Acute Osteomyelitis (Paediatric)

1. Clinical Overview

Summary

Acute Haematogenous Osteomyelitis (AHO) is a bacterial infection of the bone marrow, primarily affecting the rapidly growing metaphyses of long bones in children. It represents one of the most important paediatric orthopaedic emergencies, with an annual incidence of 2-13 per 100,000 children. [1,2] The pathophysiology centers on sluggish blood flow in the metaphyseal venous sinusoids, creating an environment where bacteria can settle and proliferate following transient bacteraemia.

The most common pathogen is Staphylococcus aureus, accounting for 70-90% of culture-positive cases, though Kingella kingae is increasingly recognised as a major pathogen in children under 4 years, particularly with modern molecular diagnostic techniques. [3,4] Clinically, AHO presents with the classic triad of fever, localised bone pain, and functional impairment (refusal to weight-bear or "pseudoparalysis" in infants).

The diagnostic challenge lies in the temporal gap between symptom onset and radiographic findings: conventional X-rays remain normal for 10-14 days until significant bone mineral loss occurs. [5] MRI with contrast has emerged as the gold standard for early diagnosis, demonstrating bone marrow oedema with sensitivity approaching 90-100%. [6] Treatment involves prolonged antibiotic therapy, with landmark evidence from the OVIVA trial demonstrating non-inferiority of early oral transition compared to prolonged intravenous therapy. [7] Surgical decompression is reserved for abscess formation or failure of medical management within 24-48 hours.

Key Facts

• Definition: Bacterial infection of the bone marrow and cortex, typically haematogenous in origin.
• Incidence: 2-13 per 100,000 children annually; higher in developing nations. [1]
• Age Distribution: Bimodal peak - infants less than 1 year and children 5-7 years.
• Site Predilection: Metaphysis of long bones (distal femur 40%, proximal tibia 30%, proximal humerus 10%). [2]
• Primary Pathogen: Staphylococcus aureus (70-90% of culture-positive cases). [3]
• Imaging Evolution: X-ray normal for 10-14 days; MRI sensitive from 24-48 hours. [5,6]
• Mortality: less than 1% in developed countries with prompt treatment; higher with MRSA or neonatal disease. [8]

Clinical Pearls

"X-rays are useless early": Do not be falsely reassured by a normal X-ray in the first 10-14 days. Radiographic changes (periosteal reaction, lytic lesions) require 50% bone mineral loss to be visible. A normal X-ray in a febrile, limping child with point tenderness does NOT exclude osteomyelitis. MRI or clinical diagnosis is essential. [5]

"Pseudoparalysis": In neonates and pre-verbal infants, the presenting complaint is often "not moving the limb" rather than pain. The affected limb appears flaccid but elicits pain on passive movement. This presentation is shared with fractures, septic arthritis, and brachial plexus injuries—require high index of suspicion. [9]

"The Four Intra-capsular Metaphyses": In most bones, the growth plate (physis) acts as a barrier preventing metaphyseal infection from spreading to the joint. However, in the Hip, Shoulder, Ankle (talus), and Elbow (radial head), the metaphysis lies within the joint capsule. Osteomyelitis at these sites can directly decompress into the joint, causing concomitant Septic Arthritis—a surgical emergency. [10]

"Kingella is the great mimicker": Kingella kingae causes a milder syndrome than S. aureus—lower fever, less elevated inflammatory markers, and culture-negative in 30-50% of cases using traditional methods. PCR-based detection is revolutionising diagnosis in toddlers with "culture-negative" osteoarticular infections. [4]

"Puncture through a Sneaker": A child who steps on a nail through rubber-soled footwear is at specific risk for Pseudomonas aeruginosa osteomyelitis (the organism colonises rubber). Empiric coverage must include anti-pseudomonal agents (ciprofloxacin or ceftazidime). [11]

"The 24-hour rule": Clinical improvement (defervescence, reduced pain) should be evident within 24-48 hours of appropriate antibiotic therapy. Persistent fever or toxicity beyond this window mandates imaging reassessment and consideration of surgical drainage. [1,2]

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2. Epidemiology and Risk Factors

Demographics

• Incidence:
  • Developed countries: 2-8 per 100,000 children per year. [1]
  • Developing countries: Up to 13 per 100,000, related to healthcare access and malnutrition. [2]
• Age Distribution:
  • Peak incidence: 5-7 years (maximal bone growth rate).
  • Second peak: Infancy (less than 1 year), often more severe with multi-focal involvement. [9]
• Gender: Male predominance (2:1), possibly related to higher trauma rates seeding bacteraemia. [1]
• Seasonality: Slight winter predominance, correlating with respiratory viral infections that may predispose to bacteraemia.

Host Risk Factors

Microbiology: The Pathogen Landscape

The MRSA Epidemic

Methicillin-resistant S. aureus (MRSA) prevalence varies dramatically by geography: 2-5% in Northern Europe, 10-20% in UK, 30-40% in USA (community-acquired strains). [3] MRSA osteomyelitis is associated with:

• Longer hospital stays (median 7 vs 4 days).
• Higher surgical intervention rates (50% vs 30%).
• Increased risk of chronic osteomyelitis and treatment failure.
• Panton-Valentine Leukocidin (PVL) toxin production causing tissue necrosis.

Risk factors for MRSA include: recent hospitalisation, contact sports (wrestling), skin infections, IV drug use (adolescents), and endemic community strains.

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3. Pathophysiology: From Bacteraemia to Bone Destruction

The Vascular Anatomy of the Metaphysis

The metaphysis is uniquely vulnerable due to its vascular architecture:

1. Nutrient Artery Entry: The nutrient artery penetrates the diaphyseal cortex and ascends/descends into the medullary canal.
2. Metaphyseal Arterial Loops: Near the growth plate, arteries form sharp hairpin loops, transitioning to large-calibre venous sinusoids.
3. Sluggish Flow: Blood flow velocity decreases dramatically in these sinusoids (from 2-3 mm/s in arterioles to less than 0.5 mm/s), creating turbulence.
4. Fenestrated Endothelium: The sinusoidal endothelium is discontinuous, lacking basement membrane in places, facilitating bacterial extravasation.
5. Phagocyte Paucity: The metaphyseal region has relatively few resident macrophages compared to the diaphysis or epiphysis. [13]

Bacterial Seeding and Establishment

Transient bacteraemia is common in childhood (tooth brushing, minor abrasions, viral upper respiratory tract infections [URTIs]). In healthy children, circulating bacteria are rapidly cleared by reticuloendothelial system. Osteomyelitis develops when:

1. High Inoculum: Intense or prolonged bacteraemia (e.g., from occult skin infection).
2. Bacterial Virulence Factors:
   • S. aureus produces fibronectin-binding proteins (FnBPA, FnBPB) that adhere to exposed bone matrix.
   • Protein A binds to endothelium.
   • Biofilm formation on bone surfaces resists antibiotic penetration and phagocytosis. [14]
3. Metaphyseal Microtrauma: Minor blunt trauma creates microhaematomas, providing a fibrin scaffold for bacterial adherence.

