Bacteria can colonize the bone either directly through soft tissue trauma or indirectly through hematogenous dissemination. In pediatric patients, the majority of acute osteomyelitis arises from hematogenous dissemination.
The incidence of acute osteomyelitis in children is in the range of 8 per 100,000 per year in developed countries, but the incidence of the disease is significantly higher in low-income countries. The incidence is about twice as high in male children compared to females. If acute osteomyelitis is not diagnosed and treated appropriately in a timely manner, it often induces catastrophic clinical consequences, which may lead to death in severe cases.
Staphylococcus aureus is by far the most common bacterium infecting acute osteomyelitis, followed by respiratory pathogens such as Streptococcus pyogenes and Streptococcus pneumoniae; Haemophilus influenzae type B often infects the joint cavity rather than the bone, for unknown reasons. Salmonella is more common in developing countries and in patients with acute osteomyelitis in sickle cell anemia. aureus infections are most common in children under 4 years of age and their incidence is increasing.
Clinical presentation
In patients diagnosed with osteomyelitis, the duration of the disease is less than 2 weeks for acute, 2 weeks-3 months for subacute, and more than 3 months for chronic. Because acute osteomyelitis can involve all parts of the body, its clinical signs and symptoms are variable. Multifocal acute osteomyelitis can occur at any age, but is more common in newborns.
The most common symptoms of acute osteomyelitis in children are claudication or difficulty walking, fever, local tenderness, and sometimes erythema localized to the osteomyelitis (Figure 1). In some patients with acute osteomyelitis, the disease deteriorates before the onset of clinical symptoms. The onset of heel osteomyelitis is insidious, and delays in diagnosis and treatment are likely to occur. Spinal osteomyelitis usually presents with back pain, and sacral osteomyelitis is suggested by the presence of pain in the sacral region on anal examination.
The diagnosis of acute osteomyelitis needs to be excluded in all patients with fever of unknown diagnostic origin. Acute osteomyelitis can occur at any age, but is more common in prepubertal boys, probably because these patients are usually more athletic and prone to microtrauma induced bacteria into the bloodstream. Patients with osteomyelitis infected with MRSA have high body temperature, rapid heart rate, and more severe lower extremity pain and claudication at the onset.
Figure 1: The distribution range and frequency of acute osteomyelitis in children within the whole body skeleton
Diagnosis
Figure 2 marks the clinical pathway for the diagnosis of a patient with acute osteomyelitis in children. If physical examination findings suggest lesion involvement of bone, further investigations are required. Serum CRP and calcitoninogen are more sensitive to disease monitoring during clinical diagnosis and later follow-up, but calcitoninogen monitoring is more expensive and is less used in the clinic than CRP.
If there is a sustained decrease in CRP values during monitoring, even if the patient’s temperature persists, this indicates that the treatment is effective. CRP, ESR, and white blood cell count are more elevated in osteomyelitis due to MRSA than in other types of pathogens.
Figure 2: Diagnosis and treatment strategies for acute osteomyelitis in children
The onset of osteomyelitis symptoms is 2-3 weeks before the rat-bite like appearance on X-ray. A normal radiograph at the patient’s initial presentation is not significantly helpful in excluding the diagnosis of osteomyelitis. Even so, X-rays can provide important diagnostic value in facilities that do not have advanced imaging facilities, as they can exclude other clinical conditions that may cause localized osteomyelitis, such as fractures and sarcomas.
MRI is a more sensitive and specific diagnostic method, but its equipment and examination costs are more expensive, and some institutions do not have MRI equipment, which limits its clinical application.
It is important to identify the pathogenic organisms of acute osteomyelitis before proceeding with treatment. Methods to obtain the pathogenic bacteria include: puncture and drainage fluid from the site of osteomyelitis, specimens obtained by debridement, and blood tests. It has been recommended that blood cultures be routinely performed in patients with osteomyelitis to identify the type of osteomyelitis pathogen, but it should be noted that a negative blood culture or culture of pus from the puncture site does not exclude osteomyelitis infection, as the above tests have only a 40-70% positive rate.
Treatment
Antibiotic therapy
All antibiotic choices are based on the clinician’s experience until clear information is available about the bacteria infecting osteomyelitis and their drug resistance. The most common types of antibiotics currently used are summarized in Table 1.
When treating with oral formulations of antibiotics, attention needs to be paid to their side effects, as oral antibiotic doses tend to be higher. The antibiotic of choice should readily penetrate and be absorbed by the bone tissue. Time-dependent short blood half-life antibiotics require a high frequency of administration. Clindamycin and first-generation cephalosporins meet these requirements.
Some reports in the literature suggest that monotherapy with antibiotics for acute osteomyelitis can achieve good therapeutic results and, furthermore, that their side effects are within acceptable limits when applied in high doses. Anti-staphylococcal penicillin is effective in the treatment of osteomyelitis and has an adequate safety profile.
Clindamycin is less likely to have diarrheal effects in children, but skin erythema sometimes occurs. Most MRSA are also sensitive to clindamycin. Clindamycin is not clinically recommended for the treatment of Staphylococcus aureus, but rather for the treatment with beta-lactamase drugs. Streptococcus pyogenes or Streptococcus pneumoniae, for example, can also be treated with beta-lactamase analogues.
The less common infecting bacteria Haemophilus bleeding can be treated with ampicillin or amoxicillin if β-lactamase negative, or with second or third generation antibiotics if β-lactam positive. Infection with the above-mentioned pathogens needs to be considered in children under 4 years of age who are not vaccinated against Haemophilus influenzae with complications of osteomyelitis and septic arthritis.
