Return to syllabus

BONE AND JOINT INFECTIONS

Osteomyelitis

Septic Arthritis

General Goal: To know the cause of these diseases, the most common modes of transmission, the major manifestations, how to diagnose these infections and how to treat them.

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.

4. Know how to diagnose these infections.

5. Know how to treat these infections.

Lecture: Neal R. Chamberlain, Ph.D.

References: 

Osteomyelitis by A. Kumar, in Emedicine. http://www.emedicine.com/ped/topic1677.htm

Osteomyelitis by R. King, in Emedicine. http://www.emedicine.com/emerg/topic349.htm

Septic Arthritis by J. Brusch, in Emedicine.

http://www.emedicine.com/med/topic3394.htm

F.S. Southwick. Infectious Diseases in 30 Days. McGraw Hill. 2003. p. 344-360.

OSTEOMYELITIS

OVERVIEW

Osteomyelitis is a progressive disease that can include one or multiple parts of the bone. It can result in infection of the periosteum, medullary cavity, and/or cortical bone. It is 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) and new bone formation (involucrum).

There are several different types of osteomyelitis:

1. Acute osteomyelitis- evolves over several days to weeks
2. Chronic osteomyelitis- evolves over several weeks to months to years
3. Hematogenous osteomyelitis- result of bacteremic spread with seeding of the bacteria in bone. Usually seen in prepubertal children and the elderly.
4. Osteomyelitis secondary to contiguous spread- follows trauma, perforation or an orthopedic procedure.
5. Diabetic foot infection- contiguous spread to the bone associated with poor vascular supply.

ETIOLOGY

Osteomyelitis is usually a bacterial infection.

Microbiology of Osteomyelitis
Type of Osteomyelitis	Common Pathogens
Hematogenous (usually one organism)
Infant (<1 year)	Staphylococcus aureus Streptococcus agalactiae Escherichia coli
Children (1-16 years)	Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae
Adults (>16 years)	Staphylococcus aureus Coagulase-negative staphylococci Gram-negatives: Escherichia coli, Pseudomonas, Serratia
Contiguous Spread (polymicrobial)
Microbiology depends on the primary site of infection.	Staphylococcus aureus Streptococcus pyogenes Enterococcus Coagulase-negative staphylococci Gram-negatives Anaerobes
Diabetic foot (polymicrobial)	Staphylococcus aureus Streptococcus and Enterococcus Gram-negatives: Proteus mirabilis, Pseudomonas Anaerobes

Pseudomonas aeruginosa hematogenous infections are oftentimes seen in drug addicts and have a predilection for the cervical vertebrae.

Puncture wounds to the feet while wearing athletic shoes are more likely to result in infections due to Pseudomonas aeruginosa or Staphylococcus aureus.

Osteomyelitis in those with sickle cell disease is most likely due to Staphylococcus aureus and Salmonella species.

EPIDEMIOLOGY

Hematogenous osteomyelitis most commonly occurs in children and usually results in a single site of infection that involves the metaphysis of the long bones (commonly the tibia, femur and humerus). Hematogenous osteomyelitis is the most common source of this infection in children. About 50% of cases of osteomyelitis are in preschool children. Children usually have acute hematogenous osteomyelitis. The overall prevalence is 1 per 5000 children. The prevalence in neonates is 1 per 1000. The annual incidence 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 after foot puncture can be 30-40%. Male to female ratio is 2:1.

Direct trauma and contiguous focus osteomyelitis 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.

PATHOGENESIS

The most common sites of infection are the long bones in children and in the vertebrae in adults. The reason these are the most frequent sites of infection are due to the nature of the vessels supplying blood to these bones. In long bones of children bacteria tend to lodge in the small end vessels that form sharp loops near the epiphyses.

In the vertebral bodes of adults small arteriolar vessels are thought to trap bacteria. These vertebral arteries usually bifurcate and supply two adjacent vertebral bodies. This may explain why hematogenous osteomyelitis 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 and may explain why Gram-negative coliform infections of the vertebrae are more common in adult osteomyelitis.

