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Bone and Joint Infections

Neal R. Chamberlain, Ph.D. Associate Professor

A.T. Still University/Kirksville College of Osteopathic Medicine

Department of Microbiology/Immunology

Specific Educational Objectives: The student should be able to:

1. Identify the causes of these diseases based on the age and other pertinent characteristics of the patient.
2. Know the common means of transmission and identify the major disease manifestations.
3. Know how to diagnose these infections.

OVERVIEW

There are two infectious diseases that will be discussed in this handout; osteomyelitis and septic arthritis. Osteomyelitis is an infection of the bone that can include the periosteum, medullary cavity, and cortical bone. Septic arthritis is an infection of surface of the cartilage that lines the joint and the synovial fluid that lubricates the joint. In both of these diseases Staphylococcus aureus is the most common cause of infection. Some exceptions do exist concerning the common cause of these diseases and they will be discussed in more detail (e.g., the most common cause of septic arthritis in a sexually active young adult is Neisseria gonorrhoeae).

Osteomyelitis tends to take some time to cause extensive damage to the bone (e.g., several weeks). Children and elderly adults are more likely to get these infections. Children usually get osteomyelitis of the long bones and the elderly usually get osteomyelitis of the vertebral body in the lumbar region of their spine. To successfully treat osteomyelitis requires several weeks (4-6 weeks) of antibiotic therapy. In cases of extensive bone damage surgery is also required to eliminate the infection.

Two different types of arthritis are associated with microbial infections; reactive and septic or infectious arthritis. Reactive arthritis is a sterile inflammatory process in the joint that can occur following a bacterial infection at a distant site in the body. Reactive arthritis also called Reiter’s syndrome and it causes urethritis, conjunctivitis, asymmetrical polyarthritis (e.g., ankles, knees, feet, and sacroiliitis) and a rash that occurs weeks after a bacterial infection. The most common cause of reactive arthritis is Chlamydia trachomatis. However, Campylobacter jejuni, Yersinia enterocolitica, Shigella, Salmonella and Streptococcus can all cause reactive arthritis. Reactive arthritis occurs more commonly in patients with human lymphocyte antigen B27 (HLA-B27).

Viruses, fungi and bacteria can all cause infectious arthritis. However bacteria cause the most damage to the joint and they cause septic arthritis. Septic arthritis is more commonly seen in children and in elderly adults. Unlike osteomyelitis, septic arthritis if not treated quickly can result in significant permanent damage to the joint and disability for the patient. Large numbers of white blood cells gather in the infected synovial fluid and produce high concentrations of inflammatory products. These inflammatory products cause most of the joint damage. The bacteria cause relatively little damage to the joint. Therefore treatment of septic arthritis requires immediate drainage of the joint followed by antibiotic treatment of 12 days to 4 weeks depending on the cause of the infection (i.e., 10-12 days for gonococcal septic arthritis and 3-4 weeks for nongonococcal septic arthritis).

OSTEOMYELITIS

Osteomyelitis is a progressive infection that can include infection of one or multiple parts of the bone (e.g., periosteum, medullary cavity, and cortical bone). It is usually a subacute to chronic infection that can cause severe disability if not properly treated. The disease if untreated progresses from inflammatory destruction of bone, to necrosis (sequestra) followed by new bone formation (involucrum).

Etiology

Osteomyelitis is usually a bacterial infection. Table 1 below contains the various types of osteomyelitis by age group and the common pathogens. Overall the most common cause of osteomyelitis is Staphylococcus aureus.

Other causes of this infection do vary depending on the age of the patient. If the vagina of a pregnant woman is colonized with Streptococcus agalactiae (group B Streptococcus) or Escherichia coli the neonate is more likely to aspirate these organisms during labor and delivery. S agalactiae and E coli are frequent causes of meningitis, pneumonia, and sepsis in newborn infants. These two organisms are also more frequent causes of osteomyelitis in newborns when compared to other age groups.

The elderly are more frequently infected with S aureus and gram-negative rod shaped bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens). Elderly patients are more likely to develop gram-negative infections of the blood stream following diverticulitis, acute prostatitis, and urinary tract infections. These organisms are also more likely to seed vertebrae in the lumbar region of the spine.

