OSTEOMYELITIS PATHOPHYSIOLOGY
Bacterial Bone Infection | Biofilm Formation | Chronic Sequestration
CIERNY-MADER CLASSIFICATION
Critical Must-Knows
- Staphylococcus aureus causes 80% of all osteomyelitis cases
- Biofilm formation on necrotic bone prevents antibiotic penetration
- Sequestrum = necrotic bone, Involucrum = new bone shell around infection
- Chronic osteomyelitis requires surgical debridement - antibiotics alone insufficient
- Australian eTG recommends flucloxacillin as first-line for MSSA osteomyelitis
Examiner's Pearls
- "Cierny-Mader combines anatomic location with host physiologic status
- "CRP more sensitive than ESR for monitoring treatment response
- "MRI has 90% sensitivity for osteomyelitis detection
- "Minimum 6 weeks total antibiotic therapy required for cure
Critical Osteomyelitis Exam Points
Pathophysiology
Biofilm formation is the key to chronicity. Bacteria adhere to necrotic bone in a glycocalyx matrix that prevents antibiotic and immune cell penetration. This is why surgery is mandatory for chronic osteomyelitis.
Classification
Cierny-Mader is the gold standard. Type I-IV describes anatomy, A-C describes host status. Type IV-C host (diffuse infection, compromised host) has worst prognosis.
Diagnosis
MRI is the investigation of choice - 90% sensitive, shows marrow oedema, abscess, and soft tissue extension. Plain XR takes 10-14 days to show changes. Always culture before antibiotics.
Treatment
Surgery plus antibiotics is synergistic. Debride all necrotic tissue, obtain cultures, dead space management, then 6 weeks antibiotics. Australian eTG: flucloxacillin first-line for MSSA.
At a Glance
Osteomyelitis is bacterial bone infection with Staphylococcus aureus responsible for 80% of cases. The key to chronicity is biofilm formation—bacteria adhere to necrotic bone within a glycocalyx matrix that prevents antibiotic and immune cell penetration. A sequestrum (necrotic bone fragment) acts as a nidus for persistent infection, while the involucrum (new bone shell) forms around the infected segment. The Cierny-Mader classification combines anatomic type (I-IV: medullary, superficial, localized, diffuse) with host status (A-C). MRI is the investigation of choice (90% sensitivity) showing marrow edema and abscess; plain X-ray changes take 10-14 days to appear. Treatment requires surgery plus antibiotics—debride all necrotic tissue, then 6 weeks antibiotics (Australian eTG: flucloxacillin first-line for MSSA). CRP is superior to ESR for monitoring response.
SPINSCommon Causative Organisms by Clinical Scenario
Memory Hook:When bacteria SPINS into bone, think of the clinical scenario to predict the organism!
CWEInflammatory Markers for Diagnosis and Monitoring
Memory Hook:CWE - CRP Wins Every time for monitoring osteomyelitis treatment response!
Overview/Introduction
Osteomyelitis is an infection of bone that can be caused by bacteria, fungi, or mycobacteria. The clinical presentation, microbiology, and management differ significantly between acute and chronic forms. Understanding the pathophysiology—particularly biofilm formation on necrotic bone—is fundamental to effective treatment.
Key Definitions:
- Sequestrum: Segment of necrotic, avascular bone that becomes colonized by bacteria and serves as a nidus for chronic infection
- Involucrum: Reactive new bone that forms around a sequestrum as the body attempts to wall off the infection
- Cloaca: Opening in the involucrum through which pus drains, often leading to a sinus tract
The fundamental principle is that chronic osteomyelitis cannot be cured with antibiotics alone—surgical debridement is mandatory because biofilm-coated sequestrum prevents antibiotic penetration.
Concepts and Mechanisms
Biofilm Formation - The Key to Chronicity
Biofilm is a structured community of bacteria enclosed in a self-produced polysaccharide matrix (glycocalyx). This matrix:
- Provides physical barrier against antibiotics
- Prevents neutrophil phagocytosis
- Allows bacteria to enter a dormant, metabolically inactive state
- Enables quorum sensing between bacteria
Bacteria within biofilm are 1000x more resistant to antibiotics than planktonic (free-floating) bacteria. This is the fundamental reason why surgical debridement—not antibiotics—is the cornerstone of chronic osteomyelitis treatment.