MANIFESTATIONS

Long bone acute infections: chills, fever and malaise. Pain, localized swelling and redness over the site of infection in the bone and guarding of the body part are common.

Vertebral osteomyelitis: localized back pain and tenderness with fever. The fever is not always present at time of presentation.

Chronic osteomyelitis: localized pain that may come and go. Fever is usually NOT present.

In acute and chronic osteomyelitis the erythrocyte sedimentation rate (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

Peripheral WBC counts are usually normal. In chronic osteomyelitis the patient may have a normochromic normocytic anemia (anemia of chronic disease). The ESR and C-reactive protein levels are elevated however this is the case in many different inflammatory disease processes.

Diagnosis of osteomyelitis is usually made using radiological procedures: plane radiographs, CT scans, and MRI.

X-rays have low sensitivity early on in acute osteomyelitis and require a loss of 50% of the bone calcium before it can be detected by plane X-rays. 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.

X-rays 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 X-ray 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 vertebra can also cause this irregular “moth-eaten” look on X-ray. One way to tell the difference is that in osteomyelitis infection almost always involves two adjacent vertebral bodies as well as the disc space whereas in most neoplastic processes only one vertebral body is affected and the disc space is not affect.

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

MRI is also being used more in more to detect dead bone. When long bone marrow dies it creates a unique MRI signal. It is more sensitive than plain films or CT scan and can be used much earlier in the disease process to detect abnormalities.

Bone scans using technetium, gallium, etc. are useful however more and more 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 however in many cases blood cultures are negative.

Adults- deep tissue samples with aerobic and anaerobic culture are needed. 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 very useful in culture negative samples in directing empiric antibiotic treatment. If the patient has a long bone infection frequently debridement and/or incision and drainage of soft-tissue abscesses is required and samples from this material can be sent for culture.

Children- operative (needle biopsies etc.) are not done because they can damage the epiphyseal plate causing impaired bone growth. If blood cultures are negative children are usually treated empirically.

THERAPY

Three keys to therapy:

1. Obtain adequate tissue for culture and histopathology- a good sample deep in the infected tissue is needed. Bone biopsy is usually required.
2. Design a specific antimicrobial regimen- usually one agent if the organism is known.
3. Proper surgical management- usually in acute hematogenous osteomyelitis surgery is not needed however 4-6 weeks of antibiotic treatment is required. However in chronic osteomyelitis surgery is frequently required especially if significant amounts of necrosis has occurred in the bone.

Long bone infections- Empiric parenteral antibiotic therapy can be started until the organism(s) causing the infection are identified. Then the organism(s) is/are identified and in vitro susceptibility testing is performed to determine what antibiotics the organism(s) is/are sensitive to. Then definitive therapy can commence. Therapy requires parenteral administration of antibiotics for 4-6 weeks. The start of therapy begins on the day that the effective antibiotic treatment was begun. That may or may not be the same day that empiric antibiotic therapy was begun.

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 may be given parenterally or orally for 4-6 weeks.

Vertebral infections- empiric therapy is not recommended for this infection. Cultures of the blood, bone and soft tissue should guide the selection of antibiotic therapy. Depending on the antibiotic given treatment can be either oral or parenteral 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.

S. aureus- methicillin-sensitive organisms are usually treated with nafcillin or oxacillin; MRSA organisms are usually treated with vancomycin.

Streptococci: Penicillin G

Enteric Gram-negatives: ciprofloxacin

Serratia or Pseudomonas: piperacillin-tazobactam and gentamicin

Anaerobes: clindamycin or metronidazole

OSTEOMYELITIS SECONDARY TO A CONTIGUOUS INFECTION

The clinical picture is a little more complicated. Radiologic examinations and other imaging procedures are oftentimes not diagnostic. Below are some examples of the common osteomyelitis infections secondary to a contiguous infection.