Certain patient factors or behaviors make them more likely to acquire a particular bacterial infection of the bone. Intravenous drug users are more likely to acquire Pseudomonas aeruginosa infections of the cervical vertebrae. Puncture wounds to the feet of persons while wearing athletic shoes are more likely to result in infections due to P aeruginosa or S aureus. Athletic shoes that are not allowed to thoroughly dry out between workouts are more likely to harbor increased numbers of P aeruginosa. Therefore a puncture wound of the foot while wearing athletic shoes is more likely to result in P aeruginosa infection. Osteomyelitis in those with sickle cell disease is most likely due to S aureus and Salmonella. Infections of patients with prosthetic joints are usually due to coagulase-negative Staphylococcus (e.g., S epidermidis) followed by S aureus.

Manifestations

The onset of symptoms can occur in a day or two as in acute osteomyelitis or take weeks to months in chronic osteomyelitis. Children are more likely to have acute long bone osteomyelitis. They will usually have chills, fever and malaise. There is usually pain and localized swelling and redness over the site of infection in the bone and guarding of the body part.

The elderly are more likely to have subacute or chronic vertebral osteomyelitis and usually mention localized lower back pain and tenderness with fever. A fever is not always present at time of presentation. In patients with chronic osteomyelitis the localized pain may come and go. Fever is usually NOT present.

Epidemiology

• Acute hematogenous osteomyelitis most commonly occurs in children and usually results in a single site of infection that involves the metaphysis of the long bones (e.g., tibia, femur and humerus).
• Around 50% of cases of osteomyelitis are in preschool children.
• The overall prevalence of osteomyelitis is 1 per 5000 children. The prevalence of osteomyelitis in neonates is 1 per 1000.
• The annual incidence of osteomyelitis in sickle cell patients is 0.36%.
• The prevalence of osteomyelitis after foot puncture can be as high as 16%.
• In diabetic patients with peripheral vascular disease the prevalence of osteomyelitis after foot puncture can be 30-40%.
• The male to female ratio of osteomyelitis is 2:1.
• Direct trauma and spread to the bone from a contiguous focus are more common among adults and adolescents than in children.
• Spinal osteomyelitis is more common in persons older than 45 years than in younger persons.
• When adults get osteomyelitis it usually involves the vertebral bodies. The lumbar vertebrae are most commonly affected followed by the thoracic and rarely the cervical vertebrae.
• Intravenous drug users are more likely to get vertebral infections in the cervical vertebrae.

Pathogenesis

The most common bones infected in children with osteomyelitis are the long bones. The long bones are the most frequent sites of infection because of the structure of the vessels supplying blood to the growth plates in these bones. The long bones of children and adolescents increase in length until maturity. For the growth plate to lengthen the long bone it needs nutrients. These nutrients are supplied by the nutrient artery. The nutrient artery connects to the nutrient vein via a venous capillary network. This capillary network forms sharp loops near the growth plate to supply the needed nutrients for growth. The narrow diameter and the sharp loops in these blood vessels can cause bacteria that may be in the bloodstream to make contact and attach to the endothelial cells lining the blood vessels in these regions. The bacteria can then multiply in the area and enter the epiphysis of the bone causing osteomyelitis. When a child matures growth plate closure occurs at each end of the long bone. The cartilage present in the growth plate is replaced with bone and infections in these areas of the bone become less common.

In adults the vertebrae contain small arteriolar vessels that are thought to trap bacteria in the bone. These vertebral arteries usually bifurcate and supply two adjacent vertebral bodies. This may explain why hematogenous osteomyelitis in adults usually involves two adjacent vertebrae and their intervening disc. A plexus of veins lacking valves called Batson’s plexus also surrounds the vertebrae. This venous system drains the bladder and pelvic regions. The most common cause of infection of the urinary tract is a gram-negative coliform called E coli. Other gram-negative coliforms can cause urinary tract infection. The organisms can get from the urinary tract to the vertebral bodies via Batson’s plexus and explains why gram-negative coliform infections of the vertebrae are more common in adult osteomyelitis.

Diagnosis

Peripheral white blood cell counts are usually normal. In chronic osteomyelitis the patient may have a normochromic normocytic anemia (i.e., anemia of chronic disease). In acute and chronic osteomyelitis the ESR is usually elevated. The ESR is usually higher in acute osteomyelitis than it is in chronic osteomyelitis. C-reactive protein levels are also elevated in acute and chronic conditions.