The Inflammatory Cascade

Once bacteria establish in the metaphysis:

Hours 0-24:

• Bacterial proliferation within the intertrabecular spaces of the metaphysis.
• Activation of innate immunity: neutrophil recruitment, complement activation, cytokine release (IL-1β, TNF-α, IL-6).

Days 1-3:

• Abscess Formation: Pus accumulates under pressure within the rigid bony compartment.
• Venous Thrombosis: Inflammatory mediators cause thrombosis of metaphyseal venous sinusoids, leading to bone ischaemia and necrosis.
• Cortical Breach: Pus tracks through Haversian canals and Volkmann canals to reach the periosteum.

Days 3-7:

• Subperiosteal Abscess: Pus lifts the periosteum off the cortex, stripping it of blood supply (periosteal arteries provide outer 1/3 of cortical blood flow). This causes further cortical necrosis.
• Periosteal Reaction: The elevated periosteum lays down new bone (involucrum) visible on X-ray after 10-14 days.

Weeks 2-4 (if untreated):

• Sequestrum Formation: Devascularised bone dies and becomes a sequestrum—a free fragment of necrotic bone sitting in a pool of pus. Antibiotics cannot penetrate sequestra (no blood supply), and they act as a foreign body, perpetuating infection.
• Involucrum: New periosteal bone forms around the infection, creating a shell. Pus drains through cloaca (defects in the involucrum).
• Chronic Osteomyelitis: Established.

Age-Specific Pathophysiology

Neonates (less than 1 year)

• Trans-physeal Vessels: In infants, blood vessels cross the growth plate, connecting metaphysis and epiphysis. [9]
• Consequences:
  • Infection spreads across the physis into the epiphysis, damaging the growth plate and causing growth arrest.
  • Higher rate of septic arthritis (50-70% in neonates vs 10-20% in older children).
  • Multifocal involvement in 30-40% (haematogenous seeding to multiple bones).

Children (1-16 years)

• Physis as Barrier: The growth plate is avascular and acts as a barrier. Infection is typically confined to the metaphysis unless intracapsular (hip/shoulder/ankle/elbow).
• Subperiosteal Spread: Primary route is lateral through cortex to subperiosteal space.

Adolescents (Post-physeal Closure)

• Physeal Closure: After skeletal maturity, vessels reestablish across the fused physis.
• Epiphyseal Involvement: Infection can spread to epiphysis and joint, resembling adult osteomyelitis.

Pathophysiology of Chronic Osteomyelitis

If acute osteomyelitis is inadequately treated:

• Biofilm Formation: Bacteria within sequestra and on necrotic bone form biofilms, which are 100-1000x more resistant to antibiotics.
• Persistent Inflammation: Low-grade infection causes ongoing bone destruction and formation.
• Brodie's Abscess: A specific form—well-circumscribed abscess within the metaphysis, surrounded by sclerotic bone, presenting as chronic pain without systemic features. [15]

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4. Clinical Presentation: Recognising the Spectrum

Symptoms: The Classic Triad

1. Fever: Present in 60-90% at presentation. [1,2]

   • Temperature typically > 38.5°C.
   • May be absent in neonates or Kingella infection.
   • Persistent fever > 48 hours on antibiotics suggests abscess or resistant organism.

2. Bone Pain: Deep, constant, progressive.

   • Localised to the affected metaphysis.
   • Worse with movement or weight-bearing.
   • Night pain is characteristic (differentiates from transient synovitis).

3. Functional Impairment:

   • Lower Limb: Limp, refusal to weight-bear, antalgic gait.
   • Upper Limb: Not using the arm, holding it protectively.
   • Infant: Pseudoparalysis—flaccid limb with pain on passive movement. [9]

Physical Examination Findings

Inspection

• Swelling: Late sign (days 3-7), indicates subperiosteal extension.
• Erythema: Overlying skin may be warm and red (20-40% of cases).
• Posture: Limb held in position of comfort (hip flexed in hip osteomyelitis).

Palpation

• Point Tenderness: The hallmark sign. Exquisite, focal tenderness over the metaphysis—typically can localise to a 2cm circle ("finger-tip test"). [2]
• Warmth: Increased temperature over affected bone.
• Palpable Fluctuance: Rare; suggests large subperiosteal abscess.

Range of Motion (ROM)

• Key Discriminator:
  • "Osteomyelitis: ROM typically preserved (may have pain at extremes). Child can actively move the joint through range."
  • "Septic Arthritis: ROM severely restricted; child refuses active or passive movement. [10]"
• Exception: Intracapsular metaphyses (hip/shoulder) with joint involvement.

Special Tests

• Percussion Test: Gentle percussion of the bone (e.g., tapping heel in tibial osteomyelitis) elicits pain at the infected site.
• Passive Stretch: Stretching muscles attached to the infected bone causes pain (e.g., passive dorsiflexion in calcaneal osteomyelitis).

Clinical Syndromes

Acute Osteomyelitis (Classic)

• Duration: less than 2 weeks.
• Presentation: Acute systemic illness, high fever, localised pain.
• Organism: S. aureus, Group A Strep.

Subacute Osteomyelitis

• Duration: 2-12 weeks.
• Presentation: Mild or no fever, chronic pain, subtle limp.
• Organism: Kingella, less virulent S. aureus strains.
• Imaging: Lytic lesion with surrounding sclerosis (Brodie's abscess pattern). [15]

Chronic Osteomyelitis

• Duration: > 12 weeks or recurrent.
• Presentation: Recurrent pain, draining sinus, exacerbations and remissions.
• Pathology: Sequestrum, involucrum, cloaca.
• Treatment: Requires surgical debridement.

Neonatal Osteomyelitis

• Age: 0-3 months.
• Presentation: Often subtle—irritability, poor feeding, pseudoparalysis. Fever in only 40-50%. [9]
• Complications: Multifocal (30-40%), septic arthritis (50-70%), growth arrest (20-30%).
• Organisms: S. aureus, Group B Streptococcus, Gram-negative bacilli (E. coli, Klebsiella).

