1
THE KURSK STATE MEDICAL UNIVERSITY
Department of surgical diseases № 1
Osteomyelitis
Information for self-training of English-speaking students
The chair of surgical diseases N 1 (Chair-head - prof. S.V.Ivanov)
By ass. professor I.S. IVANOV
KURSK-2010
INTRODUCTION
Osteomyelitis is a difficult-to-treat infection of bone and bone marrow. It is progressive and results in inflammatory destruction of the bone, bone necrosis, and new bone formation. Bacterial osteomyelitis causes substantial morbidity worldwide, despite continued progress toward understanding its pathophysiology and optimal management.
The approach to osteomyelitis depends upon the route by which bacteria gained access to bone, bacterial virulence, local and systemic host immune factors, and patient age. While imaging studies and nonspecific blood tests may suggest the diagnosis, an invasive technique is generally required to identify the causative pathogens. Antibacterial regimen selection has been largely guided by knowledge of the relative activities and pharmacokinetics of individual drugs, supported by data from animal models.
Definitive therapy often requires a combined medical and surgical approach. Newer microvascular and distraction osteogenesis techniques and the use of laser Doppler allow more complete surgical resection of infected material while maintaining function. Despite recent advances, aggressive medical and surgical therapy fails in many patients with osteomyelitis. More accurate diagnostic methods, better ways to assess and monitor the effectiveness of therapy, and novel approaches to eradicate sequestered bacteria are needed.
History of the Procedure: Osteomyelitis has been well known since antiquity.
Problem: Osteomyelitis results in inflammatory destruction of the bone, bone necrosis, and new bone formation. Three major categories of osteomyelitis exist, based upon pathogenic mechanisms of infection, as follows:
· Osteomyelitis following hematogenous spread of infection
· Osteomyelitis secondary to a contiguous focus of infection
· Osteomyelitis associated with vascular insufficiency
Three different subtypes of osteomyelitis are known: acute osteomyelitis, subacute osteomyelitis, and chronic osteomyelitis.
Frequency: The overall prevalence of acute osteomyelitis is 2 cases per 10,000 children.
Neonatal prevalence is approximately 1 case per 1000 children. The annual incidence in patients with sickle cell anemia is approximately 0.36%.
The prevalence of osteomyelitis after foot puncture may be as high as 16% (30-40% in patients with diabetes).
Excluding the axial skeleton, lower extremity osteomyelitis accounts for 90% of osteomyelitis cases and is much more common than upper extremity osteomyelitis, which accounts for 10% of extremity cases.
The most common bones involved in osteomyelitis in descending order are as follows:
· Tibia (50%) Femur (30%) Fibula (12%) Humerus (3%) Ulna (3%) Radius (2%)
The prevalence of chronic osteomyelitis is 2 cases per 10,000 people.
Most studies support the idea that incidence is similar in developed countries. In developing countries, incidence is higher due to higher incidence of puncture wounds, contaminated injuries, and less wound care.
Epidemiology of vertebral osteomyelitis
It is primarily a disease of adults; most patients are older than 50 years. Generally, the incidence increases progressively with each successive decade of life. Men are affected approximately twice as often as women in most case series. The reason for this male predominance is not clearly understood.
Reliable information regarding the overall incidence of vertebral osteomyelitis is difficult to obtain. However, most authorities believe that the overall incidence of vertebral osteomyelitis has steadily increased in recent years for 3 primary reasons: increasing rates of nosocomial bacteremia due to intravascular devices and other forms of instrumentation, increasing age of the population, and increasing injection drug use.
Etiology: While normal bone is resistant to infection, a number of conditions can predispose one to development of osteomyelitis, including the following:
· Large inoculation of an organism
· Trauma leading to bone damage or infarction
· Presence of a foreign body
· Illnesses compromising host defense
A single pathogenic organism is almost always recovered from the bone. The most common bone isolates are Staphylococcus species, the most common gram-negative organism is Pseudomonas aeruginosa, and the most common anaerobes are Peptostreptococcus species. However, in immunocompromised patients, other organisms, including fungi and mycobacteria, also must be considered.
