do I do now?” The challenge is the difficulty in being certain whether an infection exists because we do not have an absolutely reliable method of determining the necessary elements of true postoperative or posttraumatic infection. As previously discussed, the establishment of colonization followed by an opportunistic bacteria, in a compromised host or environment, is necessary to allow an infection to occur. Furthermore, the accuracy and reliability of available diagnostic tests are not 100% and therefore, experience and clinical judgment are vital and could be considered more important than the tests that are currently available. 
As has already been noted, treatment must not only follow basic principles but also must be tailored to the reality of the individual clinical scenario. It would be naive to assume that an inflamed and draining postoperative wound in a polytraumatized patient (B systemic) with significant fracture treatment (B local) that responds to a short course of antibiotics has no chance of recurrence. In such a case, sufficient treatment might have been provided so the balance would tip to favor the host defense mechanism. However, what probably occurred was that the threshold level for infection was exceeded and the body manifested a response in the form of inflammation and drainage. With the use of antibiotic treatment, the bacterial counts were reduced so that the host was able to take over and sequester the infection effectively. Thus, an initial positive response to antibiotic therapy does not necessarily mean that the infection was eradicated. It simply means that it was suppressed and possibly sequestered. Using an oncologic analogy, the infection may have been forced into remission, possibly for an indefinite period, but many of these patients present later with signs of infection in the same limb. Unfortunately, by this time the patient may be older, in poorer health, and less able or willing to tolerate an aggressive ablative procedure, thus lowering the potential for cure. In the long run, early suppression may cause the patient more physical and psychological harm than early aggressive measures to achieve complete eradication. On the other hand, an overaggressiveapproach may require extensive reconstructive efforts that lead to other problems. Thus, in a world seeking clear black and white answers, osteomyelitis usually presents as a shade of gray! 
The principles of osteomyelitis management rely on a multidisciplinary approach that begins with diagnosis and optimization in the form of medicine and radiology and then combines debridement, soft tissue coverage, antimicrobial therapy using orthopedic surgery, microvascular surgery, and infectious disease. This gives the best chance of a cure.37,70 Initially, the infection needs to be diagnosed and the host optimized. This involves treating any comorbidities and optimizing the physiologic condition of the host. Interventions involving nutrition, the use of nicotine, diabetes, vascular disease, and improvement of tissue oxygenation will increase the chances of successful treatment. Secondly, the osteomyelitis needs to be classified and staged. It is then important to identify the organism to determine appropriate antimicrobial treatment. This can be done independently with a bone biopsy or deep culture or, more commonly, it is done at the time of surgery. Identification will also give an idea of the potential virulence of the causative organism, which may influence decisions regarding treatment. We recommend that if the risk of sepsis or amputation is low, then a period of time off all antibiotics may improve bacterial identification. This may be more important in long-standing cases where the usual organisms may have been replaced by other, more exotic species. 
Once the extent of the disease, the nature of the host, and the infecting organism are understood, determination should be made regarding one of several general treatment algorithms. Available treatment options include attempted ablation and cure of the infection, or, in selective cases such as C hosts who are not suitable for surgery, some type of suppressive treatment may be undertaken. Attempted ablation and complete cure have numerous issues and decision-making steps and will often require the oncologic equivalent of a wide resection with clean margins. Although a surgically clean bed with extensive resection is desirable, all efforts should be made to maintain skeletal axial stability where possible. Thus, retention of a well-vascularized, but affected, involucrum or a viable segment of bone adjacent to infection may be preferable to a segmental resection that would add a level of complexity to the treatment regime. If an adequate resection would result in an overextensive reconstruction that is unsuitable for the host’s function or desire, an amputation is the best option and it should not be considered a failure. In some cases of life- or limb-threatening infection, debulking of the infection may be a suitable first step followed by chronic suppression. In these circumstances, identification of the infecting bacteria is required to allow the use of a specific antibiotic. Otherwise, broad-spectrum antibiotics are required. 
We have embraced a collaborative approach with our infectious disease colleagues. Modern antimicrobials have become so numerous and complex that their expert involvement is likely to increase the chances of successful treatment. Increasingly, in many hospitals bone infection mandates an infectious disease consult because of the risk of inadvertently creating resistant pathogens, the efficacy of combined antibiotic protocols, patient safety issues, and the cost of new treatment regimens. However, it is still important that the orthopedist has an understanding of antimicrobial treatment because it is the orthopedist who will initiate the treatment before consulting his or her infectious disease colleagues. We also recommend that orthopedic surgeons recognize that not all infectious disease practices are evidence based and not all specialists have a specific interest and training in bone infections. Therefore, it is vital that the orthopedist initiates an open and collegial partnership with the infectious disease specialists in his or her community to work on behalf of the patient. Both the orthopedic surgeon and the infectious disease physicians should work together to employ a consistent strategy of surgical and chemotherapeutic treatment predicated on the best evidence and logic available. Ziran et al.131 showed that a dedicated team approach can enhance the outcomes of treatment, providing higher cure and successful suppression rates. The subsequent sections in this chapter will briefly review both systemic and local antimicrobial agents as well as discuss the techniques and implants used during treatment. Specific scenarios and algorithms will then be reviewed. 

Antimicrobial Therapy

Prophylaxis

On the basis that prevention is always better than cure, prophylactic antibiotics have an important role in the treatment of closed fractures. The prophylactic use of appropriate antibiotics for closed fractures and elective cases will reduce the incidence of postoperative osteomyelitis. Antibiotic administration is not a substitute for proper aseptic technique, but it is a validated additional measure to reduce postoperative infection. 
The use of prophylactic antibiotics was demonstrated in a Dutch trauma trial that found, in 2,195 cases of closed fracture surgery, a single preoperative dose of ceftriaxone resulted in an infection rate of 3.6% in comparison to a placebo group infection rate of 8.3% (p < 0.001).12 Furthermore, the trial also found that there was a lower incidence of nosocomial urinary tract and respiratory tract infections in the first 30 postoperative days (2.3% vs. 10.2%, p < 0.001). In another retrospective study of 2,847 surgical cases, the timing of antibiotic administration was also found to be an important factor. If the antibiotics were given more than 2 hours before or 3 hours after the incision, there was a six-fold increase in the rate of surgical site infection.21 The current recommendation is that antibiotics should be administered 30 to 60 minutes before the incision is made, except when using vancomycin, where a longer delay permits appropriate infusion rates.12,47,108 For routine uncomplicated closed fracture surgery, prophylaxis should not be administered for greater than 24 hours, and many surgeons believe that only a single dose is necessary. Gillespie and Walenkamp performed a meta-analysis of 8,307 patients undergoing surgical treatment of hip and long bone fractures, to determine whether antibiotic prophylaxis reduced the incidence of wound infection. A total of 22 studies were analyzed. Single doses of antibiotic prophylaxis were found to significantly reduce the incidence of wound infection (relative risk, 0.4; 95% confidence interval, 0.24 to 0.67).47 Controversy exists regarding the appropriate prophylaxis for orthopedic surgical patients in hospitals with high rates of MRSA. Traditional first-generation cephalosporins may not provide adequate coverage, and given the increasing prevalence of MRSA infections in Europe and North America, further studies are needed to understand the risk–benefit ratio of using routine vancomycin as a prophylaxis agent. The disadvantages of potential nephrotoxicity and an increase in the emergence of vancomycin-resistant S. aureus (VRSA) must be weighed against the risk of increased postoperative infection rates. Currently, neither vancomycin nor clindamycin is routinely used except in cases of known PCN or cephalosporin allergy. All institutions should have an infection control committee, including infectious disease specialists, to determine the bacterial spectrum of the institution. An “antibiogram” can then be provided to help determine the best agents to use for prophylactic and therapeutic treatments. In our institution the infection disease specialists recommend the use of vancomycin and rocephin based on our nosocomial bacterial flora. In cases of reported PCN allergy, patients can be given a small test dose of cephalosporin after anesthesia induction to determine if there is any cross-reactivity. 

Open Fractures

Historically, the teaching in open fractures has been to use a first-generation cephalosporin followed by the addition of an aminoglycoside for more contaminated wounds using supplementary PCN if there is any soil contamination. It is perhaps surprising to realize that this recommendation is more than 30 years old and is not supported by any newer, high-level evidence-based studies. This practice was primarily an empirical and theoretical recommendation. Since the incidence of infection is so low that any treatment will also have a small statistical effect size, it may not be possible to undertake a sufficiently powered study to adequately test the success of this antibiotic regimen. A number of studies have examined the role of antibiotics, but the most recent review by the Surgical Infection Society found that current standard antibiotic prophylaxis is based on very limited data.55 
Another question that remains unanswered concerns the true requirement for aminoglycosides at the time of injury. Given that the initial organism is often a Staphylococcus but that the eventual infective organism is a resistant gram-negative organism, it begs the question of whether early aminoglycoside administration, which is often given in adequate doses, will promote the development of a resistant organism. In two studies, a cephalosporin alone performed as well as the combination of a cephalosporin and PCN or the combination of a cephalosporin and an aminoglycoside.92 Another study examining the use of broad-spectrum antibiotics proposed that their use could result in the development of resistant bacteria. 
Analysis of the US military experience with high-energy open fractures has shown that there is sufficient level I data to support the use of a cephalosporin but that the use of aminoglycosides, even for grade III open fractures, may be deleterious. These recommendations are based on timely and adequate surgical debridement. If there is a delay to treatment whereby bacterial colonization may have begun and matured or if the wound is such that gram-negative bacteria or anaerobic conditions exist, then supplementation with appropriate antibiotics, in addition to a more aggressive initial debridement, may be useful. Because there is little scientific evidence about the subject, much current surgical practice is anecdotal. The authors believe that the initial debridement is the most important principle of open fracture treatment as well as in the management of acute or chronic infection. Minimalist approaches to the removal of devitalized tissue, in the hopes of preventing extensive later reconstructive surgery, are usually doomed to failure. By the surgeon taking less initially, the patient is often condemned to lose more later because of ongoing infection and diffuse tissue destruction. 
The duration of antibiotic use in open fractures has also been poorly studied, but the current recommendation is to use antibiotics for 1 to 3 days following wound closure or coverage with ongoing treatment based on a reassessment of the injury zone. However, the current practice of continuing the use of antibiotics until definitive wound closure has occurred has no scientific basis. In fact, the literature suggests that the long duration of empirical or prophylactic antibiotic use may breed resistant organisms. The current recommendation is to use antibiotics for an extended period only if this is supported by the condition of the wound which will show signs of infection.83 The author’s institutions summarized the available literature and concluded that open fractures should be treated with antibiotics for 24 hours following definitive wound closure. These are also the recommendations being developed in new guidelines by the U.S. Centers for Disease Control and Prevention (CDC). Recently, a journal supplement focusing on military injuries has examined and summarized the current thinking on extremity infection in war time injury.83,84 A recent study evaluated the timing of wound closure based on cultures. Antibiotics were continued based on ongoing positive cultures and wounds were only closed after negative culture results. Antibiotics were resumed, based on clinical evaluation, if cultures were positive after wound closure. 