Differential Diagnosis: Mimics and Overlaps

Kocher Criteria for Septic Arthritis vs Transient Synovitis (Hip)

Each criterion = 1 point: [16]

1. Fever > 38.5°C
2. Non-weight bearing
3. ESR > 40 mm/hr
4. WCC > 12,000 cells/μL

Probability of Septic Arthritis: 0 criteria = 2%; 1 = 9%; 2 = 35%; 3 = 73%; 4 = 93%.

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5. Investigations: Confirming the Diagnosis

Blood Tests

Inflammatory Markers

Clinical Application:

• CRP > 20 mg/L + clinical features → strong suspicion for osteomyelitis. [19]
• CRP less than 20 mg/L + afebrile + well-appearing → consider transient synovitis, subacute infection, or Kingella.
• Trend more important than absolute value: Failure of CRP to halve within 48-72 hours of antibiotics suggests treatment failure or abscess.

Blood Cultures

• Yield: 30-50% positive in acute osteomyelitis. [1,3]
• Timing: MUST be taken before antibiotics.
• Technique: Two sets (aerobic and anaerobic bottles) from separate venepuncture sites.
• Volume: Paediatric bottles; at least 1-3 mL blood per bottle (yield increases with volume).
• Importance: Identify organism and guide targeted therapy; resistance patterns (MRSA).

Additional Blood Tests

• FBC: May show leucocytosis, but normal in > 50% of cases.
• Blood Film: Essential if malignancy suspected (blasts in ALL).
• U&E, LFTs: Baseline for antibiotic monitoring (vancomycin nephrotoxicity, clindamycin hepatotoxicity).
• Sickle Screen: In at-risk populations (African, Mediterranean ancestry).

Imaging: The Diagnostic Pathway

X-Ray (Plain Radiography)

Role: Initial imaging; exclude fracture or malignancy; monitor chronic disease.

Timing of Radiographic Changes: [5]

• Days 0-7: Normal bone. Soft tissue swelling only (displacement of fat planes).
• Days 10-14: Periosteal reaction (lifting of periosteum creates new bone).
• Days 14-21: Lytic destruction (moth-eaten appearance).
• Weeks 4-6: Sequestrum (dense bone fragment) and involucrum (new bone shell).

Sensitivity: less than 50% in first 2 weeks; 70-80% after 2 weeks.

Key Signs:

• Soft Tissue Swelling: Earliest sign (displacement of deep muscle planes).
• Periosteal Reaction: Linear new bone paralleling the cortex ("onion-skin" in layers; "sunburst" if perpendicular).
• Lytic Lesions: Focal bone destruction.

When to Use: All cases at presentation (exclude fracture); follow-up at 4-6 weeks to assess healing.

MRI (Magnetic Resonance Imaging)

Gold Standard for Diagnosis. [6]

Sensitivity: 90-100% from 24-48 hours post-symptom onset. Specificity: 85-95% (can have false positives with trauma, tumour, infarction).

Protocol:

• Sequences: T1-weighted, T2-weighted, STIR (Short Tau Inversion Recovery), T1 with gadolinium contrast.
• Coverage: Entire affected bone + adjacent joint.

MRI Findings:

Specific Signs:

• Bone Marrow Oedema: Diffuse T2 hyperintensity in metaphysis.
• Abscess: Focal fluid collection with rim enhancement (differentiates from sterile oedema or infarction).
• Subperiosteal Abscess: Fluid lifting periosteum off cortex.
• Soft Tissue Involvement: Myositis, cellulitis.
• Joint Effusion: Suggests concomitant septic arthritis (intracapsular sites).
• Physeal Changes: Disruption or enhancement of growth plate (neonatal disease).

Limitations:

• Requires general anaesthesia in young children.
• Contraindications: Pacemakers, cochlear implants, metallic foreign bodies.
• Cost and availability.

When to Use: High clinical suspicion + normal X-ray; define extent before surgery; differentiate from tumour.

Ultrasound (US)

Role: Detect subperiosteal fluid; guide aspiration; detect joint effusion.

Findings:

• Subperiosteal Collection: Anechoic or hypoechoic fluid lifting periosteum.
• Soft Tissue Oedema: Increased echogenicity of muscles.
• Joint Effusion: In intracapsular sites.

Advantages: Bedside, no sedation, dynamic (real-time), radiation-free. Limitations: Operator-dependent; cannot visualise bone marrow (cortical bone blocks sound).

When to Use: Suspected subperiosteal abscess; guide needle aspiration; hip effusion (Kocher criteria).

CT (Computed Tomography)

Role: Chronic osteomyelitis; surgical planning; cortical sequestra.

Advantages:

• Excellent cortical bone detail.
• Identify sequestrum (density >normal bone due to lack of remodelling).
• Define cloaca and involucrum in chronic disease.

Disadvantages: Radiation exposure; poor soft tissue contrast vs MRI.

When to Use: Chronic osteomyelitis pre-operative planning; MRI contraindicated; spine involvement (CT-guided biopsy).

Nuclear Medicine (Bone Scintigraphy)

Technique: Technetium-99m MDP (methylene diphosphonate) concentrates in areas of increased bone turnover.

Phases:

1. Immediate (Blood Pool): Increased vascularity.
2. Delayed (3-4 hours): Increased osteoblast activity.

Findings: "Hot spot" of increased uptake in infected bone.

Sensitivity: 80-90% (less than MRI). Advantages: Whole-body scan (detects multifocal disease); useful if multiple sites suspected. Disadvantages: Radiation; low specificity (fracture, tumour, infarction also "hot"); less anatomical detail.

When to Use: Multifocal osteomyelitis (e.g., neonates); sickle cell disease (multiple infarcts + infection); spine osteomyelitis.

Microbiological Sampling

Bone Aspiration / Biopsy

Indications:

• Culture-negative blood cultures in ill child.
• Suspected atypical organism (TB, fungi).
• Chronic osteomyelitis.
• No response to empiric antibiotics.
• Uncertainty between infection and malignancy.

Technique:

• Percutaneous Aspiration: Under sedation/GA; fluoroscopy or ultrasound-guided.
• Open Biopsy: During surgical drainage.
• Samples: Send for:
  • "Microscopy: Gram stain."
  • "Culture: Aerobic, anaerobic, prolonged incubation (7-14 days for Kingella)."
  • "PCR: Kingella, MRSA, Mycobacterium."
  • "Histopathology: Exclude malignancy; identify chronic changes."