Diagnosis of osteomyelitis is usually made using radiological procedures that can include plane radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI). Plane radiographs have low sensitivity early on in acute osteomyelitis and require a loss of 50% of the bone calcium before osteomyelitis can be detected. This takes 2-3 weeks following onset of the disease. In long bone infections periosteal elevations may occur and soft tissue swelling may be detected. Radiographs of a patient with chronic osteomyelitis may detect increased calcification or bone sclerosis, sequestra, and involucra.

In vertebral osteomyelitis abnormalities might not be detectable by plane radiographs for 6-8 weeks. When abnormalities can be detected the bony plate of the vertebra appears irregular or “moth-eaten”. Collapse of the disc space is usually seen as the infection progresses. This collapse is best seen with CT scan. Cancer of the vertebrae can also cause this irregular “moth-eaten” look. Osteomyelitis almost always involves two adjacent vertebral bodies as well as the disc space whereas in most cases of vertebral cancer only one vertebral body is affected and the disc space is not affect.

CT scan can also be used and is more sensitive than plane radiographs. Oftentimes CT scans are used to guide needle biopsy and to determine the extent of surgical debridement required if surgery is needed.

MRI can also be used to detect osteomyelitis. When bone marrow dies it creates a unique MRI signal. It is more sensitive than plane films or CT scan and can be used much earlier in the disease process to detect abnormalities. Bone scans using technetium and gallium are useful however MRI is being used instead.

The organisms in many cases should be isolated from the bone infection to guide antimicrobial treatment. Two or three blood cultures may be useful in determining the cause of the infection. In adults with osteomyelitis deep tissue samples (e.g., needle biopsies) should be obtained and aerobic and anaerobic cultures of the sample requested. In spinal osteomyelitis needle biopsy using CT guidance is the procedure of choice for getting samples. Samples should be sent for bacteriological culture and pathological analysis. Pathological reports can be useful in culture negative samples to direct empiric antibiotic treatment. If the patient has a long bone infection frequently debridement, incision, and drainage of soft-tissue abscesses is required and samples from this material can be sent for culture.

In children deep tissue samples are not obtained to diagnose long bone infections. Deep tissue sampling can damage the epiphyseal plate resulting in impaired bone growth. Blood cultures should be obtained and if negative children are usually treated empirically.

Treatment and Prevention

There are three important steps to treating osteomyelitis in adults;

• Obtain adequate tissue for culture and histopathology. A sample deep in the infected tissue is needed. Bone biopsy is usually required.
• Design a specific antimicrobial regimen. Usually only one antimicrobial agent is needed if the organism is known.
• Surgery is not usually needed in acute hematogenous osteomyelitis surgery however, 4-6 weeks of antibiotic treatment is required. Patient with chronic osteomyelitis usually require surgery.

In children with long bone infections empiric intravenous antibiotic therapy can be started while the organism causing the infection is identified. When the organism is identified then in vitro susceptibility testing should be performed to determine what antibiotics the organism is susceptible to. Therapy requires intravenous administration of antibiotics for 4-6 weeks. The start of therapy begins on the day that effective antibiotic treatment was begun. That may or may not be the same day that empiric antibiotic therapy was started. If started early in acute hematogenous osteomyelitis surgery is rarely needed. However, if extensive necrotic bone is identified surgery may be necessary to get a cure. In children empiric therapy is oftentimes used because biopsies of the long bone can cause damage resulting in abnormal bone growth. This treatment should be given intravenously or orally for 4-6 weeks.

In adults with vertebral infections empiric therapy is not recommended. Cultures of the blood, bone, and soft tissue should guide antibiotic selection. Depending on the antibiotic given treatment can be either oral or intravenous however; it must also be given for 4-6 weeks. Surgical debridement is only required if there is instability, cord compression, or drainage of a soft tissue abscess is necessary.

If the patient has osteomyelitis due to methicillin sensitive Staphylococcus aureus the patient can be treated with nafcillin or oxacillin. However, if the infection is due to methicillin resistant Staphylococcus aureus (MRSA) the patient should receive vancomycin. Streptococcus infections can be treated with penicillin G. Gram-negative rod shaped bacterial infections can be treated with ciprofloxacin. However, if the osteomyelitis is due the following gram negative rod shaped bacteria; Serratia or Pseudomonas piperacillin-tazobactam and gentamicin should be used. If anaerobic bacteria are the cause of osteomyelitis then clindamycin or metronidazole can be used.