Established Infection

As the duration of antibiotic administration for chronic infections may be prolonged the antibiotics that are used to treat the infection should ideally be nontoxic, convenient to administer, affordable and based on the in vitro susceptibilities of the organisms. All antibiotics have potential adverse effects and complications and an infection disease specialist should be involved in the treatment regime. Table 26-5 lists treatment regimes for a number of different organisms that commonly cause osteomyelitis. Any antibiotic that is used should have reliable bone penetration, and the serum and bone concentrations for a number of antibiotics are shown in Table 26-6. There is no general consensus about the duration of antibiotic administration for osteomyelitis with some researchers suggesting 2 weeks and others considerably longer. Short-term therapy may be used in otherwise healthy patients who have healthy tissue and have had a total debridement. Longer-term therapy will usually be used in patients with virulent or long-standing infections in whom the initial debridement will be followed at a later date by staged reconstruction. It is also used if there are retained implants. 
 
Table 26-5
Common Bacteria-Specific Antibiotic Regimens
View Large
Table 26-5
Common Bacteria-Specific Antibiotic Regimens
Organism First-Line Antibiotic(s) Alternative Antibiotic(s)
Staphylococcus aureus or coagulase-negative staphylococci (methicillin-sensitive), MSSA Oxacillin 2 g IV q6h
Clindamycin 600 mg IV q8h
First-generation cephalosporin, vancomycin, daptomycin, tigecycline
S. aureus or coagulase-negative staphylococci (methicillin-resistant), MRSA Vancomycin 1 g IV q12h ± Rifampin 300 mg PO BID Linezolid, trimethoprim/sulfamethoxazole or minocycline + rifampin, daptomycin, tigecycline
Penicillin-sensitive Streptococcus pneumoniae, varied streptococci (groups A and B hemolytic organisms) Penicillin G, 4 million units IV q6h
Ceftriaxone 2 g IV QD
Cefazolin 1 g IV q8h
Clindamycin, erythromycin, vancomycin
Intermediate penicillin-resistant S. pneumoniae Ceftriaxone 2 g IV q24h Erythromycin, clindamycin, or fluoroquinolone
Penicillin-resistant S. pneumoniae Vancomycin 1 g IV q12h Fluoroquinolone
Enterococcus spp. Penicillin G, 4 million units IV q6h
Ampicillin 2 g IV q6h + Gentamicin 3–5 mg/kg/day
Vancomycin 1 g IV q12h
Ampicillin–sulbactam, linezolid, daptomycin, tigecycline + gentamicin
Pseudomonas spp., Serratia spp., or Enterobacter spp. Cefepime 2 g IV q12h ± Fluoroquinolone (Table 26-7)
Meropenem 1 g IV q8h
Fluoroquinolone, ertapenem
Enteric gram-negative rods Ceftriaxone 2 g IV q24h
Fluoroquinolone (see later)
Third-generation cephalosporin
Anaerobes Clindamycin 600 mg IV q8h
Metronidazole 500 mg PO q4h
For gram-negative anaerobes: amoxicillin–clavulanate or metronidazole
Mixed aerobic and anaerobic organisms Amoxicillin–clavulanate 3 g IV q6h Ertapenem
 

Fluoroquinolones: ciprofloxacin 750 mg PO BID, levofloxacin 500 mg PO QD, moxifloxacin 400 mg PO QD.

 

Note that use of fluoroquinolones has been associated with altered bone healing in animal models and increased risk of tendon rupture in humans.

 

Note that many antibiotics may result in development of severe colitis.

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Table 26-6
Serum and Bone Concentrations After Antibiotic Administration
Antibiotic Serum Bone % Serum
Clindamycin (7 mg/kg) 2.1 ± 0.6 1.9 ± 1.9 98.3
Vancomycin (30 mg/kg) 36.4 ± 4.6 5.3 ± 0.8 14.5
Nafcillin (40 mg/kg) 21.8 ± 4.6 2.1 ± 0.3 9.6
Moxalactam (40 mg/kg) 65.2 ± 5.2 6.2 ± 0.7 9.5
Tobramycin (5 mg/kg) 14.3 ± 1.3 1.3 ± 0.1 9.1
Cefazolin (15 mg/kg) 7.2 ± 2.6 4.1 ± 0.7 6.1
Cefazolin (5 mg/kg) 45.6 ± 3.2 2.6 ± 0.2 5.7
Cephalothin (40 mg/kg) 34.8 ± 2.8 1.3 ± 0.2 3.7
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If the patient requires grafting or reconstruction after a successful debridement, antibiotics will often be administered for 6 to 8 weeks followed by a period of antibiotics with monitoring of the CRP and ESR. A rebiopsy may also be undertaken. If there are no ongoing indicators of infection, reconstruction can usually be performed without additional long-term antibiotic treatment. There are a number of factors which should be considered when considering long-term antibiotics. There are reports of immunosuppression, allergic reaction, poor tolerance, poor compliance, and financial hardship that must also be considered when deciding on long-term antibiotic administration. To increase patient compliance the antibiotics that are used should be the least toxic and least expensive and preferably require administration once or twice daily. The oral antibiotics with excellent bioavailability are listed in Table 26-7. These antibiotics may be substituted for intravenous agents whenever possible, provided that the organism is susceptible and the bone penetration is adequate. 
Table 26-7
Selected Oral Antimicrobial Agents with Excellent Oral Bioavailability Commonly Used to Treat Osteomyelitis
Antimicrobial Agents
Fluoroquinolones Ciprofloxacin 750 mg q12h
Levofloxacin 500 mg q12h
Moxifloxacin 400 mg q12h
Mixed Metronidazole 500 mg q8h
Linezolid 600 mg q12h
Rifampin 300 mg q12h (not to be used alone)
Trimethoprim/sulfamethoxazole 1 DS QD
Minocycline–doxycycline 100 mg q12h
Azoles (antifungal) Fluconazole 400 mg q24h
Itraconazole 200 mg q12h
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Because of increased incidences of vancomycin-resistant Enterococcus, especially in intensive care units, and VRSA, vancomycin should be used only if there is a high institutional incidence of MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). A single dose of vancomycin administered before surgery and followed by two or three doses postoperatively should provide adequate perioperative prophylaxis in high-risk cases. Vancomycin should only be used with type I hypersensitivity to cephalosporins that includes patients with urticaria, laryngeal edema, and bronchospasm, with or without cardiovascular shock. Clindamycin is considered the substitute of choice when cephalosporins are contraindicated. 
There are also little data with regard to the use and duration of antibiotics in established infection. The most common practice is to begin with a 2- to 6-week course of a species-specific, bioavailable agent.63 Such an agent may be used until adequate revascularization occurs. With the advent of many new and expensive oral agents, it may be possible to reduce the morbidity associated with intravenous use with an early step-down program converting to an oral agent. Obviously, this regimen may be less successful with resistant organisms. Thus, to date there have been few recommendations for the duration of antibiotics in established osteomyelitis. 
A common clinical scenario is the partially treated infection. Patients who may have been suppressed but incompletely treated may present with an acutely inflamed, limb-threatening condition. Our approach has been to continue the use of antibiotics during the diagnostic and staging period when the necessary tests are undertaken and the host is optimized. However, we believe that as long as there are no signs of impending sepsis or limb loss, it is worthwhile stopping antibiotic treatment 1 to 2 weeks before surgical intervention so that more precise and reliable bacterial identification is possible. Begin an empirical course of antibiotics intraoperatively after all the cultures have been taken and continue until the culture results are available. In chronic cases, we will cover both gram-negative and MRSA and collaborate with our infectious disease colleagues regarding final antibiotic selection and management. 

Irrigation Solutions

The original use of pulsatile irrigation was based on early studies of infections, which recommended that colonized bacteria are adherent to tissue and needed to be moved from the surface. Although such mechanical cleansing may work, mature colonies of bacteria are not easily eradicated with this method. Furthermore, there is evidence that the velocity of the fluid stream may be deleterious to both bone and soft tissue cells.3,8,13,53,113 So while high-pressure flow has been shown to damage bone or push bacteria even deeper into the wound, low-pressure lavage appears to be adequate without having the tissue-damaging effects.8,13,53 
Irrigation with saline alone has been shown in animal studies to reduce colony counts by about 50% in contaminated wounds.7 However, conflicting studies have shown no beneficial effect of the use of saline.15,23 In one study, tap water was compared with sterile saline irrigation and no difference was found in infection rates.80 The effect of adding bacteriocidal agents to irrigation solutions to aid with both bacterial removal and destruction has also been studied in an adherent staphylococci model.8 These studies have shown that although solutions such as Betadine and hydrogen peroxide are effective in eliminating bacteria, they are also toxic to osteoblasts. Also, the addition of antibiotics to irrigation solutions has had mixed results, and overall it appears to have little benefit but there is a significant increase in cost. Their use as an adjunct to irrigation solutions is questionable at best.4,34,94 One study, using a goat model, found that the use of certain bacteriocidal agents in irrigating solutions resulted in a rebound bacterial count 24 to 48 hours after irrigation.89 Another study used gentamicin placed into the wound bed together with a systemic cephalosporin in an animal model. They found significantly lower bacterial counts.16 Our institution has been using clorpactin (WCS-90, USA Guardian Laboratories, Hauppauge, NY) solution in their irrigation for decades. It is typically used as a topical agent for complicated burn wounds and is similar to sodium hypochlorite. We currently use a combination of clorpactin and gentamicin in our irrigating solutions because it is inexpensive and has low morbidity together with reasonable supportive evidence of efficacy. 
Given the minimal effects of antibiotics in irrigation fluids, detergent-type compounds or surfactant solutions have been recently investigated as a way of disrupting the hydrophobic or electrostatic forces that drive the initial stages of bacterial surface adhesion. A sequential surfactant–irrigation protocol was developed and shown to be effective in polymicrobial wounds associated with an established infection.5,35,82 Detergents, or soaps, have been shown to be the only irrigation solutions that remove additional bacteria beyond the effect of mechanical irrigation alone.8 Moreover, soap solutions have been found to have minimal effects on bone formation and osteoblast numbers in vitro.7 The proposed mechanism of their effect is based on the formation of micelles that overcome the strength of the interaction between the organisms and the bone. Castile soap has recently been reported to be useful in this situation.5,82 