Yield: 50-70% positive (higher than blood cultures). [1,20]

Antibiotic Timing: Ideally pre-antibiotics, but DO NOT DELAY antibiotics in septic child for bone biopsy. Bacteria may still be cultured 48-72 hours into therapy.

Synovial Fluid Aspiration (if Joint Involved)

Indications: Clinical septic arthritis; ultrasound effusion in intracapsular sites (hip/shoulder).

Interpretation:

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6. Management: The Evidence-Based Approach

Initial Assessment and Resuscitation

All children with suspected osteomyelitis require hospital admission.

ABCDE Assessment

1. Airway/Breathing: Usually normal unless septic shock.
2. Circulation:
   • Tachycardia (fever vs hypovolaemia vs sepsis).
   • Capillary refill time, blood pressure.
   • Septic Shock: Rare but catastrophic (Panton-Valentine Leukocidin MRSA, Group A Strep). Requires ICU, inotropes, aggressive source control.
3. Disability: Neurovascular examination of affected limb (compartment syndrome risk with extensive soft tissue involvement).
4. Exposure: Examine entire skeleton (multifocal disease in 5-10%).

Baseline Investigations (Pre-Antibiotic)

• Blood cultures ×2.
• FBC, CRP, ESR, U&E, LFTs, blood glucose.
• X-ray of affected bone (two views).
• Consider: Sickle screen, HIV test (if risk factors).

Fluid Resuscitation

• Bolus 10-20 mL/kg 0.9% saline if signs of dehydration or shock.
• Maintenance fluids.

Analgesia

• WHO Pain Ladder:
  • "Mild: Paracetamol 15 mg/kg PO/IV 6-hourly."
  • "Moderate: Ibuprofen 10 mg/kg PO 8-hourly (avoid if renal impairment)."
  • "Severe: Morphine 0.05-0.1 mg/kg IV/SC 4-hourly or PCA (patient-controlled analgesia) in older children."
• Immobilisation: Splint or cast for comfort and prevention of pathological fracture.

Antibiotic Therapy: The OVIVA Revolution

Empiric Antibiotic Choice

Start empiric antibiotics immediately after blood cultures (within 1 hour of presentation in septic child). [1,2]

Standard Empiric Regimen (MSSA suspected):

• Flucloxacillin 50 mg/kg IV 6-hourly (max 2g per dose)
  • OR Cefazolin 50 mg/kg IV 8-hourly (max 2g per dose)
  • Covers S. aureus, Group A Strep.

MRSA Risk Factors Present (recent hospitalisation, endemic area, PVL toxin syndrome):

• Vancomycin 15 mg/kg IV 8-12 hourly (target trough 10-20 mg/L)
  • OR Linezolid 10 mg/kg IV/PO 8-hourly (max 600mg per dose)
  • PLUS Flucloxacillin (cover MSSA until culture results).

Neonates (0-3 months):

• Flucloxacillin 50 mg/kg IV 6-hourly
  • PLUS Gentamicin 4-7 mg/kg IV once daily (covers Gram-negative bacilli, E. coli, Klebsiella).

Sickle Cell Disease:

• Ceftriaxone 80 mg/kg IV once daily (max 4g) (covers Salmonella, S. aureus)
  • OR Ciprofloxacin 10 mg/kg IV 12-hourly (if older child).

Puncture Wound (Pseudomonas Risk):

• Ceftazidime 50 mg/kg IV 8-hourly (max 6g/day)
  • OR Piperacillin-tazobactam 100 mg/kg IV 8-hourly (max 4.5g per dose)
  • OR Ciprofloxacin 10 mg/kg IV 12-hourly (if > 1 year).

Targeted Antibiotic Therapy (Once Culture Results Available)

The OVIVA Trial: Paradigm Shift

Landmark RCT (Li et al., NEJM 2019): [7]

• Population: 1054 adults and children with bone/joint infections.
• Intervention: Early oral switch (within 7 days) vs prolonged IV antibiotics (≥6 weeks IV).
• Outcome: Non-inferiority for definitive treatment failure at 1 year (oral 14% vs IV 13%; difference 0.8%, 95% CI -2.2% to 4.0%).
• Implication: Early oral switch is safe and non-inferior once child is clinically improving (afebrile, CRP declining).

Modern Practice (Post-OVIVA):

1. Initial IV therapy: Until clinical improvement (usually 3-7 days):
   • Afebrile for > 24 hours.
   • Improved pain and mobility.
   • CRP declining (50% reduction from peak).
2. Switch to oral therapy: High bioavailability agents:
   • Flucloxacillin 25-50 mg/kg PO QDS.
   • Linezolid 10 mg/kg PO TDS (MRSA).
   • Clindamycin 10 mg/kg PO TDS (if intolerant to flucloxacillin; NOT for Kingella).
   • Ciprofloxacin 15-20 mg/kg PO BD (Pseudomonas, Salmonella).
3. Total duration: 3-4 weeks for uncomplicated cases; 6 weeks for complicated (abscess, chronic, MRSA).

Monitoring on Oral Therapy:

• Weekly CRP (should normalise by 3-4 weeks).
• Clinical review at 1, 2, 4 weeks.
• FBC, LFTs if prolonged therapy.

Antibiotic Failure

Definition: Persistent fever or worsening symptoms after 48 hours of appropriate antibiotics. [1,2]

Causes:

1. Abscess Formation: Requires surgical drainage.
2. Resistant Organism: MRSA on flucloxacillin; review cultures.
3. Wrong Diagnosis: Malignancy, CRMO, fungal infection.
4. Inadequate Dosing: Check levels (vancomycin trough less than 10 mg/L).
5. Deep Vein Thrombosis: Complication causing persistent fever.

Management:

• Repeat blood cultures.
• MRI: Assess for abscess, extent.
• Escalate antibiotics: Add MRSA cover if not already on.
• Surgical Drainage: If abscess > 2cm or extensive subperiosteal collection.

Surgical Management

Indications for Surgery

1. Subperiosteal or Intraosseous Abscess: Pus collection > 2cm on MRI. [1,20]
2. Clinical Failure: No improvement after 48-72 hours of appropriate antibiotics.
3. Septic Arthritis (Intracapsular Sites): Joint washout indicated.
4. Chronic Osteomyelitis: Sequestrum or sinus tract requiring debridement.
5. Diagnostic Uncertainty: Biopsy to exclude malignancy.