Vancomycin is recommended as a first-line agent for children with unstable general condition or in areas of widespread clindamycin resistance, and if vancomycin therapy is ineffective, a switch to linezolid may be considered. When using vancomycin, attention needs to be paid to the ability of the drug to penetrate bone tissue and the dose and frequency of administration needs to be determined accordingly to ensure adequate drug concentration at the site of the lesion. Osteomyelitis caused by Salmonella can be treated with third-generation cephalosporins, such as cefotaxime, ceftriaxone, etc., and fluoroquinolones.
Table 1: List of antibiotics used in clinical practice for the treatment of acute osteomyelitis in children
Other adjuvant drugs may be required for the treatment of acute osteomyelitis. For example, NSAIDs may be used to lower the patient’s body temperature and relieve pain. There is no clinical evidence to support the use of glucocorticoids in patients with acute osteomyelitis. Anticoagulants should be used in patients with combined lower extremity venous thrombosis or pulmonary thrombosis.
Time point for changing antibiotics from intravenous to oral
Because acute osteomyelitis usually induces serious clinical consequences, possibly to the point of death in severe cases, to reduce this possibility, intravenous antibiotics are clinically used early in the treatment of children with acute osteomyelitis and are switched to oral antibiotics as the child approaches recovery. However, few clinicians realized that oral sulfonamide antibiotics were effective in treating patients with acute osteomyelitis in the late 1930s.
The variety of antibiotics and their antimicrobial spectrum have evolved greatly in recent years, and their treatment strategy has changed significantly, with intravenous antibiotics for acute osteomyelitis becoming a clinical habit, but with reference to the antibiotic treatment strategy of decades ago, there are no adverse consequences of starting oral antibiotics early in treatment. The question is, where is the early point in time for early oral administration.
Three studies have now demonstrated that in patients with acute osteomyelitis, intravenous antibiotic use lasting less than 1 week does not significantly alter the clinical functional prognosis. A systematic review completed in the United Kingdom found reliable efficacy of short-term parenteral administration for uncomplicated osteomyelitis. The authors found no significant recurrence of late osteomyelitis in 131 immunocomplete children aged >3 months treated with intravenous therapy for 2-4 days, followed by a switch to oral therapy. However, this finding does not apply to patients with MRSA. A more conservative antibiotic treatment strategy may be relatively appropriate in areas where MRSA infection is more severe, such as the United States, but further clarification from later clinical studies is needed.
Acute osteomyelitis course and treatment of refractory pathogens
In a study completed in 1960, a delay in starting treatment and a course of antibiotic use of less than 3 weeks were found to be risk factors for recurrence of osteomyelitis, but other related studies have concluded that antibiotic treatment cycles greater than 3 weeks do not significantly improve the level of patient benefit. A study completed in the United Kingdom concluded that cloxacillin used for 5 weeks could treat osteomyelitis and became the standard treatment strategy for decades thereafter.
In a study completed by the authors, a 20- or 30-day course of clindamycin or first-generation cephalosporins for osteomyelitis of MRSA, streptococcus or pneumococcus was found to be associated with shorter hospitalization periods, fewer side effects and better medical expenditures for short courses of oral therapy; in addition, there was less likelihood of bacterial resistance.
The Infectious Diseases Society of America recommends individualized treatment for all patients based on available evidence of clinical practice, and a minimum 4-6 week antibiotic regimen may be considered if the child’s acute osteomyelitis is caused by MRSA. However, it is important to note that there is a lack of strong evidence to support the above recommended measures. This treatment strategy may also be used in children with severe complications or osteomyelitis caused by Salmonella.
A specific type of MRSA can cause pathological fractures, but these fractures do not necessarily require surgical intervention. Compared to MSSA, MRSA is more likely to have complications related to deep vein thrombosis and septic pulmonary embolism. Methicillin-resistant streptococcal osteomyelitis has a higher rate of complications, whereas penicillin-resistant Streptococcus pneumoniae does not have an increased rate of complications.
Patients with osteomyelitis also have more specific conditions, such as patients who are neonates, immunosuppressed, and malnourished, and the duration of antibiotic therapy can be extended accordingly.
Application of surgical treatment
The key questions of when to surgically intervene, the extent of surgical debridement, and whether surgical intervention is necessary are not currently supported by clear clinical evidence. For patients with early osteomyelitis diagnosed in time, the efficiency of conservative treatment with drugs alone can reach more than 90%. In a study of 68 patients with early osteomyelitis treated with aggressive debridement, 17% developed chronic osteomyelitis after surgery.
An observational study prior to the use of antibiotics in the clinic found that patients with osteomyelitis who had early debridement had higher mortality but lower late complications, whereas osteomyelitis debridement delayed by one week or more had lower mortality but higher late complications. From the current evidence, early and extensive debridement of osteomyelitis does more harm than good, so simple drilling and drainage at the time of surgery is sufficient.
Once the patient is generally stable, or if the patient does not respond to medication within a few days, surgical drainage of the abscess bore may be considered to expedite disease healing. Aggressive surgical debridement is recommended for osteomyelitis caused by MRSA pathogenic infections, but it is important to emphasize that more evidence is needed at a later stage to support these recommendations. Surgical treatment of intramedullary abscesses due to subacute or chronic osteomyelitis is usually recommended.