Antibiotic Depot Devices and Techniques

The concept of local antibiotic therapy in the form of antibiotics impregnated in bone cement to reduce infected arthroplasties was introduced in the 1970s. As a result of the success of this work, interest developed in using antibiotic-impregnated bone cement as treatment for osteomyelitis. Keating et al.60 reported a 4% infection rate in 53 open tibial fractures with tobramycin-impregnated beads. Ostermann et al.88 reported a significant difference in infection rates with grade IIIB fractures treated with aminoglycoside beads together with parenteral antibiotics compared with patients who only received parenteral antibiotics. They reported a 6.9% infection rate in 112 patients with combined therapy compared with a 40.7% infection rate in 27 patients who only had parenteral antibiotics. The use of antibiotic depots allows for high local concentrations of antibiotic with little systemic absorption. Antibiotic release is biphasic with most occurring during the first few days to weeks after implantation. However, elution of the antibiotic persists for several weeks. Occasionally, antibiotics can be recovered after several years, but because the elution is based on a diffusion gradient, only the outer 1 cm or so of large-volume depots will elute antibiotic. The core of such large-volume depots will often contain antibiotic but it will not be useful.62,111 
The key issue of the polymethyl methacrylate (PMMA) antibiotic depot is the need for a heat-stable antibiotic agent because during the cement hardening process, the exothermic reaction can render heat-labile antibiotics ineffective. Some of the antibiotics that have been tried with PMMA include clindamycin, which elutes well but is not available as a pharmaceutical grade power. Fluoroquinolones have been reported to have suitable elution, but clinical reports of their success are lacking.33 Erythromycin was used in some earlier studies, but a subsequent study showed inadequate elution of erythromycin from Palacos cement. Macrolides and azalides are unavailable, and tetracycline and polymyxin E (Colistin) fail to elute from the Palacos cement in clinically useful quantities. Another issue with PMMA depot systems is that they require removal. If they are left for a prolonged period, the PMMA spaces can become encased in scar and may be difficult to remove. After antibiotics have eluted from the outer surface of the cement mass, the surface is rendered unprotected and may provide a suitable surface for secondary colonization. When used acutely for open fractures or for a short period, removal is not generally problematic and may even be undertaken percutaneously. There are entire issues of Clinical Orthopaedics and Related Research (numbers 295 and 420) dedicated to the use of PMMA antibiotic depot methods to which the reader is referred for more in-depth information.1,2 The authors’ formulation for PMMA antibiotic-laden beads uses vancomycin and tobramycin. Although up to 4 g of vancomycin and 4.8 g of tobramycin can be mixed per 40-g bag of cement, the cement may become difficult to manage. Other PMMA formulations such as Cranioplast do not tolerate even small amounts of antibiotic powder. For routine use, we place between 1 and 2 g of vancomycin and 1.2 to 2.4 g of tobramycin per bag. Depending on the clinical situation, we have developed a method to create three forms of antibiotic beads. We first cut a length of 18-gauge steel wire and loop one end. As the bowl becomes doughy, we roll multiple cement balls of about 1 to 2 cm in diameter. The wire is then moistened with water and the bead is allowed to slide and drop on the wire. The adherent cement is cleaned off the wire to allow subsequent beads to slide down. After the beads are placed, they can be left to cure as balls or they may be checked into oblong sausage-shaped beads by rolling them like dough. Alternatively, they can be shaped into discs by simply pressing each bead flat on the wire. We prefer the use of discs because they fit better between tissue planes and are less likely to have local compressive effects on the tissues (Fig. 26-13). 
Figure 26-13
The manufacture of antibiotic bone cement beads and discs.
 
A: Antibiotic balls placed on a stainless steel wire to form beads. One ball has been flattened to form a disc. B: The final appearance of antibiotic discs. They produce less local tissue pressure and ischemia than antibiotic balls.
A: Antibiotic balls placed on a stainless steel wire to form beads. One ball has been flattened to form a disc. B: The final appearance of antibiotic discs. They produce less local tissue pressure and ischemia than antibiotic balls.
View Original | Slide (.ppt)
Figure 26-13
The manufacture of antibiotic bone cement beads and discs.
A: Antibiotic balls placed on a stainless steel wire to form beads. One ball has been flattened to form a disc. B: The final appearance of antibiotic discs. They produce less local tissue pressure and ischemia than antibiotic balls.
A: Antibiotic balls placed on a stainless steel wire to form beads. One ball has been flattened to form a disc. B: The final appearance of antibiotic discs. They produce less local tissue pressure and ischemia than antibiotic balls.
View Original | Slide (.ppt)
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Recently, intramedullary antibiotic cement rods have been used. These are fashioned by using a large 36 French thoracotomy tube and placing an 18- to 20-gauge wire inside. After the tube has been cut to discard the ventholes, bone wax or a Kelly clamp can be used to obstruct the thin end. The antibiotic–cement mixture is then injected into the tube in a liquid state. Once the cement cures, the thoracostomy tube is cut off with a scalpel and the rod can then be used. It is important to ensure that both canal diameter and rod length have been measured (Fig. 26-14). 
Figure 26-14
The manufacture of an antibiotic nail.
 
Several methods have been advocated. A: In this example a stainless steel wire is placed within a thoracotomy tube and the tube is filled with antibiotic impregnated cement. It is then cut to allow removal of the rod. B: This shows the antibiotic-impregnated rod. An alternative is to use a threaded bone transport rod. This will enhance strength but may reduce the size and strength of the cement mantle.
Several methods have been advocated. A: In this example a stainless steel wire is placed within a thoracotomy tube and the tube is filled with antibiotic impregnated cement. It is then cut to allow removal of the rod. B: This shows the antibiotic-impregnated rod. An alternative is to use a threaded bone transport rod. This will enhance strength but may reduce the size and strength of the cement mantle.
View Original | Slide (.ppt)
Figure 26-14
The manufacture of an antibiotic nail.
Several methods have been advocated. A: In this example a stainless steel wire is placed within a thoracotomy tube and the tube is filled with antibiotic impregnated cement. It is then cut to allow removal of the rod. B: This shows the antibiotic-impregnated rod. An alternative is to use a threaded bone transport rod. This will enhance strength but may reduce the size and strength of the cement mantle.
Several methods have been advocated. A: In this example a stainless steel wire is placed within a thoracotomy tube and the tube is filled with antibiotic impregnated cement. It is then cut to allow removal of the rod. B: This shows the antibiotic-impregnated rod. An alternative is to use a threaded bone transport rod. This will enhance strength but may reduce the size and strength of the cement mantle.
View Original | Slide (.ppt)
X
Most of the antibiotic cement used in the United States has been off-label use by the surgeon, and despite encouraging results from several studies, their approval by the U.S. Food and Drug Administration has been discouragingly slow. There are a number of commercial antibiotic-impregnated PMMA cements becoming available in the United States, and of course they have been available for some time in other parts of the world. We believe that the use of an aminoglycoside in antibiotic-impregnated cement does not provide the versatility that we need because vancomycin should be considered when there is a chance of resistant staphylococcal organisms. Thus, commercially produced antibiotic-laden cement may best be suited as prophylaxis during cemented arthroplasty. 
There are also newer types of material available for local delivery of antibiotics that are resorbable and do not require removal. Surgical grade calcium sulfate has been used recently, and its use is reported in both open fractures and infections.74 Although calcium sulfate products have been promoted as a bone graft substitute, there are little data in human fractures and infections demonstrating the efficacy of this dual function of depot and graft. Calcium sulfates and carbonate will absorb or dissolve independently of bone formation, whereas calcium phosphates tend to be replaced very slowly with bone. Furthermore, large volumes of calcium sulfate can cause an osmotic effect that results in fluid accumulation and the potential for seroma formation and wound drainage. When mixed with fluid and blood, the calcium drainage looks like bloody pus and may prompt extra surgical treatments resulting in unacceptable complication rates.11,132 In one study, the use of a calcium sulfate-demineralized bone matrix (DBM) mixture (Allomatrix; Wright Medical, Memphis, TN) resulted in an unacceptably high rate of drainage, infection, and failure. We have heard of numerous anecdotal reports concerning the drainage problem of calcium sulfate and we do not recommend its use as a bone graft substitute. However, we have found it useful as an antibiotic depot. To minimize the drainage problem, we do not recommend placing a large amount of calcium sulfate beads into a cavity, but if this is unavoidable, a multiple-level water-tight closure is essential. We have not found any problems with drainage when the beads are interspersed in small spaces and tissue planes. Another feature to note is that the addition of tobramycin to calcium sulfate greatly prolongs the setting time, which may be 30 to 45 minutes. Vancomycin greatly shortens the setting time, which may be as fast as 2 minutes, and for this reason the agent may be impractical. We routinely use both vancomycin and tobramycin for high-risk infections and find that the effect of tobramycin dominates the settling profile. Thus, despite a seemingly novel concept and marketing claims, such products should be used with caution and experience. 
The use of impregnated hydroxyapatite ceramic beads may simulate a bone graft by serving as an osteoconductive matrix, but they are resorbed slowly, and after elution may behave as a foreign body with potential reinfection as may occur with PMMA beads. Gentamicin-impregnated polylactide–polyglycolide copolymer implants are biodegradable and may not need removal once they have been implanted. However, there is little clinical experience, and it is possible that they elicit an inflammatory response that may mimic acute infection. 

Debridement Techniques

If surgical treatment is chosen, the hallmark of treatment is debridement. All nonviable and inert structures should be debrided to remove infected material and debris without destabilizing the bony structure. The goal is to convert a necrotic, hypoxic, infected wound to a viable wound. The critical judgment for the surgeon occurs when there is a potentially infected bone, which might be partially vascularized, which is needed to maintain the structural stability of the bone. Sinus tracts that are present for longer than 1 year should be excised and sent for pathologic examination to rule out an occult carcinoma.104 Soft tissue retraction should be minimal and flaps should not be created. There is a balance between leaving behind infection, which may result in recurrence, and resection and subsequent destabilization, which might necessitate extensive surgical reconstruction with its associated risks. The risk–benefit ratio must be evaluated in each case and should form the basis of thorough informed consent. 
Meticulous debridement is one of the most important initial steps in the treatment of infected bone and soft tissue. The limits of debridement have classically been determined by the “paprika sign,” which is characterized by punctuate cortical or cancellous bleeding (Fig. 26-15). Efforts should be made to limit any periosteal stripping that may further devitalize the bone. Reactive new bone surrounding an area of chronic inflammation is living and sometimes does not require debridement.18 Any sequestrated dead bone needs to be identified and removed, whereas live bone may be preserved. Rapid debridement can be achieved with a high-speed burr but used with continuous irrigation to limit thermal necrosis. Laser Doppler flowmetry may facilitate accurate assessment of the microvascular status of bone, thereby identifying it for removal.36 However, we have found this technique to have little benefit compared with visual inspection. Laser Doppler flowmetry is the only nondestructive in vivo method of blood flow determination that provides instantaneous determination of perfusion. 
Figure 26-15
The appearance of bone at debridement.
 