Surgical Procedures

1. Drill Hole Decompression (Cortical Window):

• Technique: Under GA, fluoroscopy guidance, 4-6mm drill hole through cortex into medullary canal at site of maximum tenderness/MRI abnormality.
• Purpose: Vent pus, reduce intramedullary pressure, obtain culture samples.
• Post-op: Copious irrigation; wound left open or loosely closed; immobilisation in splint.

2. Open Debridement and Washout:

• Indications: Extensive subperiosteal abscess, soft tissue involvement, chronic osteomyelitis.
• Technique: Longitudinal incision, elevate periosteum, remove pus and necrotic tissue, curettage of sequestra, high-volume irrigation (3-6 litres saline).
• Post-op: Drain insertion; IV antibiotics 7-14 days; wound closure or negative pressure dressing.

3. Sequestrectomy (Chronic Osteomyelitis):

• Technique: Remove dead bone fragment (sequestrum); curettage of involucrum; drill holes to improve vascularity.
• Adjuncts: Local antibiotic delivery (gentamicin-impregnated beads/cement).

Post-Operative Care

• Immobilisation: Splint for 2-4 weeks.
• Weight-bearing: Non-weight bearing lower limb until pain-free (usually 2-3 weeks).
• Physiotherapy: ROM exercises after acute pain settles.
• Antibiotics: Continue for 4-6 weeks post-surgery.

Supportive Management

• Thromboprophylaxis: Consider in adolescents with prolonged immobilisation (LMWH).
• Nutrition: High-calorie diet; supplements if malnourished.
• Psychological Support: Prolonged hospitalisation, painful procedures.
• School Liaison: Home tutoring during extended absence.

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7. Complications and Prognosis

Acute Complications (During Active Infection)

1. Septic Arthritis (10-30% in Intracapsular Sites)

• Mechanism: Direct spread from metaphyseal infection across capsule (hip, shoulder, ankle, elbow). [10]
• Presentation: Severe pain, inability to move joint, joint effusion on ultrasound.
• Management: Urgent arthrotomy or arthroscopic washout + IV antibiotics.
• Prognosis: Cartilage damage if delayed > 48 hours; risk of secondary osteoarthritis.

2. Septic Shock / Multi-Organ Dysfunction (1-5%)

• Organisms: MRSA with PVL toxin, Group A Strep (necrotising fasciitis). [3]
• Presentation: Hypotension, tachycardia, reduced urine output, altered consciousness.
• Management: PICU admission, inotropic support, aggressive source control (surgical drainage), broad-spectrum antibiotics.
• Mortality: 5-10% despite treatment.

3. Deep Vein Thrombosis (DVT) (5-10%)

• Mechanism: Local inflammation, venous stasis, immobilisation. [2]
• Presentation: Persistent fever despite antibiotics, swollen limb, positive D-dimer.
• Investigation: Doppler ultrasound.
• Management: Therapeutic LMWH (enoxaparin 1.5 mg/kg SC once daily) for 3 months.

4. Pathological Fracture (less than 5%)

• Mechanism: Cortical destruction weakens bone.
• Management: Internal fixation after infection controlled.

5. Compartment Syndrome (Rare)

• Mechanism: Extensive soft tissue infection causing muscle swelling in confined fascial compartment.
• Presentation: The 5 P's—Pain (disproportionate), Pressure, Paraesthesia, Pallor, Pulselessness (late).
• Management: Emergency fasciotomy.

Chronic Complications (Long-Term Sequelae)

1. Chronic Osteomyelitis (5-10%)

• Definition: Persistent or recurrent infection > 12 weeks, or healed acute infection with relapse. [15]
• Pathology: Sequestrum, involucrum, sinus tract.
• Presentation: Recurrent pain, swelling, draining sinus (pus ± bone fragments).
• Investigation: X-ray (sequestrum = dense bone fragment), CT (better cortical detail), MRI (active infection vs quiescent).
• Management: Surgical debridement (sequestrectomy), prolonged antibiotics (6-12 weeks), hyperbaric oxygen (adjunct).
• Prognosis: Recurrence rate 20-30%; may require multiple surgeries.

2. Growth Plate Arrest (Physeal Injury) (5-15% Neonates, less than 5% Older Children)

• Mechanism:
  • Direct infection crossing physis (neonates with trans-physeal vessels). [9]
  • Ischaemic damage from septic thrombosis of physeal vessels.
  • Iatrogenic from surgical drilling across physis.
• Types:
  • "Complete Arrest: Entire physis stops growing → limb length discrepancy."
  • "Partial Arrest: Focal physeal bar → angular deformity (varus/valgus)."
• Presentation: Detected on follow-up X-rays at 6-12 months (discrepancy in bone length or angular deformity).
• Management:
  • "Observation: If discrepancy less than 2cm at skeletal maturity (cosmetic only)."
  • "Epiphysiodesis (Contralateral Limb): Stop growth in normal limb to equalise lengths."
  • "Limb Lengthening: Ilizarov frame, distraction osteogenesis (if > 2cm discrepancy)."
  • "Physeal Bar Excision: If partial arrest and > 2 years growth remaining."
• Prognosis: Permanent discrepancy; psychosocial impact; functional limitation if > 4cm.

3. Avascular Necrosis (AVN) (Rare, less than 5%)

• Sites: Proximal femoral head (hip), talus, proximal humerus (tenuous blood supply).
• Mechanism: Septic thrombosis of arterial supply (lateral epiphyseal artery in hip).
• Presentation: Collapse of articular surface; secondary osteoarthritis by adolescence.
• Management: Salvage procedures (valgus osteotomy in childhood; total hip replacement post-skeletal maturity).

4. Recurrence (5-10%)

• Risk Factors: Inadequate antibiotic duration (less than 3 weeks), MRSA, biofilm formation, retained sequestrum.
• Management: Prolonged antibiotic course (6-12 weeks), surgical debridement.

Prognosis

Uncomplicated Acute Osteomyelitis (Majority)

• Cure Rate: > 95% with prompt diagnosis and appropriate antibiotics. [1,2]
• Time to Resolution:
  • "Fever settles: 24-48 hours."
  • "Pain improves: 3-5 days."
  • "Normalisation of CRP: 2-4 weeks."
  • "Full return to activity: 6-8 weeks."
• Long-Term Outcome: Normal bone structure and function; no restriction on sports/activities.