Vascular Anatomy and Susceptibility
Different bones have unique vascular patterns that influence infection susceptibility:
- Metaphysis of long bones: Sinusoidal blood flow with hairpin loops creates stagnant zones for bacterial seeding
- Vertebral bodies: Batson's valveless venous plexus allows retrograde seeding from pelvic/abdominal infections
- Cortical bone: Supplied by periosteal vessels—damage leads to avascular sequestrum formation
Host-Pathogen Interaction
The outcome of bone infection depends on the balance between bacterial virulence and host immune response. Local factors (vascular supply, foreign material) and systemic factors (diabetes, immunosuppression) determine whether infection resolves, becomes chronic, or disseminates.
Pathophysiology of Osteomyelitis
Routes of Infection
Haematogenous
- Metaphysis in children - slow sinusoidal blood flow
- Vertebral bodies in adults - Batson's plexus
- Bacteraemia seeds bone during transient episodes
- S. aureus most common organism
Contiguous Spread
- Post-surgical infection - hardware, fracture fixation
- Diabetic foot ulcers - direct inoculation
- Polymicrobial in trauma and diabetic cases
- Often involves soft tissue and bone together
Direct Inoculation
- Open fractures - contamination at injury
- Puncture wounds - nail through shoe (Pseudomonas)
- Combat injuries - high-energy trauma
- Implant surgery - low virulence organisms (Staph epidermidis)
Stages of Infection
Progression from Acute to Chronic
Bacterial invasion and inflammatory response. Vascular congestion leads to intraosseous pressure increase. Pus formation under periosteum causes subperiosteal abscess. Purulent material tracks along Volkmann canals.
Vascular compromise develops. Elevated intraosseous pressure compresses vessels causing ischaemia. Necrotic bone (sequestrum) forms. Body attempts to wall off infection with new bone shell (involucrum).
Biofilm formation on sequestrum. Bacteria enter dormant state within glycocalyx matrix. Sinus tracts form to skin. Recurrent flares despite antibiotics. Requires surgical debridement for cure.
Biofilm Significance
The biofilm is the fundamental problem in chronic osteomyelitis. Bacteria within the glycocalyx matrix are 1000x more resistant to antibiotics than planktonic forms. Biofilm also prevents neutrophil phagocytosis. This is why antibiotics alone cannot cure chronic osteomyelitis - surgical removal of the biofilm-colonized sequestrum is mandatory.
Microbiology
Organism by Patient Population and Site
| Patient Group | Site | Organism | Key Feature |
|---|---|---|---|
| Neonate under 4 months | Long bone metaphysis | Group B Streptococcus, E. coli | Crosses physis - can cause septic arthritis |
| Child 4 months to 4 years | Metaphysis of long bones | S. aureus, Kingella kingae | Metaphyseal vessels cross physis |
| Child over 4 years | Metaphysis | S. aureus 90% | Physis acts as barrier |
| Adult | Vertebral bodies | S. aureus, E. coli, Mycobacterium TB | Batson's plexus spread |
| Diabetic foot | Metatarsals, calcaneus | Polymicrobial, anaerobes, MRSA | Contiguous spread from ulcer |
| Sickle cell disease | Diaphysis, vertebrae | Salmonella > S. aureus | Only scenario where Salmonella more common |
| IV drug user | Vertebrae, long bones | S. aureus, Pseudomonas, Candida | Haematogenous seeding |
| Post-surgical implant | Fracture site | S. aureus, S. epidermidis, Propionibacterium | Low virulence biofilm formers |
Cierny-Mader Classification
Anatomic Classification (Type I-IV)
| Type | Location | Characteristics | Treatment |
|---|---|---|---|
| Type I - Medullary | Intramedullary canal | Endosteal surface, hematogenous | Reaming, antibiotics, nail |
| Type II - Superficial | Surface of bone | Exposed cortex, soft tissue loss | Debridement, flap coverage |
| Type III - Localized | Full thickness, stable | Cortical sequestrum, stable bone | Debride, maintain stability |
| Type IV - Diffuse | Permeative, unstable | Loss of structural integrity | Resection, bone transport, arthrodesis |
Type III vs Type IV Distinction
The key distinction: Type III leaves the bone stable after debridement (can just excise the localized infected segment). Type IV becomes unstable after debridement (requires reconstruction with bone transport, free fibula, or arthrodesis). This fundamentally changes the surgical plan.