Note that the living bone has a pinkish hue and a petechial appearance indicating vascularity. The surrounding bone is involucrum and is also vascular. Resection of the involucrum should be at the judgment of the surgeon. The dead bone is clearly avascular and requires resection.
Note that the living bone has a pinkish hue and a petechial appearance indicating vascularity. The surrounding bone is involucrum and is also vascular. Resection of the involucrum should be at the judgment of the surgeon. The dead bone is clearly avascular and requires resection.
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Figure 26-15
The appearance of bone at debridement.
Note that the living bone has a pinkish hue and a petechial appearance indicating vascularity. The surrounding bone is involucrum and is also vascular. Resection of the involucrum should be at the judgment of the surgeon. The dead bone is clearly avascular and requires resection.
Note that the living bone has a pinkish hue and a petechial appearance indicating vascularity. The surrounding bone is involucrum and is also vascular. Resection of the involucrum should be at the judgment of the surgeon. The dead bone is clearly avascular and requires resection.
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When the medullary canal is infected, intramedullary reaming is an effective method of debridement that preserves cortical stability.24 In general, one should overream the medullary canal by 2 mm. Excessive reaming may cause cortical necrosis and exacerbate infection by increasing the surface area of dead bone. Lavage can be performed from the reaming entry portal with the canal irrigator tips used in arthroplasty, with egress being provided through a vent or previous locking screw holes (Fig. 26-16). Dull reamers and the generation of heat should be avoided to prevent further cortical necrosis. 
The distal screw holes are connected and opened to create an efflux portal.
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Figure 26-16
Intraoperative photograph of medullary canal lavage after removal of an intramedullary rod and the use of a medullary canal irrigator.
The distal screw holes are connected and opened to create an efflux portal.
The distal screw holes are connected and opened to create an efflux portal.
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The recent use of the reamer–irrigator–aspirator (RIA) system72,97 provides high-speed reaming debridement combined with continuous irrigation and aspiration of the medullary contents. Numerous centers have advocated its use in the debridement of infected long bones. We routinely use this technique in intramedullary canal debridement. Its advantages include vigorous cleaning of the canal and a decrease in embolization of marrow contents, and potentially bacteria, into the systemic circulation. Disadvantages include increased cost and a learning curve regarding matching the size of the reamer to the canal size. Choosing too small a reamer provides inadequate debridement and too large may cause a shaft fracture. Sizing should be performed preoperatively with digital radiography and then rechecked intraoperatively with fluoroscopy and an intraoperative measuring guide. 
Intramedullary reaming of the medullary canal as a debridement technique has shown favorable results in the treatment of medullary osteomyelitis. In a cohort of 32 patients who had had an average of 3.2 surgical operations for osteomyelitis, Pape et al.91 found that reaming of the medullary canal was successful in that 84% of patients were able to return to their previous profession and 97% were pain-free. Evidence for the treatment of an infected intramedullary nail has been largely derived from observational data. Pommer et al.96 found that reaming of an infected intramedullary canal resulted in eradication of infection in all patients when the infection occurred after primary intramedullary nailing compared with 62% of those with multiple operations before reaming and nailing. Ochsner et al. treated 25 patients with posttraumatic osteomyelitis, of whom 22, who were treated with intramedullary reaming, were followed for at least 6 months. Twenty-one of the twenty-two patients were free of any recurrent infection after an average period of 26 months. In a more recent study Ochsner et al. documented 40 patients with chronic osteomyelitis who were treated with intramedullary reaming. Only four patients had a recurrent infection.87 If the medullary infection is too proximal or distal for a tight reamer fit, saucerization must be undertaken with the trough being created to debride the canal directly. Biomechanically, the most desirable shape for the trough is an oval, with this shape resulting in minimal diminution of the bone’s torsional strength. If segmental resection is undertaken or there is more than 30% loss of circumferential cortical contact, stabilization is required. 

Considerations in the Geriatric Patient

The geriatric patient population is not only increasing because of the increased birth rate after World War II, but also because advances in healthcare have resulted in increased longevity. Unfortunately, like most physical processes and materials, wear and tear and aging have irreversible consequences that can only mitigated or delayed. Thus the older patient will experience deterioration in bodily function that affects orthopedic treatment, whether it is for acute trauma, reconstruction, or infection. 
The treatment principles are the same as for any age group, namely diagnosis, staging, and attempted eradication. In the geriatric population, several additional considerations must be taken into account. First is their physiologic ability to tolerate the extent of reconstruction that is necessary. Most of the elderly will, by definition, be B hosts, and many will be considered C hosts because of multiple comorbidities. Thus, a stage IV, B-systemic/local osteomyelitis of the distal tibia requiring a 6-cm resection and free tissue transfer, followed by bone transport, may not be feasible in such a patient. Instead, this patient should be considered for a limited resection and chronic suppressive therapy or an amputation, despite the cardiopulmonary drawbacks. The tenet that optimization of the host is needed is even more important in this age group. Not only should nutritional and local tissue conditions be optimized, but underlying physiologic disorders should be addressed to minimize the risk of perioperative complications. 
Secondly, the expectations and demands of the patient must be considered. Most of these patients will be retired and have limited demands, and therefore may not require what a 30-year old-construction worker or mother of three requires. Once again, the consideration of limited nonablative treatment that allows a comfortable existence with a “treated” infection, with or without chronic suppressive therapy, becomes much more attractive in this population. In some patients, an appropriately done debridement with the use of depots and stabilization, along with suppressive antibiotics, may be sufficient for their lower demands, especially if they have concomitant comorbidities that make repeated surgical interventions risky (Fig. 26-17). 
Figure 26-17
The case of a 75-year-old female with previous plating and intramedullary nailing.
 
She had developed intramedullary infection and nonunion. A: Her nail was removed and intramedullary irrigation was performed using a reamer–irrigator–aspirator. B: She then had an antibiotic-impregnated PMMA rod, with a metal core, placed into the intramedullary canal. C: She developed a small area of posterior bridging, which may have been stimulated by the reaming and debridement, but she had not completely healed by 9 months. She had no evidence of infection after discontinuation of oral antibiotics. D, E: She had little or no pain despite a CT scan which showed no evidence of healing and was happy wearing a cam walker when outside. Further attempts to gain union would have put the patient through several surgical procedures including the need for soft tissue cover. In her case, her expectations and demands warranted a less aggressive approach.
She had developed intramedullary infection and nonunion. A: Her nail was removed and intramedullary irrigation was performed using a reamer–irrigator–aspirator. B: She then had an antibiotic-impregnated PMMA rod, with a metal core, placed into the intramedullary canal. C: She developed a small area of posterior bridging, which may have been stimulated by the reaming and debridement, but she had not completely healed by 9 months. She had no evidence of infection after discontinuation of oral antibiotics. D, E: She had little or no pain despite a CT scan which showed no evidence of healing and was happy wearing a cam walker when outside. Further attempts to gain union would have put the patient through several surgical procedures including the need for soft tissue cover. In her case, her expectations and demands warranted a less aggressive approach.
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Figure 26-17
The case of a 75-year-old female with previous plating and intramedullary nailing.
She had developed intramedullary infection and nonunion. A: Her nail was removed and intramedullary irrigation was performed using a reamer–irrigator–aspirator. B: She then had an antibiotic-impregnated PMMA rod, with a metal core, placed into the intramedullary canal. C: She developed a small area of posterior bridging, which may have been stimulated by the reaming and debridement, but she had not completely healed by 9 months. She had no evidence of infection after discontinuation of oral antibiotics. D, E: She had little or no pain despite a CT scan which showed no evidence of healing and was happy wearing a cam walker when outside. Further attempts to gain union would have put the patient through several surgical procedures including the need for soft tissue cover. In her case, her expectations and demands warranted a less aggressive approach.
She had developed intramedullary infection and nonunion. A: Her nail was removed and intramedullary irrigation was performed using a reamer–irrigator–aspirator. B: She then had an antibiotic-impregnated PMMA rod, with a metal core, placed into the intramedullary canal. C: She developed a small area of posterior bridging, which may have been stimulated by the reaming and debridement, but she had not completely healed by 9 months. She had no evidence of infection after discontinuation of oral antibiotics. D, E: She had little or no pain despite a CT scan which showed no evidence of healing and was happy wearing a cam walker when outside. Further attempts to gain union would have put the patient through several surgical procedures including the need for soft tissue cover. In her case, her expectations and demands warranted a less aggressive approach.
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The option of arthroplasty must also be considered. While arthroplasty is contraindicated in active infection a staged treatment consisting of an aggressive debridement and antibiotic suppression (local and systemic) may be a reasonable option in such patients. The use of an antibiotic cement spacer and suppressive antibiotic therapy may be so successful that the patients may be happy and not want to undergo subsequent treatment (Figs. 26-18 and 26-19). 
Figure 26-18
The case of an 80-year-old female who had undergone several attempts at reconstruction of a periprosthetic fracture.
 
A: She presented with distally based infection that involved the plate, allograft, and distal aspect of the stem. She was a B-systemic/local host and extensive reconstruction efforts were not feasible. The plan was to perform a staged reconstruction using an arthroplasty. B: Intraoperatively, the infection was localized mostly to the middle part of the femur. The cup was well fixed and did not appear to have any involvement in the infection. C, D: A custom-made, weight-bearing antibiotic spacer was created using a coated tibial nail. E: After a 6-week course of IV antibiotics, during which time she was allowed to weight bear for transfers, she returned for reconstruction with a partial femoral replacement. Because of the proximity of the infection and potential for colonization, as well as her host status, she was maintained on suppressive oral antibiotics for an extended period of time as recommended by a musculoskeletal infectious disease specialist.
A: She presented with distally based infection that involved the plate, allograft, and distal aspect of the stem. She was a B-systemic/local host and extensive reconstruction efforts were not feasible. The plan was to perform a staged reconstruction using an arthroplasty. B: Intraoperatively, the infection was localized mostly to the middle part of the femur. The cup was well fixed and did not appear to have any involvement in the infection. C, D: A custom-made, weight-bearing antibiotic spacer was created using a coated tibial nail. E: After a 6-week course of IV antibiotics, during which time she was allowed to weight bear for transfers, she returned for reconstruction with a partial femoral replacement. Because of the proximity of the infection and potential for colonization, as well as her host status, she was maintained on suppressive oral antibiotics for an extended period of time as recommended by a musculoskeletal infectious disease specialist.
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Figure 26-18
The case of an 80-year-old female who had undergone several attempts at reconstruction of a periprosthetic fracture.
A: She presented with distally based infection that involved the plate, allograft, and distal aspect of the stem. She was a B-systemic/local host and extensive reconstruction efforts were not feasible. The plan was to perform a staged reconstruction using an arthroplasty. B: Intraoperatively, the infection was localized mostly to the middle part of the femur. The cup was well fixed and did not appear to have any involvement in the infection. C, D: A custom-made, weight-bearing antibiotic spacer was created using a coated tibial nail. E: After a 6-week course of IV antibiotics, during which time she was allowed to weight bear for transfers, she returned for reconstruction with a partial femoral replacement. Because of the proximity of the infection and potential for colonization, as well as her host status, she was maintained on suppressive oral antibiotics for an extended period of time as recommended by a musculoskeletal infectious disease specialist.
A: She presented with distally based infection that involved the plate, allograft, and distal aspect of the stem. She was a B-systemic/local host and extensive reconstruction efforts were not feasible. The plan was to perform a staged reconstruction using an arthroplasty. B: Intraoperatively, the infection was localized mostly to the middle part of the femur. The cup was well fixed and did not appear to have any involvement in the infection. C, D: A custom-made, weight-bearing antibiotic spacer was created using a coated tibial nail. E: After a 6-week course of IV antibiotics, during which time she was allowed to weight bear for transfers, she returned for reconstruction with a partial femoral replacement. Because of the proximity of the infection and potential for colonization, as well as her host status, she was maintained on suppressive oral antibiotics for an extended period of time as recommended by a musculoskeletal infectious disease specialist.
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Figure 26-19
The case of a 78-year-old female who had multiple comorbidities and was nearly a C host.
 