1. Comminuted or complex bone fracture- following corrective surgery pain improves and the patient can mobilize the injured limb. As the patient begins to put weight on the limb pain reappears. A mild fever is noted and the wound gets more erythematous accompanied by a slight discharge.
2. Acute purulent frontal sinusitis that spreads to the frontal bone causing edema of the forehead (Pott’s puffy tumor).
3. Dental root infection that leads to local bone infection- swelling and pain over the infected dental root and jawbone.
4. Deep-seated pressure sores that spread to the underlying bone (usually the sacrum).

ETIOLOGY

Usually are polymicrobial (see table above). Staphylococcus aureus is the most frequently isolated.

Pseudomonas aeruginosa is common in chronic osteomyelitis following contiguous spread and in comminuted fractures as well as puncture wounds to the heel.

Anaerobes are common in osteomyelitis of the mandible, secondary to pressure sores and following human and animal bites.

THERAPY

See above

DIABETIC FOOT INFECTION OR OSTEOMYELITIS SECONDARY TO VACULAR INSUFFICIENCY

Frequently seen in patients with diabetes and vascular impairment and is almost exclusively located on the lower extremities. The infection starts very slowly in a patient that complains of intermittent claudication in an area of previously traumatized skin. Cellulitis may be minimal. The infection progressively burrows it way to the underlying bone (e.g. toe, metatarsal head, tarsal bone).

Examination reveals either no pain (in patients with advanced neuropathy) or excruciating pain if bone destruction has been acute. Crepitus may be felt sometimes and indicates infection with either anaerobes or Enterobacteriaceae. Physical exam should include assessment of vascular supply and if neuropathy is present.

ETIOLOGY, DIAGNOSIS AND TREATMENT

Any one of many different bacteria can be the cause (see table above). The most common cause is Staphylococcus aureus.

Diagnosis involves use of a sterile surgical probe to see if by gently advancing the probe you can reach bone. A plain radiograph is also essential in diagnosis. If bone is detected by probing treatment for osteomyelitis is recommended.

If bone is not reached then treatment for soft tissue infection is needed however occult osteomyelitis maybe present. To ensure this is not the case a radiograph 2 weeks following treatment should be performed.

Prognosis for treatment is poor because of the poor vascular supply. Treatment usually involves debridement and 4-6 weeks of parenteral antibiotic treatment.

If this does not work attempts to revascularize the tissue should be tried. If this does not work and the infection does not go away amputation may be required.

SEPTIC ARTHRITIS

OVERVIEW

Viruses, fungi and bacteria can all cause infectious arthritis however; bacterial arthritis causes the most damage. Bacterial arthritis is a serious infection in that if not treated quickly can result in significant permanent damage to the joint and disability for the patient.

Reactive arthritis, a sterile inflammatory process in the joint that may result from an infection at a distant site in the body, will not be discussed in detail here. Reactive arthritis includes Reiter’s syndrome (urethritis, conjunctivitis, asymmetrical polyarthritis (ankles, knees, feet, and sacroiliitis) and rash that occurs weeks after an infection with C. trachomatis, Campylobacter jejuni, Yersinia enterocolitica, Shigella or Salmonella and poststreptococcal reactive arthritis (see Jones criteria for acute rheumatic fever).

ETIOLOGY

There are two major classes of bacterial/suppurative arthritis: gonococcal and nongonococcal.

Staphylococcus aureus is the most common cause of infectious arthritis.

Other common causes in:

1. young adults include Neisseria gonorrhoeae. N. gonorrhoeae is the most common cause of septic arthritis in younger sexually active adults.
2. the elderly include Gram negative bacilli.

Streptococcal species, such as Streptococcus viridans, Streptococcus pneumoniae, and Streptococcus agalactiae (group B streptococci), account for 20% of cases. Aerobic gram-negative rods are involved in 20-25% of cases. Most of these infections occur in very young and very old people and among people who abuse intravenous drugs.

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.

Mycobacteria and fungi can also cause monoarticular arthritis. Arthritis following infection with Borrelia burgdorferi can cause an acute transient arthritis. Viruses such as parvovirus B19, hepatitis B, rubella, mumps and HIV can also cause acute arthritis.