Poor Prognostic Factors

Follow-Up Schedule

• Week 1, 2, 4: Clinical review + CRP.
• 6-12 months: X-ray to assess bone healing and growth plate integrity.
• Annual Review (2-5 years): If physis at risk—monitor for length discrepancy, angular deformity.
• Discharge: At 2 years if normal bone structure, equal limb lengths, and no recurrence.

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8. Special Scenarios and Controversies

Kingella kingae: The Great Mimicker

Kingella kingae is a fastidious Gram-negative coccobacillus colonising the oropharynx, transmitted via respiratory droplets in daycare settings. [4]

Why It Was Missed Historically:

• Requires enriched media (blood culture bottles, chocolate agar).
• Slow growth (3-7 days).
• Low bacterial load.
• Traditional culture: Positive in only 30-50% of cases.

Modern Diagnosis:

• PCR (16S rRNA gene): Detects Kingella DNA in synovial fluid or bone aspirate with 90-95% sensitivity. [4]
• Blood Culture Bottle Inoculation: Directly inoculating joint/bone aspirate into paediatric blood culture bottles increases yield to 70-80%.

Clinical Clues:

• Age 6 months to 4 years.
• Mild systemic illness (low-grade fever, well-appearing).
• Normal or mildly elevated WCC, CRP less than 50 mg/L.
• "Culture-negative" osteomyelitis.

Treatment:

• Amoxicillin 50 mg/kg PO TDS (90% susceptible).
• Cephalosporins (cefazolin, ceftriaxone).
• AVOID Clindamycin: Intrinsic resistance.

Prognosis: Excellent; low complication rate; early oral switch safe.

Neonatal Osteomyelitis: The Most Dangerous

Neonatal osteomyelitis (less than 3 months) is distinct and more severe: [9]

Unique Features:

1. Trans-Physeal Vessels: Blood vessels cross the growth plate, allowing infection to spread to epiphysis and joint.
2. Multifocal Disease: 30-40% have involvement of > 2 bones (haematogenous seeding).
3. Subtle Presentation: Fever in only 40-50%; pseudoparalysis, irritability, poor feeding.
4. Organisms: S. aureus (50%), Group B Streptococcus (30%), Gram-negative bacilli (E. coli, Klebsiella) (20%).
5. Complications:
   • Septic arthritis: 50-70%.
   • Growth arrest: 20-30%.
   • Mortality: 2-5% (sepsis).

Empiric Antibiotic:

• Flucloxacillin (MSSA) PLUS Gentamicin (Gram-negative cover).

Duration: 4-6 weeks IV (limited oral absorption in neonates).

Long-Term Monitoring: Annual X-rays until skeletal maturity to detect growth arrest.

MRSA Osteomyelitis: The Resistant Challenge

Community-acquired MRSA (CA-MRSA) strains carry the Panton-Valentine Leukocidin (PVL) toxin, causing tissue necrosis and severe disease. [3]

Risk Factors:

• Household contact with MRSA.
• Recent hospitalisation.
• Contact sports (wrestling).
• Endemic regions (USA 30-40%, UK 10-20%).

Clinical Features:

• More severe systemic illness.
• Higher rate of abscess formation (50% vs 30%).
• Necrotising pneumonia (if PVL toxin).

Treatment:

• Vancomycin: 15 mg/kg IV 8-12 hourly (target trough 15-20 mg/L).
• Linezolid: 10 mg/kg IV/PO 8-hourly (better bioavailability; oral switch easier).
• Alternative: Daptomycin, tigecycline (salvage).

Monitoring: Vancomycin trough levels (pre-4th dose); FBC (linezolid thrombocytopenia).

Duration: 6 weeks total (5-7 days IV, then oral linezolid).

Chronic Recurrent Multifocal Osteomyelitis (CRMO)

CRMO is a rare autoinflammatory condition mimicking bacterial osteomyelitis but sterile on culture. [18]

Features:

• Multifocal bone pain (clavicle, pelvis, vertebrae—unusual for bacterial).
• Relapsing-remitting course.
• Elevated CRP/ESR but culture-negative.
• MRI: Multifocal bone marrow oedema.
• Histology: Sterile chronic inflammation, plasma cells, fibrosis.

Diagnosis: Exclusion diagnosis—bone biopsy sterile; no response to antibiotics.

Treatment:

• NSAIDs: First-line (naproxen).
• Methotrexate: If NSAID-refractory.
• Anti-TNF Biologics: (Etanercept, infliximab) for severe disease.

Prognosis: Chronic; relapses common; rarely disabling.

Vertebral Osteomyelitis (Spondylodiscitis)

Infection of the vertebral body and intervertebral disc. [2]

Presentation:

• Back pain, refusal to walk, limp (referred from lumbar spine).
• Fever in 60%.
• Point tenderness over spinous process.
• Neurological deficit (10%): Cord compression emergency.

Investigation:

• MRI Spine: Gold standard—disc space T2 hyperintensity, endplate erosion, paravertebral abscess.
• CT-Guided Biopsy: If atypical (TB, fungi).

Organisms: S. aureus (60%), Kingella (20% in less than 4 years), TB (endemic areas).

Treatment:

• IV antibiotics 6-12 weeks (longer than appendicular osteomyelitis).
• Surgery: If neurological deficit (cord compression), abscess > 2cm, or instability.

Prognosis: Good with treatment; chronic pain in 10-20%.

Brodie's Abscess

A subacute osteomyelitis presenting as a well-circumscribed abscess within the metaphysis, surrounded by sclerotic bone. [15]

Presentation:

• Chronic pain (weeks to months).
• Minimal or no systemic features.
• X-ray: Lucent lesion with sclerotic rim (looks like a benign tumour).

Diagnosis: Biopsy to exclude osteoid osteoma, chondroblastoma, Langerhans cell histiocytosis.

Treatment: Curettage + antibiotics 3-4 weeks.

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9. Exam Viva Scenarios

Scenario 1: MRCP(CH) / MRCPCH Clinical

Stem: A 4-year-old boy presents with 3 days of fever (39°C), right thigh pain, and refusal to walk. X-ray femur is normal. CRP 85 mg/L. What is your differential diagnosis and management plan?

Model Answer: Differential:

1. Acute Osteomyelitis (most likely—fever, bone pain, elevated CRP).
2. Septic Arthritis (though would expect hip joint pain).
3. Transient Synovitis (less likely given high CRP).
4. Malignancy (leukaemia, Ewing sarcoma—chronic symptoms, night sweats).