A: She had undergone an attempted reconstruction of a periprosthetic fracture in a rural community hospital. Her workup indicated a high likelihood of infection in the diaphyseal region without involvement of the hip area. B: She underwent a staged reconstruction that maintained the femoral head and neck using a custom-made antibiotic-coated prosthesis. After a 6-week course of antibiotics, during which she was ambulatory with assistance, she was scheduled for reconstruction with a total hip arthroplasty and partial femoral replacement. She felt “so good” that she refused any further treatment and she died prior to reconstruction.
A: She had undergone an attempted reconstruction of a periprosthetic fracture in a rural community hospital. Her workup indicated a high likelihood of infection in the diaphyseal region without involvement of the hip area. B: She underwent a staged reconstruction that maintained the femoral head and neck using a custom-made antibiotic-coated prosthesis. After a 6-week course of antibiotics, during which she was ambulatory with assistance, she was scheduled for reconstruction with a total hip arthroplasty and partial femoral replacement. She felt “so good” that she refused any further treatment and she died prior to reconstruction.
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Figure 26-19
The case of a 78-year-old female who had multiple comorbidities and was nearly a C host.
A: She had undergone an attempted reconstruction of a periprosthetic fracture in a rural community hospital. Her workup indicated a high likelihood of infection in the diaphyseal region without involvement of the hip area. B: She underwent a staged reconstruction that maintained the femoral head and neck using a custom-made antibiotic-coated prosthesis. After a 6-week course of antibiotics, during which she was ambulatory with assistance, she was scheduled for reconstruction with a total hip arthroplasty and partial femoral replacement. She felt “so good” that she refused any further treatment and she died prior to reconstruction.
A: She had undergone an attempted reconstruction of a periprosthetic fracture in a rural community hospital. Her workup indicated a high likelihood of infection in the diaphyseal region without involvement of the hip area. B: She underwent a staged reconstruction that maintained the femoral head and neck using a custom-made antibiotic-coated prosthesis. After a 6-week course of antibiotics, during which she was ambulatory with assistance, she was scheduled for reconstruction with a total hip arthroplasty and partial femoral replacement. She felt “so good” that she refused any further treatment and she died prior to reconstruction.
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Author’s Preferred Methods

 
 
Initial Evaluation
 

The authors assume that any patient with a history of surgical fracture treatment, subsequent drainage, wound dehiscence, antibiotic treatment, or unplanned surgery may potentially have osteomyelitis. Many of these patients present with a paucity of medical records and other details, and often their own recollection of events is poor. Therefore, we presume infection until we have strong evidence to the contrary, particularly if symptoms occur in conjunction with fracture nonunion.

 

The host is classified first and efforts are made to optimize the host status. Improving nutrition and tissue oxygenation is important before embarking on surgical treatment. Occasionally, hyperbaric oxygen is helpful if it is available and can be tolerated by the patient. Ideally, the patient should stop smoking, but this is generally difficult to accomplish. However, we encourage patients to limit nicotine use because it is thought that nicotine causes local microvascular effects. Therefore, nicotine patches and gum, although useful for smoking cessation programs, may not be useful for local tissue optimization. We now routinely check vitamin D levels in all cases of delayed or failed osseous healing. Supplementation is usually 50,000 units per week for several weeks but underlying causes of the deficiency should be sought and corrected. Consultation with a primary care physician will help stabilize chronic medical conditions in many patients.

 

The limb is also evaluated for its ability to tolerate surgical intervention. Multiply operated limbs are B local by definition and heavily scarred and immobilized tissues may present risks for subsequent wound healing. Some patients may not be candidates or may not tolerate the extensive surgery that is required, and therefore compromises in treatment and patient expectations may be necessary. Many surgeons are now opting to treat exposed bone with a vacuum-assisted closure (VAC) device. Although this can often produce a healthy granulating tissue bed, it should be remembered that the underlying bone is compromised and has a higher risk of nonunion and infection. Another problem is that the soft tissue envelope tends to be an adherent layer of scar over the bone, which may not tolerate secondary surgery well. Secondary surgery under these circumstances may well result in further infection. For this reason, we still advocate the use of healthy muscle or fascial flaps that not only help being an external blood supply to the surface of the bone but can better tolerate subsequent surgical procedures.

 
Diagnostic Evaluation
 

Initially, laboratory testing including assessment of the WBC, ESR, and CRP is undertaken. If these tests are negative and there is no further reason to suspect infection, then we treat the patient as having an aseptic nonunion but we will pay attention to our intraoperative findings. If there is any indication of infection despite normal laboratory findings, we obtain intraoperative cultures or undertake a biopsy and await results. One common scenario is a presumed aseptic case where routine cultures end up growing a few colonies of bacteria. The issue is whether the culture results represent a real infection or contamination. In these cases, we discuss the surgical findings with the infectious disease specialist who explains their assessment of the validity of the cultures. If we believe that the risk of infection is low, we may cover the patient with a short course of culture-specific oral antibiotics. However, if we believe that the risk is high, we use a longer course of antibiotic treatment. We have found that even when there is little diagnostic and operative evidence of infection, patients may still develop later infection. We have no way of knowing if the subsequent infection was a resurgence of an old occult infection or a secondary infection from the recent surgical intervention. A recent study found that over 20% of nonunion cases, that had cultures taken intraoperatively, had positive cultures. These patients were given antibiotics and just over 2% developed infection from the same organism as was cultures preoperatively.120

 

In cases in which we suspect infection but do not know the organism, we will often remove the initial hardware and then take numerous cultures and biopsy samples of bone and soft tissue (often six or more). We will then temporarily stabilize the bone in the least invasive manner using a cast, brace, or monolateral external fixator. Sometimes it is helpful to obtain two different sets of cultures. One set of cultures is obtained from the most suspicious areas during the initial part of the surgical procedure. The second set of cultures is obtained after debridement from the margins of the tissue bed. If this methodology is used, one can assess whether the debridement was adequate, especially if the initial cultures were positive. If we remain uncertain about the extent of the infection, we will attempt to use MRI with contrast to determine the intramedullary and soft tissue extent of the infection and then plan our treatment accordingly. Unfortunately, in a majority of cases, there is implanted metal, which makes the use of MRI less applicable. When possible, we use scintigraphic studies preoperatively despite their limitations. We have anecdotally noted significant variations in the accuracy of the readings between various radiologists and encourage working with a few radiologists who are interested and experienced with musculoskeletal infection. Because of our own findings and those in the literature, we now depend less on scintigraphy than on other signs and generally no longer use the red cell scan. The initial findings of PET scanning are encouraging.

 
Treatment
 

Once infection has been confirmed, an organism is identified, and the extent of the infection is delineated, we decide whether the goal is to cure the infection, suppress the infection, or recommend amputation. In compromised hosts, cure can usually be achieved only by complete excision of all the infected tissue, which often means that amputation is required. In healthier hosts, marginal resection leaving some bacteria behind or even intralesional resections when the infection is periarticular can lead to cure with appropriate antibiotic therapy. Generally speaking, our preference is to advise the patient that resection with a clean margin has the best chance of cure.

 

If bone resection and limb salvage are chosen, we follow the general principles that bone defects of 6 cm or greater require bone transport with distraction osteogenesis, whereas smaller defects can often undergo bone grafting. In the tibia, we prefer the posterolateral tibia-pro-fibula technique, but in some cases we will undertake central bone grafting. We try to avoid the exclusive use of demineralized bone matrix (DBM) and allograft because we have found a relatively low incidence of bone union. The low success rates using DBM products may be because of the poor vascularity found in such tissue beds and patients. Anecdotally, we have noted cases where patients present years after failed DBM grafting of the distal tibia, and during reoperation the original DBM material appears to be unchanged. This indicates failure of angiogenesis (Fig. 26-20). DBM reports in the literature are limited but they do not support its general use as a bone graft substitute for nonunions, especially if there is bone loss. Ironically, cases in which bone graft is most needed, such as those where there is poor bone vascularity or a compromised host, are those in which DBM is of least value and the success of DBM may well be in those cases where bone graft is not needed.132

 
Figure 26-20
An intraoperative photograph of a distal tibial nonunion.
 
At the time of surgery the demineralized bone matrix (DBM) that was placed in situ over 5 years earlier appears to have changed little. Although DBM may be considered an inductive and conductive agent, its effects are weak to moderate at best, and without an improvement in bone vascularity, it may be of very limited value in those cases where it is needed the most.
At the time of surgery the demineralized bone matrix (DBM) that was placed in situ over 5 years earlier appears to have changed little. Although DBM may be considered an inductive and conductive agent, its effects are weak to moderate at best, and without an improvement in bone vascularity, it may be of very limited value in those cases where it is needed the most.
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Figure 26-20
An intraoperative photograph of a distal tibial nonunion.
At the time of surgery the demineralized bone matrix (DBM) that was placed in situ over 5 years earlier appears to have changed little. Although DBM may be considered an inductive and conductive agent, its effects are weak to moderate at best, and without an improvement in bone vascularity, it may be of very limited value in those cases where it is needed the most.
At the time of surgery the demineralized bone matrix (DBM) that was placed in situ over 5 years earlier appears to have changed little. Although DBM may be considered an inductive and conductive agent, its effects are weak to moderate at best, and without an improvement in bone vascularity, it may be of very limited value in those cases where it is needed the most.
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Bone morphogenetic proteins (BMPs) show significant promise and they are a much more powerful inductive agent than DBM. Currently surgeons still have to use them “off-label” as they have not been released for general use. There are numerous anecdotal cases of their successful use in nonunion and infection surgery, and their usefulness in limb salvage is unquestionable. However, there are some concerns about their potency and their use in females considering pregnancy within a year of its use.

 

The newer technique of graft harvest with the RIA has been shown to be successful for large defects and the graft harvested seems to have excellent osteogenic potential. Mixture with BMP may provide an even greater effect because the BMP is acellular and only an inductor, whereas the RIA aspirate supplies conductive elements and cellular components needed for healing. Experience with RIA has been positive.72,97

 

Another technique combining the use of RIA graft with an induced biomembrane has gained some popularity. The technique of Masquelet incorporates a cement spacer into the defect after bone resection. A biologic membrane grows over the spacer and the spacer is removed weeks to months later, once antibiotic elution has concluded. At the time of spacer removal, the membrane is maintained as best as possible to promote angiogenesis and a large-volume autograft, using iliac crest or RIA, is placed within the site.

 

If there is a sinus tract, we have found the technique of injecting diluted methylene blue dye into the sinus tract very helpful in localizing the path to any deep collection of fluid or sequestrum (Fig. 26-21). It helps minimize the amount of local tissue resection. The technique is relatively simple but does not always identify the whole lesion. Sinus tract resection is undertaken using a longitudinal elliptical skin incision to allow closure. The deep dissection follows the tract until the bone component is identified. Bone debridement is undertaken based on involvement. If the bone involvement is such that it is a Cierny III where there is axial stability, then all efforts are made to maintain axial stability, and avoid turning a type III lesion into a type IV, although sometimes this is not possible. Type IV lesions by definition require supplemental fixation and reconstruction. Some extensive type III lesions, although having some axial connection, are still unstable and may require additional treatment, thus essentially making them a type IV lesion. In salvageable type III lesions, we do not undertake a bulk resection and we often use a high-speed water-cooled burr to remove only as much bone as necessary.

