A 16-year-old boy injures his lower left thigh during a high school football game. The pain associated with this injury is so intense that he has to leave the game. The pain subsides for several hours but returns during the night, and the boy develops chills followed by a fever of 39.5ºC. A physician examines him the next morning and notices that the lower left thigh is hot, swollen, and tender. The knee joint appears normal and has a full range of motion. The patient has a temperature 38.3ºC. The physician notes several small boils on the boy's neck and chest. Some of these are scarred and crusted, and the patient admits that he has been squeezing them during the past few days. X-rays of the left femur indicate soft tissue swelling without any obvious abnormalities of the bone.

Question 1.1: What is your diagnosis?

The x-rays eliminate the possibility of a bone fracture. The fever and chills, in combination with pain and inflammation over the injured area, indicate an infection. In general, the symptoms are consistent with a diagnosis of acute osteomyelitis, a bone infection. The normal appearance of the bone in x-rays does not rule out this diagnosis because it typically takes at least 10 days for the infection-related bone damage to become so extensive that it is visible in plain radiographs.

Question 1.2: How would you handle this case?

This is a potentially dangerous situation because the infection can become chronic, after which it may be very difficult to treat and, as a result, lead to serious damage. The patient should be hospitalized, and antibiotic therapy should be started immediately. Blood cultures should be ordered in hopes of identifying the causative agent. If you want further confirmation of acute osteomyelitis, you might order tests for erythrocyte sedimentation rate (ESR) and C-reactive protein.

Test Results:

ESR and C-reactive protein are both slightly elevated. Blood cultures are positive, and a Gram-positive coccus is isolated from them. This isolate is coagulase positive and catalase positive.

Question 1.3: What is the probable causative agent?

The lab results indicate that the probable causative agent of the bone infection is Staphylococcus aureus. S. aureus is the most frequent cause of bacterial osteomyelitis and is isolated from >50% of the victims of this disease. It should be noted that blood cultures are positive in only about 1/3 of acute osteomyelitis cases. When blood cultures are negative, aspiration or biopsy of the bone for culture may be required to identify the causative agent with certainty.

Question 1.4: How did the patient's bone become infected?

Microorganisms enter bones by (1) the hematogenous route (hematogenous osteomyelitis) or (2) direct introduction, either from a contiguous focus of infection or by a penetrating wound. There is no history of a penetrating wound or contiguous infection in this case, so hematogenous spread is the most likely source of the boy's infection. This conclusion is further supported by the finding of S. aureus in the blood cultures. The S. aureus bacteremia probably was present at the time of the leg injury and may have come about when the boy manipulated the boils (typically caused by S. aureus) in his neck and chest. The trauma to the leg during the football game damaged the distal femur and most likely resulted in rupture of small vessels and formation of a hematoma or blood clot in the bone. The disruption of the normal anatomical barriers rendered the boy's bone more susceptible to infection by the S. aureus cells that were already circulating in his blood.

Question 1.5: What is the correct treatment for this disease?

Treatment of acute osteomyelitis requires a high daily dose of antibiotic that is continued for 4 to 6 weeks. The initial doses should be given intravenously. High doses are required to adequately penetrate bone tissue. Because the majority of cases are caused by S. aureus, empirical treatment should make use of a drug that is active against this agent (such as oxicillin, nafcillin, or a cephalosporin). Antibiotic therapy should then be adjusted (if necessary) after the causative agent is identified and characterized by the lab. (For example, infections caused by methicillin-resistant S. aureus are treated with vancomycin.) If fever and pain persist for 24-48 hours after antibiotic therapy is initiated, surgical drainage may be indicated.

Question 1.6: What is the prognosis?

If appropriate treatment is started early in the course of the infection, before much bone necrosis occurs, patients usually respond quickly. Prompt treatment is successful in >90% of cases.

Question 1.7: What can happen if this disease is mistreated or misdiagnosed?

As noted above, the infection can progress to chronic osteomyelitis, in which progressive ischemic necrosis of bone results in the separation of large devascularized fragments of bone (called sequestrum). When pus breaks through the cortex, superiosteal or soft tissue abscesses form, and the elevated periosteum deposits new bone (called involucrum) around the sequestra. Chronic osteomyelitis is characterized by a protracted clinical course. Sinus tracts between the bone and skin may drain purulent material and, occasionally, pieces of necrotic bone. Typically, there are periods of quiescence alternating with recurrent exacerbations (signaled by an increase in drainage, pain, and/or ESR). The following scenario describes what might happen in the present case if the initial diagnosis were missed.

Unfortunately, the physician who first treats the boy misses the diagnosis of osteomyelitis, gives the patient an oral antibiotic, and sends him home. Three weeks later, the boy's parents take him to the ER at the local hospital because he continues to have fever and noticeable pain in his leg. This time, x-rays show definite osteomyelitis and the boy is admitted to the hospital and started on intravenous antibiotic therapy. Unfortunately, the osteomyelitis has progressed to the chronic phase, where the reduced blood supply has resulted in the formation of sequestra. (In a case like this, the blood supply is disrupted by the pressure on the blood vessels that is caused by local inflammation.) The chance of successful treatment is decreased significantly by the delay in diagnosis so, over the next few years, the patient experiences a slowly progressive infection with a number of acute flare-ups each year. He spends many days in the hospital and undergoes multiple surgeries to drain pus and remove infected dead bone tissue. In addition, he experiences several fractures because the bone is severely weakened. After about 10 years, it becomes necessary to amputate his leg in order to keep the infection from spreading to the hip joint and pelvis.