Immediate Management:

• Admit.
• Blood cultures ×2 (before antibiotics).
• FBC, ESR, blood film.
• MRI femur (X-ray normal in first 10 days—MRI gold standard for early diagnosis).
• Start empiric IV flucloxacillin 50 mg/kg QDS (cover S. aureus).
• Analgesia (paracetamol, ibuprofen, consider morphine).
• Immobilise in Thomas splint.

Further Management:

• If MRI confirms osteomyelitis → continue antibiotics.
• Monitor fever, CRP (should improve in 48 hours).
• If no improvement at 48h → repeat MRI (assess for abscess), consider surgical drainage.
• Once afebrile and CRP declining → switch to oral flucloxacillin (OVIVA evidence).
• Total duration: 3-4 weeks.

Follow-Up:

• 6-month X-ray (assess growth plate if proximal femur).

Examiner Follow-Up: What if blood cultures grow MRSA? Answer: Switch to vancomycin IV (target trough 15-20 mg/L) or linezolid. Expect longer treatment (6 weeks), higher surgery rate (50% develop abscess). Monitor for complications (DVT, chronic osteomyelitis).

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Scenario 2: FRCS (Tr\u0026Orth) / FRACS Viva

Stem: A 6-month-old infant with a 2-day history of not moving the left leg. Febrile, CRP 110 mg/L. MRI shows distal femoral metaphyseal osteomyelitis with subperiosteal abscess. What are your concerns and management?

Model Answer: Concerns:

1. Intracapsular Metaphysis: Distal femur metaphysis is partially intracapsular → high risk of septic arthritis in knee joint.
2. Neonatal Age: Trans-physeal vessels cross growth plate → risk of epiphyseal involvement and growth arrest.
3. Subperiosteal Abscess: Requires surgical drainage.

Management:

1. Antibiotics:
   • Flucloxacillin 50 mg/kg IV QDS + Gentamicin 4-7 mg/kg IV OD (neonatal cover for Gram-negative bacilli).
2. Surgical Drainage:
   • Under GA, fluoroscopy.
   • Cortical window (drill metaphysis) + evacuate subperiosteal pus.
   • Washout, culture samples (bone + pus).
   • Leave drain, immobilise in splint.
3. Joint Assessment:
   • Ultrasound knee for effusion.
   • If effusion + clinical concern → arthrotomy knee washout.

Post-Op:

• Continue IV antibiotics 7-10 days, then switch to oral (if improving) to complete 4-6 weeks.
• Monitor CRP weekly.
• Long-Term: X-ray at 6, 12 months to assess for growth arrest (femoral length discrepancy). Counsel parents on risk of limb shortening, potential for future surgery (epiphysiodesis or lengthening).

Examiner: What is the risk of growth arrest in this case? Answer: 20-30% in neonates with metaphyseal osteomyelitis near physis, due to trans-physeal vascular spread. Higher risk with delayed treatment or extensive infection. Require annual scanograms until skeletal maturity.

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Scenario 3: MRCOG / FRANZCOG Neonatal Infection

Stem: A term neonate, day 10 of life, presents with irritability and reduced movement of the right arm. Mother had prolonged rupture of membranes. How do you approach this?

Model Answer: Differential:

1. Neonatal Osteomyelitis (proximal humerus).
2. Septic Arthritis (shoulder).
3. Brachial plexus injury (birth trauma—Erb's palsy).
4. Fracture (clavicle, humerus).

Assessment:

• Examination: Pseudoparalysis (limb flaccid, cries on movement). Moro reflex abnormal (unilateral).
• Bloods: FBC, CRP, blood cultures.
• Imaging: X-ray shoulder (exclude fracture). Ultrasound shoulder (effusion?). MRI if high suspicion (metaphyseal signal change).

Management (If Osteomyelitis Confirmed):

• Empiric Antibiotics: Flucloxacillin + Gentamicin (cover GBS, S. aureus, Gram-negatives).
• Multifocal Screening: Examine all limbs, spine (multifocal in 30-40% of neonatal osteomyelitis). Consider whole-body MRI or bone scintigraphy.
• Duration: IV antibiotics 4-6 weeks (neonates have poor oral absorption).
• Surgical Drainage: If abscess or septic arthritis.

Prognosis and Counselling:

• Explain to parents: Risk of growth arrest (20-30%), septic arthritis (50-70%), multifocal disease.
• Long-term follow-up: Annual X-rays to assess humeral length, shoulder development.

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10. Patient and Family Explanation

What is Osteomyelitis?

Osteomyelitis is an infection inside the bone, specifically in the bone marrow (the spongy part inside). It's similar to having a boil or abscess, but deep within the bone instead of on the skin. In your child's case, bacteria have travelled through the bloodstream and settled in the bone, where they've started multiplying and causing infection.

How Did My Child Get This?

Most cases happen when bacteria in the blood (from a minor cut, graze, or even brushing teeth) settle in the bone. Children's bones are growing rapidly, and the blood flow in certain parts of the bone is slower, which allows bacteria to "stick" and start growing. Sometimes, a recent minor bump or knock to the leg can create a small bruise inside the bone that attracts bacteria. It's important to know that this is not your fault—it's an unlucky event that can happen even in completely healthy children.

What Are the Symptoms?

• Fever (high temperature).
• Pain in the affected bone (thigh, shin, arm), which doesn't go away and gets worse.
• Refusal to use the limb—your child may not want to walk or move the arm.
• Tenderness—touching the area causes pain.

Why Isn't the X-Ray Showing Anything?

In the first 10-14 days of infection, X-rays look completely normal. This is because the bone needs to lose 50% of its mineral content before we can see changes on an X-ray. That's why we use an MRI scan, which is much more sensitive and can detect the infection within 1-2 days of symptoms starting.

Does My Child Need Surgery?

Most children don't need surgery if we catch the infection early. Antibiotics alone are usually enough. However, if the infection has formed a pocket of pus (an abscess) or if your child isn't getting better after 1-2 days of antibiotics, we may need to perform a small operation to drain the pus. This involves making a tiny hole in the bone to let the pressure out and wash away the infection.

How Long Will Treatment Take?

• Hospital stay: Usually 3-7 days (until the fever goes and the pain improves).
• Antibiotics: Start with intravenous (into the vein) antibiotics. Once your child is improving, we can switch to oral antibiotics (medicine by mouth) at home. Total treatment is usually 3-4 weeks.
• Follow-up: We'll see you in clinic at 1, 2, and 4 weeks to check blood tests and make sure the infection is clearing.

Will My Child's Bone Grow Normally?

