Skull Base Osteomyelitis (SBO)

Definition and Historical Background

Epidemiology

• Incidence is increasing - from 67 cases (1999-2000) to 421 cases (2012-2013) in UK Hospital Episode Statistics
• Predominantly affects elderly (>60 years) and diabetics (65-100% of cases in various series)
• Male:female ratio 2:1
• Immunosuppressed states are increasingly recognized: HIV/AIDS (often fungal, younger patients, CD4 <50), steroid use, chemotherapy, haematological malignancies (leukaemia, lymphoma), renal transplantation
• HIV patients: younger, higher risk of fungal infection
• Pediatric SBO: rare; associated with IgA deficiency, monocytic leukaemia, neutropenia - Scott-Brown's, Vol. 2

Pathophysiology

1. Impaired polymorphonuclear leukocyte function (poor phagocytosis of Pseudomonas)
2. Microangiopathy and endarteritis - small vessel obliteration reduces local immune response
3. Elevated EAC cerumen pH in diabetics - favours bacterial colonisation
4. Breakdown of the cutaneous barrier of the EAC - eczema, seborrhoea, self-induced trauma from pruritus, ear canal irrigation

• CN VII (facial nerve) - most common; close relation to EAC at the stylomastoid foramen
• CN IX, X, XI - jugular foramen involvement
• CN XII (hypoglossal) - further medial spread
• CN VI, V - petrous apex involvement
• CN II - optic nerve, late extension

Bacteriology

Clinical Features

Symptoms

• Severe, deep-seated, nocturnal otalgia - disproportionate to examination findings; resistant to analgesics (prevalence 75-100%). This is the most common presenting symptom.
• Unilateral purulent otorrhoea - second most common
• Conductive hearing loss - from EAC oedema/granulation
• History of ear canal trauma (often after wax irrigation) is common

Signs

• Granulation tissue at the bony-cartilaginous junction (isthmus of EAC) - the cardinal hallmark sign; should never be underestimated
• Oedematous, exquisitely tender ear canal
• Exposed bone may be visible at the floor of the canal
• Tympanic membrane often intact initially; may be obscured by polyp or granuloma
• HIV patients often lack granulation tissue - making diagnosis harder

Cranial Nerve Involvement (in order of progression)

1. CN VII (facial nerve palsy) - up to 25% of patients; implies infection encasing the extratemporal portion or involving the stylomastoid foramen
2. CN IX, X, XI - jugular foramen involvement (glossopharyngeal, vagus, accessory)
3. CN XII - hypoglossal palsy, vocal cord paralysis
4. CN VI, V - petrous apex spread
5. Multiple cranial neuropathies = worse prognosis

Rare/Late Features

• Septic thrombophlebitis of sigmoid sinus - "picket fence" pattern of fevers
• Meningitis, cerebral abscess - late, poor prognosis
• Parotitis, trismus - masseter myositis and TMJ involvement
• Children: facial nerve palsies occur earlier (more medial fissures of Santorini, undeveloped mastoid)

Diagnosis

Laboratory

• ESR - elevated, non-specific; useful for monitoring treatment response and recurrence
• CRP - elevated; use to monitor treatment response
• WBC and fever may be absent (do not exclude diagnosis)
• Blood glucose - check and optimise

Biopsy

• Mandatory - granulation tissue must be biopsied to rule out malignancy, histiocytosis, tuberculosis, and for culture
• Silver staining on histology identifies fungal pathogens
• Histology shows inflammation without neoplasia

Microbiology

• EAC debris: culture and stain for bacteria, fungi, acid-fast bacilli
• If tympanic membrane intact and topical antibiotics have failed: tympanotomy/tympanocentesis for culture

Imaging

CT Scan

• Shows bony erosion and reduced density at skull base
• Only detects bony demineralisation >30% - limited early sensitivity; demineralisation may take months to appear
• A negative CT does not exclude SBO
• Contrast-CT: evaluates extratemporal soft tissue extent, abscesses, mastoid/TMJ involvement, petrous apex and carotid canal involvement
• Cannot reliably assess treatment response or distinguish neoplasia from inflammation
• Contrast not necessary unless abscess is suspected