Clinical Relevance and Diagnosis
Imaging Hierarchy
Plain Radiographs (first line):
- Changes take 10-14 days to appear
- 30-50% bone loss needed to see lysis
- Look for: periosteal reaction, lytic lesions, sequestrum, involucrum
MRI (gold standard):
- 90% sensitive, 80% specific
- Shows marrow oedema (T2 hyperintense)
- Differentiates abscess from cellulitis
- Gadolinium enhances inflamed tissue
Nuclear medicine:
- Bone scan sensitive but not specific
- Labelled WCC scan more specific for infection
Microbiological Diagnosis
Tissue culture is the gold standard:
- Multiple deep samples (not sinus tract)
- Send for aerobic, anaerobic, fungal, TB cultures
- Minimum 3 samples increases yield
Blood cultures:
- Positive in 50% of acute haematogenous cases
- Usually negative in chronic osteomyelitis
Antibiotic timing:
- Hold antibiotics until cultures obtained
- Exception: septic patient requires empiric therapy
Sinus Tract Swabs are Unreliable
Cultures from sinus tract openings have only 50% concordance with deep bone cultures. Do NOT base antibiotic choice on superficial swabs - they grow skin commensals and colonizers, not the true pathogen. Always obtain intraoperative bone and tissue cultures before starting definitive antibiotics.
Brodie's Abscess (Subacute Osteomyelitis)
Diabetic Foot Osteomyelitis
Management Algorithm
Treatment Algorithm for Chronic Osteomyelitis
Confirm osteomyelitis: Clinical (pain, draining sinus), imaging (MRI), inflammatory markers (CRP). Hold antibiotics pending cultures. Plan surgical intervention.
Radical debridement of all necrotic tissue. Remove all sequestra, open medullary canal, excise sinus tracts. Obtain minimum 3 deep tissue cultures. Send specimen for histology. Dead space management (antibiotic beads, muscle flap, bone graft).
Organism-specific IV antibiotics for 2-4 weeks. Australian eTG: flucloxacillin 2g IV 6-hourly for MSSA. Vancomycin for MRSA. Adjust based on culture sensitivities. Monitor CRP weekly - should fall by 50% at 2 weeks.
Switch to oral antibiotics when clinically improving and CRP falling. Total duration 6 weeks minimum. High bioavailability agents: fluoroquinolones, clindamycin, linezolid. Continue until CRP normalizes and patient asymptomatic.
Definitive reconstruction if needed. Bone transport for segmental defects. Free fibula for massive defects. Arthrodesis for joint involvement. Only proceed once infection controlled (normal CRP, no drainage).
Australian Antibiotic Guidelines (eTG)
First-Line Antibiotic Choices (eTG 2024)
| Organism | First-Line IV | Oral Step-Down | Duration |
|---|---|---|---|
| MSSA | Flucloxacillin 2g IV 6-hourly | Flucloxacillin 1g PO 6-hourly | 6 weeks total |
| MRSA | Vancomycin 25-30 mg/kg IV loading | Linezolid 600mg PO 12-hourly | 6 weeks total |
| Streptococcus | Benzylpenicillin 1.8g IV 4-hourly | Amoxicillin 1g PO 8-hourly | 6 weeks total |
| Gram-negative | Ceftriaxone 2g IV daily | Ciprofloxacin 750mg PO 12-hourly | 6 weeks total |
| Pseudomonas | Piperacillin-tazobactam 4.5g IV 6-hourly | Ciprofloxacin 750mg PO 12-hourly | 6-8 weeks |
Evidence Base
Acute Osteomyelitis Treatment Duration
- RCT comparing short-course (20 days) vs long-course (30 days) IV antibiotics
- No difference in recurrence rates at 1 year
- Shorter IV course equally effective when followed by oral therapy
- CRP normalization correlates with cure
Chronic Osteomyelitis and Biofilm
- Biofilm bacteria are 1000x more resistant to antibiotics than planktonic forms
- Glycocalyx matrix prevents antibiotic and immune cell penetration
- Rifampicin shows activity against biofilm Staphylococci
- Surgical debridement remains essential for chronic infection
Surgical Debridement for Chronic Osteomyelitis
- Systematic review of surgical techniques for chronic osteomyelitis
- Radical debridement with dead space management achieves 70-90% cure rates
- Muscle flaps provide better results than local wound care
- Staged approach allows infection control before reconstruction
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Chronic Tibial Osteomyelitis Classification
"A 45-year-old male presents 18 months after open tibial fracture ORIF. He has persistent drainage from the anterior shin. MRI shows intramedullary signal abnormality with cortical sequestrum but the tibia appears structurally intact. CRP 45. How would you classify and manage this?"