Almost any microorganism can cause infective arthritis.

EPIDEMIOLOGY

About 20,000 cases of suppurative arthritis occur each year in the U.S. (7.8 cases per 100,000 person-years). The incidence of disseminated gonococcal infection is 2.8 cases per 10,000 person-years.

Even with proper treatment about 1/3 of patients will have significant joint damage. Morbidity rates depend on the agent causing the arthritis. In gonococcal joint infection the morbidity rate is extremely low however; if the infection is due to Staphylococcus aureus the morbidity rate can be as high as 50%. Forty five percent of people with septic arthritis are over 65 years of age. Fifty six percent with septic arthritis are male.

In adults knee is the most commonly infected joint (50%) followed by the hip (20%), shoulder (8%), ankle (7%) and wrists (7%). The elbow, interphalangeal, sternoclavicular, and sacroiliac joints are infected in 1-4% of septic arthritis cases.

In children the hip joint is most commonly affected (60%) followed by the knee (35%).

Almost 50% of patients who develop septic arthritis have some underlying chronic joint disease (rheumatoid arthritis, osteoarthritis).

PATHOGENESIS

The joint normally has several protective components. Synovial cells can phagocytize invaders. The synovial fluid itself has a lot of bactericidal activity. 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 abuse, intravenous catheters, endocarditis (Staphylococcus aureus or Enterococcus), and soft tissue infections.

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 (SLE), minor trauma, intra-articular injection of corticosteroids.

Some microorganisms 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 also permit spread of organisms into the joint space.

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 PMNs. Damage to joint cartilage is due to the synthesis of cytokines and inflammatory products made by the PMN’s and bacterial production of factors (chondrocyte proteases of S aureus) that cause damage.

The cytokines and inflammatory products made 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 into the course of an untreated infection.

MANIFESTATIONS

Patients with septic arthritis usually present with the triad of fever (40-60%), pain (75%), 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 (monoarticular arthritis; 85-90%). Polyarticular arthritis is seen in gonococcal arthritis, viral infections, Lyme disease, reactive arthritis and a variety of noninfectious arthritides (rheumatoid arthritis). If septic arthritis is polyarticular Staphylococcus aureus is still the most common cause.

Streptococcus agalactiae usually infects the sacroiliac and sternoclavicular joints.

Gonococcal musculoskeletal involvement 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, while lesions from meningococcemia may number more than 100. The lesions evolve over a few days from papular to pustular or vesicular to necrotic. This course may recur for several months. Findings on cultures of blood and mucosal surfaces often are positive; findings on cultures of joint fluid usually are negative. Sixty percent of disseminated gonococcal infections are of this type. If untreated this syndrome can progress to purulent arthritis.

• Monoarticular arthritis without associated systemic symptoms, tenosynovitis, or skin lesions characterizes disease that begins later after gonococcal dissemination than does dermatitis arthritis syndrome. Dermatitis-arthritis syndrome may or may not precede this phase.

DIAGNOSIS

A critical diagnostic test is the analysis of the synovial fluid. A white blood cell count, Gram stain smear and culture of the fluid are very helpful in determining the cause of the arthritis.

Blood cultures are also useful in a significant number of cases. In cases you suspect gonococcal infection pharyngeal, rectal, cervical, or urethral specimens placed on Thayer-Martin plates are also very helpful.

THERAPY

Nongonococcal septic arthritis treatment involves two essential components:

1. Complete drainage and washing of the purulent exudate when possible by arthroscopy (knee infections) or by surgery (hip infections). Allowing the activated PMN’s to remain in the joint will allow further release of more inflammatory mediators causing more irreversible joint damage.

2. Parenteral administration of an appropriate antibiotic- based on Gram stain smear, culture results and/or 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 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 is the same as for nongonococcal septic arthritis however; antibiotic therapy is a little different. It involves parenteral 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.

Revised 9/9/05

©2004 Neal R. Chamberlain, Ph.D., All rights reserved.

Return to syllabus