SEPTIC ARTHRITIS

Viruses, fungi and bacteria can all cause infectious arthritis however; bacterial arthritis causes the most damage and will be discussed in this chapter. Bacterial arthritis, also called septic arthritis, is a serious infection. If not treated quickly septic arthritis can result in significant permanent damage to the joint and disability for the patient.

Etiology

There are two major classes of septic arthritis: gonococcal and nongonococcal arthritis. Staphylococcus aureus is the most common cause of septic arthritis. S aureus is also the most common cause of nongonococcal arthritis. Neisseria gonorrhoeae is the most common cause of septic arthritis in young sexually active adults. Gram negative bacillary septic arthritis (e.g., Escherichia coli, Proteus, Serratia) is seen more frequently in the elderly. Streptococcus (e.g., viridans Streptococcus, S pneumoniae, and S agalactiae), account for 20% of cases of septic arthritis. Polymicrobial joint infections (5-10% of cases) and infection with anaerobic organisms (5% of cases) usually are a consequence of trauma or of abdominal infection.

Manifestations

Patients with nongonococcal septic arthritis usually present with the triad of fever, joint pain, and impaired range of motion. Elderly patients may be afebrile. In most of the cases of nongonococcal septic arthritis there is pain and swelling in a single joint. However, even in polyarticular septic arthritis S aureus is still the most common cause. S agalactiae (group B Streptococcus) usually infects the sacroiliac and sternoclavicular joints.

Polyarticular arthritis is commonly seen in gonococcal septic arthritis. Gonococcal septic arthritis is primarily an infection of sexually active young adults and teenagers and may present in one of two ways.

• Tenosynovitis, dermatitis, and polyarthritis syndrome or dermatitis-arthritis syndrome; the initial manifestations include fever, malaise, and arthralgias following an infection of the cervix, urethra, or pharynx. Later, inflammation of the tendons in the wrist, fingers and less commonly the ankles and toes is noted. Tenosynovitis includes tenderness over the tendon sheaths and exacerbation of pain during joint movement. Tenosynovitis in a young person is almost always due to disseminated gonococcemia. Skin lesions are multiple but seldom number more than 12 (Note: skin lesions from N meningitidis meningococcemia usually are more numerous). The lesions evolve over a few days from papular to pustular or vesicular to necrotic. This course may recur for several months. N gonorrhoeae is usually obtained in cultures of blood and mucosal surfaces but not in cultures of synovial fluid. Sixty percent of disseminated gonococcal infections are of this type. If untreated this syndrome can progress to purulent arthritis (i.e., N gonorrhoeae present in synovial fluid of the affected joints).

• Monoarticular arthritis without associated systemic symptoms. This disease usually occurs later than the tenosynovitis, dermatitis, and polyarthritis syndrome. Tenosynovitis, dermatitis, and polyarthritis syndrome may or may not precede this phase.

Epidemiology

• Most septic arthritis infections occur in very young and very old people and among intravenous drug users.
• Forty five percent of people with septic arthritis are over 65 years of age.
• Fifty six percent of patients with septic arthritis are male.
• About 20,000 cases of septic arthritis occur each year in the United States.
• Even with proper treatment about 1/3 of patients will have significant joint damage.
• Mortality rates depend on the agent causing the arthritis. In gonococcal joint infection the mortality rate is extremely low. If the infection is due to Staphylococcus aureus the mortality rate can be as high as 50%.
• In adults the knee is the most commonly infected joint followed by the hip, shoulder, ankle, and wrists. The elbow, interphalangeal, sternoclavicular, and sacroiliac joints are infected in very few septic arthritis cases.
• In children the hip joint is most commonly affected followed by the knee.
• Nearly 50% of patients who develop septic arthritis have some underlying chronic joint disease (e.g., rheumatoid arthritis, osteoarthritis).
• Nearly all cases of nongonococcal arthritis are monoarticular.
• Gonococcal septic arthritis is more likely to occur following an asymptomatic infection of the pharynx by N gonorrhoeae and it is more common in females.
• Polyarticular arthritis usually is observed in gonococcal septic arthritis.
• Gonococcal septic arthritis is more common in sexually active young adults and teenagers.
• Sexual interactions (i.e., homosexual, heterosexual, oral sex) are the means of transmission of N gonorrhoeae.  