Scenario 2: Pediatric Acute Osteomyelitis Pathophysiology
"Explain why acute haematogenous osteomyelitis in children typically affects the metaphysis of long bones, and why it can lead to septic arthritis in some cases but not others."
MCQ Practice Points
Most Common Organism Question
Q: What is the most common causative organism in all age groups for osteomyelitis? A: Staphylococcus aureus - causes 80-90% of all osteomyelitis cases regardless of age. The exception is sickle cell disease where Salmonella is more common than S. aureus.
Biofilm Resistance Question
Q: Bacteria within biofilm are how many times more resistant to antibiotics than planktonic bacteria? A: 1000 times more resistant - this is why surgical debridement is mandatory for chronic osteomyelitis. Antibiotics cannot penetrate the glycocalyx matrix.
MRI Sensitivity Question
Q: What is the sensitivity of MRI for diagnosing osteomyelitis? A: 90% sensitive - MRI is the gold standard imaging modality, showing marrow oedema and soft tissue extension. Plain radiographs take 10-14 days to show changes.
Australian Antibiotic Guideline Question
Q: What is the eTG first-line antibiotic for MSSA osteomyelitis? A: Flucloxacillin 2g IV 6-hourly - narrow spectrum beta-lactamase resistant penicillin. For MRSA, use vancomycin with trough monitoring.
Australian Context
eTG Antibiotic Guidelines
Therapeutic Guidelines: Antibiotic (eTG version 17, 2024):
- MSSA: Flucloxacillin preferred over cefazolin
- MRSA: Vancomycin with trough 15-20 mg/L
- Duration: Minimum 6 weeks total therapy
- Oral step-down when clinically improving
- High bioavailability agents preferred (ciprofloxacin, clindamycin, linezolid)
ACSQHC Standards
Australian Commission on Safety and Quality in Health Care:
- Antimicrobial Stewardship Standard applies
- Culture before antibiotics where possible
- Document indication, dose, duration
- Review at 48-72 hours based on cultures
- Audit compliance with guidelines
Medicolegal Considerations
Key documentation requirements:
- Culture results before starting antibiotics (unless septic)
- Justification for antibiotic choice if deviating from eTG
- Informed consent for surgery discussing recurrence risk (10-30% chronic osteomyelitis)
- Multidisciplinary input (infectious diseases, microbiology, plastics for flaps)
- Clear treatment duration and monitoring plan
Common litigation: starting antibiotics before cultures obtained, inadequate debridement, sinus tract culture used instead of deep tissue.
OSTEOMYELITIS PATHOPHYSIOLOGY
High-Yield Exam Summary
Key Pathophysiology
- •Biofilm on sequestrum = 1000x antibiotic resistance
- •Metaphyseal sinusoidal flow = seeding site in children
- •Sequestrum = dead bone, Involucrum = new bone shell
- •Elevated intraosseous pressure causes vascular compromise
Cierny-Mader Classification
- •Type I = Medullary, Type II = Superficial
- •Type III = Localized (stable after debridement)
- •Type IV = Diffuse (unstable after debridement)
- •A = Normal host, B = Compromised, C = Treatment worse than disease
Microbiology
- •S. aureus = 80% all cases
- •Pseudomonas = puncture wound through shoe
- •Salmonella = sickle cell disease
- •Polymicrobial = diabetic foot, trauma
Diagnosis
- •MRI = 90% sensitive - gold standard
- •CRP > ESR for monitoring treatment
- •Deep tissue culture (NOT sinus tract swab)
- •Plain XR needs 10-14 days to show changes
Treatment
- •Surgery + antibiotics synergistic
- •Debride all necrotic tissue and sequestra
- •6 weeks total antibiotics (2-4 weeks IV, rest oral)
- •eTG: Flucloxacillin for MSSA, vancomycin for MRSA