In most cases, yes. The bone will heal completely, and your child will have no long-term problems. However, because the infection is near the growth plate (the part of the bone that makes children grow), there is a small risk (less than 5% in older children, higher in babies) that growth could be affected. We'll monitor this with X-rays over the next 6-12 months.

Can My Child Go Back to School/Sports?

• School: Once the fever has gone and your child is on oral antibiotics, they can return to school (usually 1-2 weeks).
• Sports: Your child should avoid contact sports and vigorous activity until the bone has fully healed (usually 6-8 weeks). Walking and gentle activity are fine once pain-free.

What Should I Watch For?

Contact us immediately if:

• Fever returns or doesn't go away.
• Pain gets worse.
• Swelling or redness increases.
• Your child stops taking the antibiotics.

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11. Technical Appendix: Classifications and Scoring

Cierny-Mader Classification (Adult Osteomyelitis)

Primarily used in adults but relevant for chronic paediatric cases:

Anatomic Type:

• Type 1: Medullary osteomyelitis (endosteum).
• Type 2: Superficial osteomyelitis (cortical surface).
• Type 3: Localised (full-thickness cortical + medullary, stable bone).
• Type 4: Diffuse (unstable bone, requires structural reconstruction).

Physiologic Host:

• A (Good): Normal immune system, good vascularity.
• B (Compromised): Systemic (diabetes, malnutrition) or local (chronic lymphoedema, venous stasis).
• C (Prohibitive): Treatment worse than disease (severe comorbidities).

Giedion Classification (Chronic Osteomyelitis Radiology)

• Type 1: Single sequestrum.
• Type 2: Multiple sequestra.
• Type 3: Diffuse sclerosis (Garre's sclerosing osteomyelitis).

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12. Evidence Base and Guidelines

Key Landmark Studies

1. Woods et al. (2021): PIDS/IDSA Guideline on Acute Hematogenous Osteomyelitis in Pediatrics. [1]

   • Comprehensive evidence-based guideline.
   • Recommendations: MRI preferred imaging; early oral switch acceptable; 3-4 weeks treatment for uncomplicated cases.

2. Li et al. (2019): OVIVA Trial—Oral vs IV Antibiotics for Bone and Joint Infection. [7]

   • Multicenter RCT, 1054 patients.
   • Result: Oral antibiotics non-inferior to IV after initial stabilization.
   • Impact: Changed practice globally; reduced hospitalization, improved quality of life.

3. Yagupsky et al. (2022): Kingella kingae Pathogenesis and Detection. [4]

   • Review of Kingella as major pathogen in osteoarticular infections in toddlers.
   • PCR-based detection essential.

4. Funk et al. (2017): Acute Hematogenous Osteomyelitis—Pathogenesis, Diagnosis, Treatment. [2]

   • Comprehensive review of metaphyseal vascular anatomy and pathophysiology.

5. Kocher et al. (1999): Differentiating Septic Arthritis from Transient Synovitis (Kocher Criteria). [16]

   • Predictive model using fever, non-weight bearing, ESR, WCC.
   • Validated in multiple studies; widely used.

Guideline Recommendations Summary

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13. References

1. Woods CR, Bradley JS, Chatterjee A, et al. Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics. J Pediatric Infect Dis Soc. 2021;10(8):801-844. doi:10.1093/jpids/piab027

2. Funk SS, Copley LAB. Acute Hematogenous Osteomyelitis in Children: Pathogenesis, Diagnosis, and Treatment. Orthop Clin North Am. 2017;48(2):199-208. doi:10.1016/j.ocl.2016.12.007

3. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin Infect Dis. 2011;52(3):e18-e55. doi:10.1093/cid/ciq146

4. Yagupsky P, Porsch EA, St Geme JW. Kingella kingae: an emerging pathogen in young children. Pediatrics. 2011;127(3):557-565. doi:10.1542/peds.2010-1867

5. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: a systematic review of the literature. J Bone Joint Surg Br. 2012;94-B(5):584-595. doi:10.1302/0301-620X.94B5.28523

6. Jaramillo D, Treves ST, Kasser JR, et al. Osteomyelitis and septic arthritis in children: appropriate use of imaging to guide treatment. AJR Am J Roentgenol. 1995;165(2):399-403. doi:10.2214/ajr.165.2.7618566

7. Li HK, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA). N Engl J Med. 2019;380(5):425-436. doi:10.1056/NEJMoa1710926

8. Krogstad P. Osteomyelitis. In: Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 8th ed. Elsevier; 2019:725-742.

9. Saavedra-Lozano J, Mejías A, Ahmad N, et al. Changing trends in acute osteomyelitis in children: impact of methicillin-resistant Staphylococcus aureus infections. J Pediatr Orthop. 2008;28(5):569-575. doi:10.1097/BPO.0b013e31817bb816

10. Pääkkönen M, Kallio MJT, Peltola H, Kallio PE. Sensitivity of erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res. 2010;468(3):861-866. doi:10.1007/s11999-009-0936-1

11. Fitzgerald RH, Cowan JDE. Puncture wounds of the foot. Orthop Clin North Am. 1975;6(4):965-972.

12. Ebong WW. Pathological fracture complicating long bone osteomyelitis in patients with sickle cell disease. J Pediatr Orthop. 1986;6(2):177-181. doi:10.1097/01241398-198603000-00010

13. Trueta J. The three types of acute haematogenous osteomyelitis: a clinical and vascular study. J Bone Joint Surg Br. 1959;41-B(4):671-680.

14. Lew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004;364(9431):369-379. doi:10.1016/S0140-6736(04)16727-5

15. Harris NH, Kirkaldy-Willis WH. Primary subacute pyogenic osteomyelitis. J Bone Joint Surg Br. 1965;47-B(3):526-532.

16. Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am. 1999;81(12):1662-1670. doi:10.2106/00004623-199912000-00002

17. Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology. 7th ed. Lippincott Williams \u0026 Wilkins; 2015.

18. Jansson AF, Müller TH, Gliera L, et al. Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheum. 2009;60(4):1152-1159. doi:10.1002/art.24402

19. Peltola H, Pääkkönen M, Kallio P, Kallio MJT. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Pediatr Infect Dis J. 2010;29(12):1123-1128. doi:10.1097/INF.0b013e3181f55a89

20. Gornitzky AL, Barker J, Bitterman A, et al. Diagnosis and Management of Osteomyelitis in Children: A Critical Analysis Review. JBJS Rev. 2020;8(9):e20.00095. doi:10.2106/JBJS.RVW.20.00095

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