MRI

• Superior for soft tissue and dural involvement; detects bone marrow oedema
• Better than CT for evaluating lateral sinus blood flow and intracranial extension
• Cannot reliably assess treatment response - may remain abnormal months after successful treatment
• Combine with MR angiography to evaluate dural sinus patency

Nuclear Medicine (key to monitoring)

Treatment

1. Aural Toilet

• Regular microsuction/debridement of the EAC - controls granulations and pain
• Controversy exists over concurrent topical antimicrobials (may hinder culture results)

2. Glycaemic Control

• Aggressive optimisation of blood glucose is as important as antibiotics in diabetic patients
• Poor glycaemic control makes SBO harder to treat and maintain in remission

3. Systemic Antibiotics (Mainstay of Treatment)

• Duration: Minimum 6-8 weeks; may extend to months in advanced cases
• Ideally continue until Gallium-67 scan is negative
• First line: Oral ciprofloxacin 750 mg twice daily (monotherapy; excellent antipseudomonal activity, good bone penetration, high oral bioavailability)
• Some experts advocate initial parenteral therapy, switching to oral when ESR/CRP begin to fall - no conclusive evidence either way
• Rifampicin 600 mg twice daily has been suggested as an addition - no direct evidence of added benefit

For Fluoroquinolone-Resistant Pseudomonas:

• Antipseudomonal cephalosporins: ceftazidime, cefepime
• Antipseudomonal penicillins: ticarcillin-clavulanate, piperacillin-tazobactam
• Aminoglycosides (in combination)
• Double coverage against Pseudomonas is started empirically after cultures

For Fungal SBO:

• Amphotericin B - antifungal of choice
• Can transition to oral itraconazole after successful amphotericin course

4. Hyperbaric Oxygen (HBO)

• Proposed mechanism: increases tissue pO2, relieves hypoxia, enhances oxidative killing of microbes
• A Cochrane review found no evidence from RCTs to support its use; remains adjunctive/investigational

5. Surgery

• Role is now very limited compared to the era when radical debridement was routine
• Indications:
  • Obtaining specimens for culture and histology
  • Local debridement of granulation tissue
  • Drainage of associated abscesses
  • Removal of dead sequestra
• Facial nerve decompression is NOT indicated - infection involves the extratemporal portion of the nerve, not the intratemporal canal, so decompression fails to address the actual site of involvement

Prognosis / Poor Prognostic Factors

• Cranial neuropathies (especially multiple)
• EAC granulations (paradoxically, their presence correlates with severity)
• Bilateral symptoms
• Positive Aspergillus cultures
• Meningitis, sigmoid sinus thrombosis, cerebral abscess - late complications with poor prognosis

Imaging Gallery

CT/MRI of persistent SBO: axial CT showing focal sclerosis (green arrow), coronal T1 post-contrast MRI with dural thickening and pachymeningeal enhancement along bilateral petrous pyramids (orange arrows), and persistent central SBO extending across the midline (red arrow).

Atypical bacterial SBO: CT showing expansion of left pterygopalatine fossa and mixed erosive/hyperostotic skull base changes; MRI with clivus marrow replacement (T1) and restricted diffusion (DWI) in pterygoid base and infratemporal fossa.

Right central SBO: non-contrast CT (bone window) showing cortical erosion and bony destruction (asterisk); T1 Dixon MRI showing extensive infiltrating soft tissue mass involving right skull base, upper neck, occipital bone, and jugular bulb region (white arrows).

Recent Literature (2023-2025)

Grades / Staging of Skull Base Osteomyelitis

1. Chandler's Staging System (1977) - Classic / Most Widely Used

• Progression from I → IV represents increasing severity and worsening prognosis
• The Tc-99 bone scan is the pivotal investigation that separates Stage I from Stage II
• Facial nerve (CN VII) is the most commonly affected nerve in Stage III (up to 25-60% of cases)
• Stage IV carries the worst prognosis; intracranial extension historically associated with very high mortality
• Stage IIIb (multiple cranial nerve palsies) and Stage IV are considered advanced disease

2. Chandler's Original Grading (1968) - Historical

3. Lee et al. Prognosis-Based Classification (2008)

• Presence/absence of cranial nerve involvement
• Bacterial vs. fungal aetiology (fungal = worse prognosis)
• Extent of bony involvement on imaging
• Response to initial therapy