 
Figure 26-21
Images depicting the debridement technique in a case of type III osteomyelitis with a sinus tract.
 
A, B: Methylene blue is injected into the sinus in the hope that it will find its way into the bone cavity and sequestrum. C: The skin resection is elliptical until the bone defect is identified. D: Because the lesion is type III and stable, we use a water-cooled high-speed burr to resect only as much bone as is required to remove the sequestrum and avascular tissue. E: This figure demonstrates the final resection and (F) demonstrates skin closure at follow-up.
A, B: Methylene blue is injected into the sinus in the hope that it will find its way into the bone cavity and sequestrum. C: The skin resection is elliptical until the bone defect is identified. D: Because the lesion is type III and stable, we use a water-cooled high-speed burr to resect only as much bone as is required to remove the sequestrum and avascular tissue. E: This figure demonstrates the final resection and (F) demonstrates skin closure at follow-up.
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Figure 26-21
Images depicting the debridement technique in a case of type III osteomyelitis with a sinus tract.
A, B: Methylene blue is injected into the sinus in the hope that it will find its way into the bone cavity and sequestrum. C: The skin resection is elliptical until the bone defect is identified. D: Because the lesion is type III and stable, we use a water-cooled high-speed burr to resect only as much bone as is required to remove the sequestrum and avascular tissue. E: This figure demonstrates the final resection and (F) demonstrates skin closure at follow-up.
A, B: Methylene blue is injected into the sinus in the hope that it will find its way into the bone cavity and sequestrum. C: The skin resection is elliptical until the bone defect is identified. D: Because the lesion is type III and stable, we use a water-cooled high-speed burr to resect only as much bone as is required to remove the sequestrum and avascular tissue. E: This figure demonstrates the final resection and (F) demonstrates skin closure at follow-up.
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In obvious type IV lesions, bone reconstruction is mandatory and it is a matter of how much reconstruction is required. We have found that bone transport is the most reliable method for reconstruction. This is discussed in Chapter 28. In certain areas, or in patients where transport may not be tolerated, the Masquelet technique or the use of bone cages with massive graft and BMP are the only other alternatives.

 

The use of antibiotic-coated nails for infected nonunions continues to evolve. Several reports have shown the efficacy of statically locked nails that are coated with a 2-mm cement mantle. We increasingly use this technique for infected long bone nonunions. The antibiotic cement must be mixed early in the procedure and the nail should be coated by the use of oversized cardiac pump tubing or other large bore tubing that is sterile and can be easily removed. We have not found chest tubes to be large enough. A 9-mm nail is selected for the tibia or femur. The nail and cement are prepared at the start of the case and the cement is allowed to cure on the nail for at least 45 minutes. The use of tubing insures a smooth, glass-like coating, which combined with the curing process, decreases the likelihood of debonding at insertion. The canal is overreamed by at least 5 mm to accommodate the nail and the cement. Once inserted, distal and proximal interlocking is undertaken using standard techniques. The nail permits early weight bearing. In cases of bone loss, we perform later grafting at 8 to 12 weeks, once the ESR and CRP tests are normal and the antibiotics have been stopped.45,100,103

 

In general, the mainstay of reconstruction for complex infection remains the bone transport techniques described by Ilizarov. These are described in detail in Chapter 28. Although this technique is not simple for either the patient or the surgeon, there are notable advantages compared with grafting techniques. These include the early development of regenerate bone soon after bone resection. If bone grafting is used, one must wait 8 weeks or longer as part of a staged reconstruction plan. Also, the effects of corticotomy include increasing blood flow in the limb for 4 to 6 weeks, and this may have a positive effect in infection cases. Most importantly, function is improved. The patient is encouraged to weight bear and to resume most activities of daily living. In many cases, patients can return to work, participate in recreational activities, and even swim. In cases where transport takes a considerable period or where transport has finished but one has to wait for maturation of regenerate bone, we have used long percutaneously inserted locked plates as an internal fixator that spans and protects maturing regenerate bone. This allows for early removal of the ring fixator (Fig. 26-22). Alternatively, some cases are amenable to transport over a nail (Fig. 26-23). We encourage surgeons who wish to treat bone infection to be familiar with Ilizarov method and to seek out appropriate training.

 
Figure 26-22
Radiographs of a long distal tibial transport.
 
The patient had a very large (∼16 cm) defect. A, B: To shorten transport time, bifocal transport was performed to an ankle fusion. C: At the time of docking, the subtalar joint was sacrificed and a retrograde hindfoot nail was inserted. This was overlapped with a long tibial locking plate. Screws were placed through the plate and nail. The regenerate was protected while simultaneously compressing the ankle docking site.
The patient had a very large (∼16 cm) defect. A, B: To shorten transport time, bifocal transport was performed to an ankle fusion. C: At the time of docking, the subtalar joint was sacrificed and a retrograde hindfoot nail was inserted. This was overlapped with a long tibial locking plate. Screws were placed through the plate and nail. The regenerate was protected while simultaneously compressing the ankle docking site.
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Figure 26-22
Radiographs of a long distal tibial transport.
The patient had a very large (∼16 cm) defect. A, B: To shorten transport time, bifocal transport was performed to an ankle fusion. C: At the time of docking, the subtalar joint was sacrificed and a retrograde hindfoot nail was inserted. This was overlapped with a long tibial locking plate. Screws were placed through the plate and nail. The regenerate was protected while simultaneously compressing the ankle docking site.
The patient had a very large (∼16 cm) defect. A, B: To shorten transport time, bifocal transport was performed to an ankle fusion. C: At the time of docking, the subtalar joint was sacrificed and a retrograde hindfoot nail was inserted. This was overlapped with a long tibial locking plate. Screws were placed through the plate and nail. The regenerate was protected while simultaneously compressing the ankle docking site.
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X
 
Figure 26-23
 
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
View Original | Slide (.ppt)
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
View Original | Slide (.ppt)
Figure 26-23
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
View Original | Slide (.ppt)
A, B: Images depicting length stable transport over a nail. In this case the patient had a sizeable bilateral defect. C: Functional treatment consisted of monolateral transport over a nail. D, E: At the time of docking, the bone ends were freshened and grafted, followed by a period of compression using the external fixator. Final healing occurred bilaterally.
View Original | Slide (.ppt)
X
 

A key component in the management of infection is functional rehabilitation. Often, the patients are extremely debilitated from years of disability because of their condition. Treatments that permit early weight bearing and encourage range of motion in adjacent joints promote physical and psychological well-being. It is unusual for treatment to fail because patients have been walking on their limb. Usually failure is caused by inadequate resection, inadequate stability, and inadequate biology.

 

It is very difficult for surgeons who operate infrequently on infection to achieve the results published by experts. Not only is bone transport labor intensive but successful treatment requires an integrated team who are trained and willing to meet the demands of the patients and to facilitate the work of the surgeon. It is also imperative to collaborate and enlist the expertise of colleagues in infectious disease, psychiatry, medicine, microvascular surgery, social work, physical therapy, and occupational therapy. All staff must also be aware of the special needs of these patients, many of whom have undergone multiple failed procedures. It is very common to find depression, anxiety, and other psychological issues in both patients and their families. In fact, the burdens of the caregiver have only recently been identified, with many caregivers reporting depression, financial loss, and other problems as they care for their family members.130

 

There is no doubt that, given the difficulties of treating bone infection, the best strategy is prevention. Surgeons have always been aware of this, but recently the medical community, patients, and bodies that fund medicine have become more aware of the problem. As a consequence of this, increased research is expanding our knowledge of surgical infection and this has significant implications for the prevention of osteomyelitis. There is more knowledge about the factors that increase the risk of infection. Controllable patient factors such as perioperative body temperature, glucose levels, and preoperative hygiene are being standardized. Improved surgical techniques and the optimization of the patient environment are also having an effect, and hopefully we will be able to minimize the incidence of osteomyelitis in the future.

 

Tribute to George C Cierny III

 

Orthopedic surgeons, particularly those who treat osteomyelitis, were saddened by the loss of George C. Cierny III last year on June 24th, 2013. Dr. Cierny was pivotal in studying and understanding the treatment of bone infections. His incredible energy and drive resulted in the accumulation of data that transformed the diagnosis, classification, and treatment of osteomyelitis. With his partner Dr. J. Mader (infectious disease), they developed the widely quoted and utilized Cierny-Mader classification of osteomyelitis. Dr. Cierny and Mader recognized the importance of the host, and approached osteomyelitis in a systematic way, intuitively recognizing the utility of applying the principles of tumor surgery to bone infections. His surgical skills and patient care were difficult to match, and he was internationally sought as a surgeon and speaker. Dr. Cierny was a physician who worked for weeks on a specific plan for each patient, revisiting the plan daily and making changes until he felt it was perfect. Perfection is what he demanded of himself and everyone around him, including the patient. This was particularly true in the operating room. He was a founding member of the Musculoskeletal Infection Society (MSIS), and has left behind a legacy for his colleagues, students, and friends. Orthopaedic surgeons are indebted to him and will miss his veracity and wisdom.

 