Commonly isolated organisms in osteomyelitis can be summarized as follows:
· Hematogenous osteomyelitis (monomicrobial infection)
o Infants (<1 y)
§ Group B Streptococcus
§ Staphylococcus aureus
§ Escherichia coli
o Children (aged 1-16 y)
§ S aureus
§ Streptococcus pyogenes
§ Haemophilus influenzae
o Adults (>16 y)
§ S aureus
§ Coagulase-negative Staphylococcus species
§ Gram-negative bacilli
§ P aeruginosa
§ Serratia marcescens
§ E coli
· Contiguous focus osteomyelitis (polymicrobial infection)
o S aureus
o Coagulase-negative Staphylococcus species
o S pyogenes
o Enterococcus species
o Gram-negative bacilli
o Anaerobes
· Diabetic foot osteomyelitis (polymicrobial Infection)
o S aureus
o Streptococcus species
o Enterococcus species
o Proteus mirabilis
o P aeruginosa
o Anaerobes
Pathophysiology: The pathogenesis of osteomyelitis is multifactorial and poorly understood. Some important factors include the following:
· Virulence determinants of the organisms
· Underlying disease and the immune status of the host
· Type and location of the bone
It is clear that bacterial cells adhere to nucleated cells, platelets, and a variety of components of the extracellular bone matrix collagen and noncollagenous proteins.
Cellular and molecular pathogenesis
Cellular and molecular techniques provide new methods for determining the relative importance of the many potential virulence factors by facilitating study of the interaction between the host immune response and potential bacterial virulence factors. As an example, S aureus, which is an important cause of both hematogenous and contiguous focus osteomyelitis, produces a large number of extracellular and cell-associated factors that may contribute to virulence, including the following:
· Bacterial adherence: Bacteria adhere to bone by expressing receptors for the components of bone matrix including fibronectin, laminin, collagen, and bone sialoglycoprotein. Adherence appears to play a central role in the early stages of S aureus–induced osteomyelitis or arthritis. Expression of adhesins permits attachment of the pathogen to cartilage and synovial membrane. Strains positive for collagen adhesin are also associated with the production of high levels of immunoglobulin G (IgG) and interleukin (IL)–6. Bone infection has been speculated to be possibly prevented by an adhesin-derived vaccine.
· Proteolytic activity: Potential proteolytic activity present in normal joints is inhibited in the absence of infection. However, this protective effect may be lost with infection. In an in vitro model of adult chondrocytes inoculated with S aureus, for example, overall protein synthesis was reduced by 84%, with an increase in the release of collagenase and gelatinase.
· Resistance to host defense mechanisms: The ability of microorganisms to resist host defense mechanisms at both the cellular and matrix levels presents difficulties in the treatment of osteomyelitis. S aureus can survive intracellularly in cultured osteoblasts. Furthermore, the presence of arachidonic acid metabolites such as prostaglandin E2, which is a strong osteoclast agonist, decreases the bacterial inoculum needed to produce infection. Once the microorganisms adhere to bone, they express phenotypic changes that make them resistant to antimicrobial treatment.
o S aureus organisms express a 42-kd protein, protein A, which is bound covalently to the outer peptidoglycan layer of their cell walls. Protein A binds to the Fc portion of IgG on polymorphonuclear leukocytes, interfering with opsonization and phagocytosis of S aureus. This interference has been demonstrated in vitro and in animal models of subcutaneous abscess and peritonitis.
o S aureus also secretes 2 toxins: exotoxin and toxic shock syndrome toxin (TSST)–1, which exert a profound effect on the immune system when administered parenterally. The toxins act as superantigens and suppress plasma cell differentiation. They also stimulate production of cytokines, such as IL-1, interferon-gamma, and tumor necrosis factor-alpha. Animals infected with strains of S aureus isogenic for TSST-1 developed frequent and severe arthritis. Staphylococcal enterotoxin and TSST-1 subvert the cellular and humoral immune system, which may determine whether a local infection is eliminated or develops into osteomyelitis or septic arthritis.
· Nitric oxide: The increased turnover of bone in osteomyelitis suggests that the balance between bone formation and resorption is altered, an effect that may be mediated by nitric oxide. Greatly increased levels of nitric oxide and bone resorption have been recorded in the septic skeleton. This response may be driven by the increased levels of cytokines, enterotoxin, and TSST-1, which may stimulate nitric oxide production by endothelial, macrophage, and mesenchymal cells such as osteoblasts. Thus, while low concentrations of nitric oxide are typically thought to inhibit osteoclastic bone resorption, this response may be lost when cytokine and nitric oxide levels increase greatly in skeletal inflammatory disease. Adjunctive local treatment of osteomyelitis with nitric oxide synthetase inhibitors could be beneficial.
Routes of infection
As noted above, osteomyelitis develops via 3 major routes: hematogenous, contiguous focus spread, and vascular insufficiency.
· Hematogenous osteomyelitis: Hematogenous osteomyelitis is predominantly encountered in children; 85% of patients with hematogenous osteomyelitis are younger than 17 years, accounting for 20% percent of the total cases of osteomyelitis. In one study of 659 cases of S aureus osteomyelitis occurring in Denmark from 1959-1988, the number of hematogenous osteomyelitis cases declined, especially in children, and cases of vertebral osteomyelitis, more common in adults, increased. In children, the bone infection usually affects the long bones, while in adults, the lesion is usually located in the thoracic or lumbar vertebrae.