4. Takahashi et al. Radiological Staging System (2022) - HRCT/MRI Based

5. Özer et al. Clinicoradiological Grading System (2021)

• Regression rate (disease control) decreased from CG1 → CG3 (p = 0.029)
• Duration of hospitalization increased with higher CG (p = 0.047)
• 5-year overall survival: 45.8% overall; CG significantly correlated with overall survival (p = 0.017)
• Surgery had no significant effect on regression at discharge (p = 0.41)
• 1-year survival 82.2%, 2-year 70.8%, 5-year 45.8%

Summary Comparison

Important Prognostic Notes

• CN VII palsy alone - earlier literature suggested poor prognosis; more recent data (Corey, Soudry, Mani) suggests facial nerve palsy alone does not necessarily worsen prognosis
• Multiple cranial nerve palsies (IIIb) - consistently associated with worse outcomes across all systems
• Positive Aspergillus cultures - worse prognosis than Pseudomonas in all grading contexts
• Intracranial extension (Stage IV / Stage 3-4 Takahashi) - highest mortality; associated with sigmoid sinus thrombosis, meningitis, brain abscess

Melioidosis

Definition and Causative Organism

Epidemiology

• Southeast Asia (northeastern Thailand is hyperendemic), Philippines, Indonesia, Malaysia, Singapore
• Northern Australia (Darwin region is hyperendemic - the 30-year Darwin Prospective Melioidosis Study has been landmark)
• South Asia (India), southern China, Hong Kong, Taiwan
• Increasingly recognized in: Africa, Middle East, Central and South America
• Gulf Coast of the USA (B. pseudomallei found in environment; local cases reported in Texas)
• Contaminated imported products (e.g., aromatherapy spray from India) have caused outbreaks in non-endemic areas

• Diabetes mellitus - the single most common risk factor (present in majority of cases)
• Alcohol use disorder
• Chronic kidney disease / renal failure
• Chronic lung disease (COPD, bronchiectasis, cystic fibrosis in endemic areas)
• Heart disease, smoking
• HIV/AIDS and other immunosuppressive states
• Military personnel and travelers to endemic areas

Microbiology / Organism Characteristics

Routes of Infection

1. Percutaneous inoculation - direct contact of abraded/lacerated skin with contaminated soil or water (most common)
2. Inhalation of aerosolized bacteria (especially during heavy rain/typhoons; probable during storms)
3. Ingestion of contaminated water or food
4. Sexual intercourse (rare, documented)
5. Laboratory acquisition - biosafety concern

Clinical Spectrum

1. Asymptomatic / Subclinical Infection

• Demonstrated by seroprevalence studies in endemic areas
• Most common in healthy individuals

2. Acute Localized Infection

• Skin ulcers, cellulitis, subcutaneous abscesses
• Genitourinary infection (prostatic abscesses - particularly common in men in endemic areas; important clue)
• Lymphadenitis
• Septic arthritis, osteomyelitis
• Parotid abscesses (characteristic in children in Thailand)

3. Pulmonary Melioidosis (Most Common Form - ~50% of cases)

• Fever, productive cough, dyspnea
• Hemoptysis and pleuritic chest pain may be prominent
• Can present as rapid respiratory failure with signs of sepsis
• CXR: consolidation, often upper lobe involvement (~50%), multilobe in ~1/3
• Can progress to bacteraemia (63% of primary pneumonia cases) and septic shock (33%)

• Symptoms >2 months
• Fever, weight loss, chronic productive cough ± hemoptysis
• CXR: upper lobe cavitary disease mimicking tuberculosis
• Diffuse miliary nodules that can expand and cavitate

4. Septicaemic Melioidosis

• Most severe form
• Fever, prostration, signs of sepsis/septic shock
• Metastatic abscesses form in multiple organs: liver, spleen, kidneys, lungs, brain
• "Miliary" pattern of abscesses on imaging
• Over half of septicaemic patients have positive blood cultures
• Mortality 20-50% overall; up to 50-90% in untreated septicaemia (reduced to ~20% with aggressive ICU care)