References

1.
Zalavras CG, Patzakis MJ, Holtom P. Local antibiotic therapy in the treatment of open fractures and osteomyelitis. Clin Orth Relat Res. 2004;427:86–93.
2.
Nelson CL. The current status of material used for depot delivery of drugs. Clin Orthop Relat Res. 2004;427:72–78.
3.
Anglen JO. Wound irrigation in musculoskeletal injury. J Am Acad Orthop Surg. 2001;9(4):219–226.
4.
Anglen JO. Comparison of soap and antibiotic solutions for irrigation of lower-limb open fracture wounds. A prospective, randomized study. J Bone Joint Surg Am. 2005;87(7):1415–1422.
5.
Anglen JO, Apostoles S, Christensen G, et al. The efficacy of various irrigation solutions in removing slime-producing Staphylococcus. J Orthop Trauma. 1994;8(5):390–396.
6.
Ash JM, Gilday DL. The futility of bone scanning in neonatal osteomyelitis: Concise communication. J Nucl Med. 1980;21(5):417–420.
7.
Benjamin JB, Volz RG. Efficacy of a topical antibiotic irrigant in decreasing or eliminating bacterial contamination in surgical wounds. Clin Orthop Relat Res. 1984;(184):114–117.
8.
Bhandari M, Schemitsch EH, Adili A, et al. High and low pressure pulsatile lavage of contaminated tibial fractures: An in vitro study of bacterial adherence and bone damage. J Orthop Trauma. 1999;13(8):526–533.
9.
Boerman OC, Rennen H, Oyen WJ, et al. Radiopharmaceuticals to image infection and inflammation. Semin Nucl Med. 2001;31(4):286–295.
10.
Borman TR, Johnson RA, Sherman FC. Gallium scintigraphy for diagnosis of septic arthritis and osteomyelitis in children. J Pediatr Orthop. 1986;6(3):317–325.
11.
Borrelli JJ, Prickett WD, Ricci WM. Treatment of nonunions and osseous defects with bone graft and calcium sulfate. Clin Orthop Relat Res. 2003;411:245–254.
12.
Boxma H, Broekhuizen T, Patka P, et al. Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: The Dutch Trauma Trial. Lancet. 1996;347(9009):1133–1137.
13.
Boyd JI 3rd, Wongworawat MD. High-pressure pulsatile lavage causes soft tissue damage. Clin Orthop Relat Res. 2004;(427):13–17.
14.
Carsenti-Etesse H, Doyon F, Desplaces N, et al. Epidemiology of bacterial infection during management of open leg fractures. Eur J Clin Microbiol Infect Dis. 1999;18(5):315–323.
15.
Casten DF, Nach RJ, Spinzia J. An experimental and clinical study of the effectiveness of antibiotic wound irrigation in preventing infection. Surg Gynecol Obstet. 1964;118:783–787.
16.
Cavanaugh DL, Berry J, Yarboro SR, et al. Better prophylaxis against surgical site infection with local as well as systemic antibiotics. An in vivo study. J Bone Joint Surg Am. 2009;91(8):1907–1912.
17.
Chacko TK, Zhuang H, Nakhoda KZ, et al. Applications of fluorodeoxyglucose positron emission tomography in the diagnosis of infection. Nucl Med Commun. 2003;24(6):615–624.
18.
Cierny G. Treating chronic osteomyelitis: evolving our antibiotic protocol. Paper presented at Musculoskeletal Infection Society, August, 2000.
19.
Cierny G, Mader JT, Pennick JJ. A clinical staging system for adult osteomyelitis. Contemp Orthop. 1985;10:17–37.
20.
Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003;(414):7–24.
21.
Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326(5):281–286.
22.
Collier BD. Scintigraphic diagnosis of acute bone infection: Is the red cell scan necessary? Personal communication.
23.
Condie JD, Fergerson DJ. Experimental wound infections: Contamination versus surgical technique. Surgery. 1961;50:367.
24.
Court-Brown CM, Keating JF, McQueen MM. Infection after intramedullary nailing of the tibia. Incidence and protocol for management. J Bone Joint Surg Br. 1992;74(5):770–774.
25.
Cunha B, Klein N. Bone and joint infections. In: Dee R, Hurst LC, Gruber MA, Kottmeier SA, eds. Principles of Orthopaedic Practice. 2nd ed. New York, NY: McGraw-Hill; 1997:317–344.
26.
Dankert J, Hogt AH, Feijen J. Biomedical polymers:Bacterial adhesion, colonization, and infection. CRC Crit Rev Biocompat. 1986;2:219–301.
27.
Datz FL. Minutes in Nuclear Medicine. 2nd ed. New York, NY: Appleton Century Crofts; 1983:82–85.
28.
Datz FL. Infection imaging. Semin Nucl Med. 1994;24(2):89–91.
29.
Datz FL. Abdominal abscess detection: Gallium, 111In-, and 99mTc-labeled leukocytes, and polyclonal and monoclonal antibodies. Semin Nucl Med. 1996;26(1):51–64.
30.
Datz FL, Seabold JE, Brown ML, et al. Procedure guideline for technetium-99m-HMPAO-labeled leukocyte scintigraphy for suspected infection/inflammation. Society of Nuclear Medicine. J Nucl Med. 1997;38(6):987–990.
31.
David R, Barron BJ, Madewell JE. Osteomyelitis, acute and chronic. Radiol Clin North Am. 1987;25(6):1171–1201.
32.
Dich VQ, Nelson JD, Haltalin KC. Osteomyelitis in infants and children. A review of 163 cases. Am J Dis Child. 1975;129(11):1273–1278.
33.
DiMaio FR, O’Halloran JJ, Quale JM. In vitro elution of ciprofloxacin from polymethylmethacrylate cement beads. J Orthop Res. 1994;12(1):79–82.
34.
Dirschl DR, Duff GP, Dahners LE, et al. High pressure pulsatile lavage irrigation of intraarticular fractures:Effects on fracture healing. J Orthop Trauma. 1998;12(7):460–463.
35.
Dirschl DR, Wilson FC. Topical antibiotic irrigation in the prophylaxis of operative wound infections in orthopedic surgery. Orthop Clin North Am. 1991;22(3):419–426.
36.
Duwelius PJ, Schmidt AH. Assessment of bone viability in patients with osteomyelitis:Ppreliminary clinical experience with laser Doppler flowmetry. J Orthop Trauma. 1992;6(3):327–332.
37.
Eckardt JJ, Wirganowicz PZ, Mar T. An aggressive surgical approach to the management of chronic osteomyelitis. Clin Orthop Relat Res. 1994;(298):229–239.
38.
Eisenstein BI. The polymerase chain reaction. A new method of using molecular genetics for medical diagnosis. N Engl J Med. 1990;322(3):178–183.
39.
Esterhai J, Alavi A, Mandell GA, et al. Sequential technetium-99m/gallium-67 scintigraphic evaluation of subclinical osteomyelitis complicating fracture nonunion. J Orthop Res. 1985;3(2):219–225.
40.
Esterhai JL Jr, Goll SR, McCarthy KE, et al. Indium-111 leukocyte scintigraphic detection of subclinical osteomyelitis complicating delayed and nonunion long bone fractures: A prospective study. J Orthop Res. 1987;5(1):1–6.
41.
Evans RP, Nelson CL, Harrison BH. The effect of wound environment on the incidence of acute osteomyelitis. Clin Orthop Relat Res. 1993;(286):289–297.
42.
Fennessy JM, Franzus M, Schlatterer D, et al. MRSA screening, surveillance, and control protocol in trauma patients. Poster. Annual Meeting of the AAOS, March 9–13, 2010.
43.
Fink-Bennett D, Balon HR, Irwin R. Sequential technetium-99m sulfur colloid/indium-111 white blood cell imaging in macroglobulinemia of Waldenstrom. Clin Nucl Med. 1990;15(6):389–391.
44.
Fischer B, Vaudaux P, Magnin M, et al. Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone-implanted metallic devices: Role of fibronectin in Staphylococcus aureus adhesion. J Orthop Res. 1996;14(6):914–920.
45.
Fuchs T, Stange R, Schmidmaier G, et al. The use of gentamicin-coated nails in the tibia: Preliminary results of a prospective study. Arch Orthop Trauma Surg. 2011;131(10):1419–1425.
46.
Gao Z, Tseng CH, Pei Z, et al. Molecular analysis of human forearm superficial skin bacterial biota. Proc Natl Acad Sci U S A. 2007;104(8):2927–2932.
47.
Gillespie WJ, Walenkamp G. Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures. Cochrane Database Syst Rev. 2001;1:CD000244.
48.
Graham GD, Lundy MM, Frederick RJ, et al. Predicting the cure of osteomyelitis under treatment: Concise communication. J Nucl Med. 1983;24(2):110–113.
49.
Greidanus NV, Masri BA, Garbuz DS, et al. Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty. A prospective evaluation. J Bone Joint Surg Am. 2007;89(7):1409–1416.
50.
Gristina AG, Barth E, Webb LX. Microbial adhesion and the pathogenesis of biomaterial-centered infections. In: Gustilo RB, Tsukayama DT, eds. Orthopaedic Infection. Philadelphia, PA: WB Saunders; 1989:3–25.
51.
Haas DW, McAndrew MP. Bacterial osteomyelitis in adults: Evolving considerations in diagnosis and treatment. Am J Med. 1996;101(5):550–561.
52.
Hartshorne MF, Graham G, Lancaster J, et al. Gallium-67/technetium-99m methylene diphosphonate ratio imaging: Early rabbit osteomyelitis and fracture. J Nucl Med. 1985;26(3):272–277.
53.
Hassinger SM, Harding G, Wongworawat MD. High-pressure pulsatile lavage propagates bacteria into soft tissue. Clin Orthop Relat Res. 2005;439:27–31.
54.
Hauet JR, Barge ML, Fajon O, et al. Sternal infection and retrosternal abscess shown on Tc-99m HMPAO-labeled leukocyte scintigraphy. Clin Nucl Med. 2004;29(3):194–195.
55.
Hauser CJ, Adams CA Jr, Eachempati SR. Surgical Infection Society guideline: Prophylactic antibiotic use in open fractures: An evidence-based guideline. Surg Infect (Larchmt). 2006;7(4):379–405.
56.
Hoch RC, Rodriguez R, Manning T, et al. Effects of accidental trauma on cytokine and endotoxin production. Crit Care Med. 1993;21(6):839–845.
57.
Hoeffel DP, Hinrichs SH, Garvin KL. Molecular diagnostics for the detection of musculoskeletal infection. Clin Orthop Relat Res. 1999;(360):37–46.
58.
Hughes DK. Nuclear medicine and infection detection: The relative effectiveness of imaging with 111In-oxine-, 99mTc-HMPAO-, and 99mTc-stannous fluoride colloid-labeled leukocytes and with 67Ga-citrate. J Nucl Med Technol. 2003;31(4):196–201; quiz 203–204.
59.
Jefferson KK. What drives bacteria to produce a biofilm? FEMS Microbiol Lett. 2004;236(2):163–173.
60.
Keating JF, Blachut PA, O’Brien PJ, et al. Reamed nailing of open tibial fractures: Does the antibiotic bead pouch reduce the deep infection rate? J Orthop Trauma. 1996;10(5):298–303.
61.
Kelly PJ. Infected nonunion of the femur and tibia. Orthop Clin North Am. 1984;15(3):481–490.
62.
Law HT, Flemming RH, Gilmore MF, et al. In vitro measurement and computer modelling of the diffusion of antibiotic in bone cement. J Biomed Eng. 1986;8(2):149–155.
63.
Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: What have we learned from 30 years of clinical trials? Int J Infect Dis. 2005;9(3):127–138.
64.
Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop Relat Res. 1997;(339):71–75.
65.
Lenarz CJ, Watson JT, Moed BR, et al. Timing of wound closure based on cultures obtained after debridement. J Bone Joint Surg Am. 2010;92:1921–1926.
66.
Mackowiak PA, Jones SR, Smith JW. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA. 1978;239(26):2772–2775.
67.