Pathogenesis

Organisms can get in the joint by direct inoculation, contiguous spread from infected periarticular tissue, or by bacteremia. The most common route of infection is following a bacteremia. Causes of bacteremia leading to septic arthritis include urinary tract infection, intravenous drug use, intravenous catheters, endocarditis, and soft tissue infections.

Some bacteria have surface factors that promote their adherence to the joint. S aureus binds to articular sialoprotein. In adults with osteomyelitis, the arteriolar anastomosis between the epiphysis and the synovium can permit spread of organisms into the joint space.

The joint has several protective components. Synovial cells can phagocytize invaders. The synovial fluid itself is bactericidal. Previously damaged joints, especially joints with rheumatoid arthritis, are the more susceptible to infection. Other underlying conditions that make people more likely to develop septic arthritis include; osteoarthritis, systemic lupus erythematosus, minor trauma, and intra-articular injection of corticosteroids.

Damage of joint cartilage is the major debilitating result of septic arthritis. Following growth of the bacteria in the joint an acute inflammatory reaction results in infiltration of polymorphonuclear cells (PMN). Damage to joint cartilage is due to the synthesis of cytokines and inflammatory products by the PMN’s and bacterial factors (e.g., chondrocyte proteases of S. aureus) that cause damage.

The cytokines and inflammatory products produced by the PMN’s are thought to cause most of the damage to the joint. Infection with N gonorrhoeae induces a relatively mild influx of PMN’s into the joint. This explains why minimal joint destruction is usually observed in infections with this organism. Large numbers of PMN’s are recruited to the joint in S aureus infections resulting in significant damage to the joint cartilage.

Eventually, cartilage erosion occurs at the lateral margins of the joint. In time significant cartilage damage occurs followed by joint space narrowing. Significant damage to the joint can occur as soon as 3 days in untreated infections.

Diagnosis

A critical diagnostic test used in septic arthritis is the analysis of the synovial fluid. A white blood cell count, gram stain smear, and culture of the fluid are essential in determining the cause of septic arthritis. The most important use of synovial fluid analysis is to differentiate between noninflammatory, inflammatory and septic arthritis (See Table 2).

Blood cultures are useful in most cases of septic arthritis. If gonococcal septic arthritis is suspected pharyngeal, rectal, cervical, or urethral specimens should be obtained and swabbed on Thayer-Martin plates.

Treatment and Prevention

Nongonococcal septic arthritis treatment involves two essential components:

• Complete drainage and washing of the purulent exudate when possible by arthroscopy or by surgery. Allowing the activated PMN’s to remain in the joint will allow further release of more inflammatory mediators causing more joint damage.
• Intravenous administration of an appropriate antibiotic based on gram stain smear, culture results and clinical presentation. Antibiotic regimens are identical to those mentioned in the therapy section for osteomyelitis above except treatment is 3-4 weeks instead of 4-6 weeks.

Even with appropriate treatment one third of patients with nongonococcal septic arthritis will suffer significant joint damage. Elderly patients, patients with preexisting chronic joint disease, and those with prosthetic joints are more likely to have adverse outcomes.

Treatment of gonococcal septic arthritis requires complete drainage and washing of the purulent synovial fluid from the joint and antibiotic therapy with intravenous ceftriaxone for 24-48 hours after clinical improvement. Then switch to oral cefixime, ciprofloxacin, ofloxacin, or levofloxacin to complete a total of 7-10 days of therapy. Residual joint damage is unusual.

Prevention of nongonococcal arthritis involves avoiding joint trauma, and appropriate and timely treatment of infections (e.g., urinary tract infections, soft tissue infections, pneumonia). Prevention of gonococcal arthritis involves avoiding sexual partners that have gonorrhea, identifying and treating those with gonorrhea, and the use of safe sexual practices.

Revised 1/20/10

©2010 Neal R. Chamberlain, Ph.D., nchamberlain@atsu.edu

All rights reserved.

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