5. Neurological Melioidosis

• Encephalomyelitis - described in the neurology literature (Adams and Victor)
• Brainstem encephalitis (particularly in northern Australia)
• Flaccid paralysis, fever, cranial nerve involvement
• Rare but severe manifestation

6. Chronic / Disseminated Melioidosis

• Characterized by abscesses and granulomas at multiple sites
• Can mimic tuberculosis, disseminated fungal infections, sarcoidosis
• Cutaneous manifestations: cellulitis, subcutaneous abscesses, granulomatous lesions, ecthyma gangrenosum, purpura, pustules, Sweet syndrome, urticaria, necrotizing fasciitis

Diagnosis

Gold Standard: Culture

• Culture of B. pseudomallei from any clinical specimen confirms diagnosis
• Specimens: blood, sputum, urine, pus/abscess aspirate, wound swab
• >50% of patients have positive blood cultures in septicaemia
• Grows readily on routine media; Ashdown's selective medium used for non-sterile sites
• Sensitivity of culture: as low as 60% overall

Microbiology Clues

• Gram stain: Gram-negative bacillus, bipolar ("safety-pin") staining
• Wrinkled, cream-coloured colonies; metallic odour

Molecular / PCR

• Multiplex PCR-based assays: more sensitive and species-specific than culture - increasingly used
• Useful when antibiotics already started

Serology

• Complement-fixing and agglutinating antibodies appear within 4-6 weeks of infection
• IHA (indirect haemagglutination assay) - used widely in endemic areas
• Not adequate alone in endemic regions (high background seropositivity); useful in non-endemic areas
• A 4-fold rise in titre is significant

Imaging

• CT chest: consolidation, upper lobe cavitation, miliary nodules
• CT abdomen/pelvis: hepatic, splenic, renal, or prostatic abscesses
• CT/MRI brain: if neurological involvement suspected

Key Points for Diagnosis

• Requires high index of suspicion - mimics many other conditions (TB, pneumonia, sepsis)
• Ask about travel to or residence in endemic areas
• Culture laboratories must be alerted (biosafety risk - BSL-3 pathogen)

Treatment

Phase 1: Intensive Phase (IV Antibiotics)

• Clinical deterioration on ceftazidime
• Persistent bacteraemia
• CNS involvement develops
• ICU admission required

Phase 2: Eradication Phase (Oral Antibiotics)

• Most presentations: 3 months
• Deep-seated/disseminated disease: may extend to 6-12 months
• Goal: prevent relapse (relapse rate ~10% without adequate eradication)

Drugs B. pseudomallei is intrinsically resistant to:

• First/second-generation penicillins (ampicillin, amoxicillin alone)
• First/second-generation cephalosporins
• Fluoroquinolones (ciprofloxacin, levofloxacin) - NOT effective empirically
• Macrolides
• Aminoglycosides
• Polymyxins
• Chloramphenicol (active but toxicity limits use in developed countries)

Complications and Prognosis

• Overall: 10-40% depending on presentation and setting
• Septicaemic form: 20-50% (up to 90% untreated)
• Indonesia (2024): mortality rate ~41%
• With aggressive ICU management: reduced to ~20%
• CNS involvement: poorest prognosis

• Septicaemic presentation
• CNS involvement
• Deep-seated abscesses
• Delayed diagnosis
• Immunosuppression / poorly controlled diabetes
• Absence of treatment in intensive phase with appropriate antibiotics

Special Considerations

Latency and Reactivation

• B. pseudomallei can remain latent in the body for decades
• US Vietnam War veterans developed melioidosis years after return ("Vietnamese time bomb")
• Reactivation can be triggered by immunosuppression, illness, or trauma

Bioterrorism

• B. pseudomallei (and B. mallei causing glanders) are listed as potential bioterrorism agents
• Biosafety Level 3 (BSL-3) pathogen - laboratory workers need protection
• Vaccine candidates in Phase 1 clinical trials (no licensed vaccine yet as of 2025-2026)

Paediatric Melioidosis

• Parotid gland abscesses are a characteristic presentation in children in Thailand
• Generally better prognosis than adults

The Darwin 30-Year Prospective Study

• The landmark natural history study (Currie et al., Lancet Infect Dis 2021) - 30 years of prospective data from Darwin, Australia, providing the most robust treatment and outcome data available

Recent Evidence (2022-2026)