Mader JT, Calhoun J. Long-bone osteomyelitis diagnosis and management. Hosp Pract (Off Ed). 1994;29(10):71–76.
68.
Magnuson JE, Brown ML, Hauser MF, et al. In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: Comparison with other imaging modalities. Radiology. 1988;168(1):235–239.
69.
Mann S. Molecular recognition in biomineralization. Nature. 1988;332:119–124.
70.
Marsh JL, Prokuski L, Biermann JS. Chronic infected tibial nonunions with bone loss. Conventional techniques versus bone transport. Clin Orthop Relat Res. 1994;(301):139–146.
71.
May JW Jr, Jupiter JB, Weiland AJ, et al. Clinical classification of post-traumatic tibial osteomyelitis. J Bone Joint Surg Am. 1989;71(9):1422–1428.
72.
McCall TA, Brokaw DS, Jelen BA, et al. Treatment of large segmental bone defects with reamer-irrigator-aspirator bone graft. Technique and case series. Orthop Clin North Am. 2010;41(1):63–73.
73.
McCarthy K, Velchik MG, Alavi A, et al. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition. J Nucl Med. 1988;29(6):1015–1021.
74.
McKee MD, Wild LM, Schemitsch EH, et al. The use of an antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: Early results of a prospective trial. J Orthop Trauma. 2002;16(9):622–627.
75.
Meadows SE, Zuckerman JD, Koval KJ. Posttraumatic tibial osteomyelitis: Diagnosis, classification, and treatment. Bull Hosp Jt Dis. 1993;52(2):11–16.
76.
Merkel KD, Brown ML, Dewanjee MK, et al. Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study. J Bone Joint Surg Am. 1985;67(3):465–476.
77.
Merkel KD, Brown ML, Fitzgerald RH Jr. Sequential technetium-99m HMDP-gallium-67 citrate imaging for the evaluation of infection in the painful prosthesis. J Nucl Med. 1986;27(9):1413–1417.
78.
Modic MT, Feiglin DH, Piraino DW, et al. Vertebral osteomyelitis: Assessment using MR. Radiology. 1985;157(1):157–166.
79.
Molina-Murphy IL, Palmer EL, Scott JA, et al. Polyclonal, nonspecific 111In-IgG scintigraphy in the evaluation of complicated osteomyelitis and septic arthritis. Q J Nucl Med. 1999;43(1):29–37.
80.
Moscati RM, Mayrose J, Reardon RF, et al. A multicenter comparison of tap water versus sterile saline for wound irrigation. Acad Emerg Med. 2007;14(5):404–409.
81.
Moussa FW, Anglen JO, Gehrke JC, et al. The significance of positive cultures from orthopedic fixation devices in the absence of clinical infection. Am J Orthop. 1997;26(9):617–620.
82.
Moussa FW, Gainor BJ, Anglen JO, et al. Disinfecting agents for removing adherent bacteria from orthopaedic hardware. Clin Orthop Relat Res. 1996;(329):255–262.
83.
Murray CK, Hinkle MK, Yun HC. History of infections associated with combat-related injuries. J Trauma. 2008;64(3 suppl):S221–S231.
84.
Murray CK, Hsu JR, Solomkin JS, et al. Prevention and management of infections associated with combat-related extremity injuries. J Trauma. 2008;64(3 suppl):S239–S251.
85.
Naylor P, Jennings R, Myrvik Q. Antibiotic sensitivity of biomaterial-adherent Staphylococcus epidermidis. Orthop Trans. 1988;12:524–525.
86.
Nichols WW, Dorrington SM, Slack MP, et al. Inhibition of tobramycin diffusion by binding to alginate. Antimicrob Agents Chemother. 1988;32(4):518–523.
87.
Ochsner PE, Brunazzi MG. Intramedullary reaming and soft tissue procedures in treatment of chronic osteomyelitis of long bones. Orthopedics. 1994;17(5):433–440.
88.
Ostermann PA, Henry SL, Seligson D. [Value of adjuvant local antibiotic administration in therapy of open fractures. A comparative analysis of 704 consecutive cases]. Langenbecks Arch Chir. 1993;378(1):32–36.
89.
Owens BD, White DW, Wenke JC. Comparison of irrigation solutions and devices in a contaminated musculoskeletal wound survival model. JBJS (Am). 2009;91:92–98.
90.
Palestro CJ, Mehta HH, Patel M, et al. Marrow versus infection in the Charcot joint: Indium-111 leukocyte and technetium-99m sulfur colloid scintigraphy. J Nucl Med. 1998;39(2):346–350.
91.
Pape HC, Zwipp H, Regel G, et al. [Chronic treatment refractory osteomyelitis of long tubular bones–possibilities and risks of intramedullary boring]. Unfallchirurg. 1995;98(3):139–144.
92.
Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res. 1989;(243):36–40.
93.
Peters AM. The utility of [99mTc]HMPAO-leukocytes for imaging infection. Semin Nucl Med. 1994;24(2):110–127.
94.
Petrisor B, Jeray K, Schemitsch E, et al. Fluid lavage in patients with open fracture wounds (FLOW): An international survey of 984 surgeons. BMC Musculoskelet Disord. 2008;23(9):7.
95.
Poirier JY, Garin E, Derrien C, et al. Diagnosis of osteomyelitis in the diabetic foot with a 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy. Diabetes Metab. 2002;28(6 Pt 1):485–490.
96.
Pommer A, David A, Richter J, et al. [Intramedullary boring in infected intramedullary nail osteosyntheses of the tibia and femur]. Unfallchirurg. 1998;101(8):628–633.
97.
Porter, RM, Fangjun L, Carmencita P, et al. Osteogenic potential of reamer irrigator aspirator from patients undergoing hip arthroplasty. J Orthop Res. 2009;27(1):42–49.
98.
Quinn SF, Murray W, Clark RA, et al. MR imaging of chronic osteomyelitis. J Comput Assist Tomogr. 1988;12(1):113–117.
99.
Rang M. The Story of Orthopaedics. Philadelphia, PA: WB Saunders; 2000.
100.
Riel RU, Gladden PB. A simple method for fashioning an antibiotic cement-coated interlocking intramedullary nail. Am J Orthop (Belle Mead NJ). 2010;39(1):18–21.
101.
Rosenstein BD, Wilson FC, Funderburk CH. The use of bacitracin irrigation to prevent infection in postoperative skeletal wounds. An experimental study. J Bone Joint Surg Am. 1989;71(3):427–430.
102.
Rubin RH, Fischman AJ, Needleman M, et al. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin. J Nucl Med. 1989;30(3):385–389.
103.
Sancineto CF, Barla JD. Treatment of long bone osteomyelitis with a mechanically stable intramedullar antibiotic dispenser: Nineteen consecutive cases with a minimum of 12 months follow-up. J Trauma. 2008;65(6):1416–1420.
104.
Sankaran-Kutty M, Corea JR, Ali MS, et al. Squamous cell carcinoma in chronic osteomyelitis. Report of a case and review of the literature. Clin Orthop Relat Res. 1985;(198):264–267.
105.
Schauwecker DS. Osteomyelitis: Diagnosis with In-111-labeled leukocytes. Radiology. 1989;171(1):141–146.
106.
Schauwecker DS, Braunstein EM, Wheat LJ. Diagnostic imaging of osteomyelitis. Infect Dis Clin North Am. 1990;4(3):441–463.
107.
Schiesser M, Stumpe KD, Trentz O, et al. Detection of metallic implant-associated infections with FDG PET in patients with trauma: Correlation with microbiologic results. Radiology. 2003;226(2):391–398.
108.
Schmidt AH, Swiontkowski MF. Pathophysiology of infections after internal fixation of fractures. J Am Acad Ortho Surg. 2000;8(5):285–291.
109.
Seabold JE, Flickinger FW, Kao SC, et al. Indium-111-leukocyte/technetium-99m-MDP bone and magnetic resonance imaging: Difficulty of diagnosing osteomyelitis in patients with neuropathic osteoarthropathy. J Nucl Med. 1990;31(5):549–556.
110.
Seabold JE, Nepola JV, Conrad GR, et al. Detection of osteomyelitis at fracture nonunion sites: Comparison of two scintigraphic methods. AJR Am J Roentgenol. 1989;152(5):1021–1027.
111.
Seeley SK, Seeley JV, Telehowski P, et al. Volume and surface area study of tobramycin-polymethylmethacrylate beads. Clin Orthop Relat Res. 2004;(420):298–303.
112.
Segura AB, Munoz A, Brulles YR, et al. What is the role of bone scintigraphy in the diagnosis of infected joint prostheses? Nucl Med Commun. 2004;25(5):527–532.
113.
Svoboda SJ, Bice TG, Gooden HA, et al. Comparison of bulb syringe and pulsed lavage irrigation with use of a bioluminescent musculoskletal wound model. J Bone Joint Surg Am. 2006;88(10):2167–2174.
114.
Tang JS, Gold RH, Bassett LW, et al. Musculoskeletal infection of the extremities: Evaluation with MR imaging. Radiology. 1988;166(1 Pt 1):205–209.
115.
Tehranzadeh J, Wang F, Mesgarzadeh M. Magnetic resonance imaging of osteomyelitis. Crit Rev Diagn Imaging. 1992;33(6):495–534.
116.
Thomas LC, Gidding HF, Ginn AN, et al. Development of a real-time Staphylococcus aureus and MRSA (SAM-) PCR for routine blood culture. J Microbiol Methods. 2007;68(2):296–302.
117.
Toguchi A, Siano M, Burkart M, et al. Genetics of swarming motility in Salmonella enterica serovar typhimurium: Critical role for lipopolysaccharide. J Bacteriol. 2000;182(22):6308–6321.
118.
Toh CL, Jupiter JB. The infected nonunion of the tibia. Clin Orthop Relat Res. 1995;(315):176–191.
119.
Tompkins LS. The use of molecular methods in infectious diseases. N Engl J Med. 1992;327(18):1290–1297.
120.
Tornetta, P, Olszewski D, Jones, CB, et al. The fate of patients with a surprise positive culture after nonunion surgery. AAOS 2011, San Diego.
121.
Tsukayama DT. Pathophysiology of posttraumatic osteomyelitis. Clin Orthop Relat Res. 1999;(360):22–29.
122.
Valenziano CP, Chattar-Cora D, O’Neill A, et al. Efficacy of primary wound cultures in long bone open extremity fractures: Are they of any value? Arch Orthop Trauma Surg. 2002;122(5):259–261.
123.
Van Nostrand D, Abreu SH, Callaghan JJ, et al. In-111-labeled white blood cell uptake in noninfected closed fracture in humans: Prospective study. Radiology. 1988;167(2):495–498.
124.
Wald ER, Mirro R, Gartner JC. Pitfalls on the diagnosis of acute osteomyelitis by bone scan. Clin Pediatr (Phila). 1980;19(9):597–601.
125.
Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: A review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med. 1970;282(4):198–206.
126.
Watnick P, Kolter R. Biofilm, city of microbes. J Bacteriol. 2000;182(10):2675–2679.
127.
Weiland AJ, Moore JR, Daniel RK. The efficacy of free tissue transfer in the treatment of osteomyelitis. J Bone Joint Surg Am. 1984;66(2):181–193.
128.
Wheat J. Diagnostic strategies in osteomyelitis. Am J Med. 1985;78(6B):218–224.
129.
Wolf G, Aigner RM, Schwarz T. Diagnosis of bone infection using 99m Tc-HMPAO labelled leukocytes. Nucl Med Commun. 2001;22(11):1201–1206.
130.
Ziran BH, Barrette-Grishow MK, Hull TF. Hidden burdens of orthopedic injury care: The lost providers. J Trauma. 2009;66(2):536–549.
131.
Ziran BH, Rao N, Hall RA. A dedicated team approach enhances outcomes of osteomyelitis treatment. Clin Orthop Relat Res. 2003;414:31–36.
132.
Ziran BH, Smith WR, Morgan SJ. Use of calcium-based demineralized bone matrix/allograft for nonunions and posttraumatic reconstruction of the appendicular skeleton: Preliminary results and complications. J Trauma. 2007;63(6):1324–1328.