· Contiguous focus osteomyelitis without generalized vascular insufficiency: Osteomyelitis secondary to contiguous foci of infection accounts for at least one half of all cases and has increased in incidence. The organisms may be directly inoculated into the bone at the time of trauma, spread by nosocomial contamination during perioperative or intraoperative procedures, or extend from an adjacent soft tissue infection.
· Contiguous focus osteomyelitis with generalized vascular insufficiency: The primary cause of vascular insufficiency in patients with osteomyelitis is diabetes mellitus. The small bones of the feet, talus, calcaneus and distal fibula, and tibia are commonly involved. The patients in this group are aged 35-70 years. The infection frequently is initiated by a portal of entry for organisms, such as infected nail beds, cellulitis, or atrophic skin ulceration.
Diminished arterial blood supply has traditionally been considered to be the major predisposing factor for contiguous focus osteomyelitis with generalized vascular insufficiency in patients with diabetic foot. However, neuropathy now appears to be an equally important factor. Identifiable neuropathy as a complication of diabetes mellitus is present in approximately 80% of patients with foot disease. Neuropathy can cause foot ulceration through 3 main mechanisms, as follows:
· Decreased sensation leads to mechanical or thermal injuries in the unaware patient that can develop into skin ulcerations.
· Motor neuropathy affecting the intrinsic muscles of the foot predisposes affected persons to gait disturbances and foot deformities, such as hammertoe, clawtoe deformity, and Charcot foot. These anatomic alterations can lead to a maldistribution of weight and elevated focal pressure over the bony prominences. Subsequently, the increase in pressure where the foot contacts the ground or rubs against shoes can lead to skin ulceration.
· Autonomic neuropathy interferes with sweating; the resultant dry, cracked skin allows entry of microorganisms into the soft tissue.
A higher rate of nasal and skin colonization with S aureus, defects in host immunity, and impaired wound healing are all important factors in diabetic foot infection. Superficial fungal skin infections, which are common in patients with diabetes, also can facilitate bacterial entry through macerated or broken skin.
Pathological differences based on age
Basic differences exist in the pathology of osteomyelitis in infants, children, and adults.
In infants, small capillaries cross the epiphyseal growth plate and permit extension of infection into the epiphysis and joint space. This is a newly well-understood condition referred to as septic osteomyelitis in infants. The cortical bone of neonates and infants is thin and loose, consisting predominantly of woven bone, which permits escape of the pressure caused by infection but promotes rapid spread of the infection directly into the subperiosteal region. A large sequestrum is not produced because extensive infarction of the cortex does not occur; however, a large subperiosteal abscess can form.
In children older than 1 year, infection presumably starts in the metaphyseal sinusoidal veins and is contained by the growth plate. The joint is spared unless the metaphysis is intracapsular. The infection spreads laterally where it breaks through the cortex and lifts the loose periosteum to form a subperiosteal abscess.
In adults, the growth plate has resorbed, and the infection may again extend to the joint spaces, as in infants. In addition, the periosteum is firmly attached to the underlying bone; as a result, subperiosteal abscess formation and intense periosteal proliferation are observed less frequently. The infection can erode through the periosteum, forming a draining sinus tract.
Clinical: The clinical presentation and location of osteomyelitis differ in infants, children, and adults. In infants, medullary infection may spread to the epiphysis and joint surfaces through capillaries that cross the growth plate. In contrast, in children older than 1 year, the growth plate is avascular and infection is confined to the metaphysis and diaphysis. The joint is spared unless the metaphysis is intracapsular. Thus, cortical perforation at the proximal radius, humerus, or femur enables the infection to migrate to the elbow, shoulder, or hip joint, respectively, regardless of the age of the patient.
Hematogenous osteomyelitis
In hematogenous osteomyelitis, local symptoms referable to bones are more frequently absent in neonates than in children. In adults, soft tissue findings may be more prominent than bony involvement.
In infants, local findings that may lead the clinician to suspect osteomyelitis are usually absent in neonates. When they develop, local findings can include decreased motion of a limb and edema (pseudoparalysis) and joint effusion adjacent to the bone infection (present in 60-70% of cases).
Systemic symptoms are frequently present in S aureus osteomyelitis but may be absent when other pathogens are involved.
Children with hematogenous osteomyelitis, in contrast with neonates, typically have the following systemic symptoms:
· Abrupt fever
· Irritability
· Lethargy