FUNGAL SPINE INFECTIONS
Rare but Devastating | Immunocompromised Hosts | Prolonged Therapy Required
Common Fungal Pathogens in Spine
Critical Must-Knows
- Candida and Aspergillus account for 75% of fungal spine infections in immunocompromised patients
- Diagnosis requires tissue biopsy with fungal cultures (blood cultures often negative)
- MRI shows paravertebral abscess and epidural extension more commonly than bacterial infections
- Treatment requires prolonged antifungal therapy (6-12 months) PLUS surgical debridement if neurological compromise
- Mortality reaches 30-50% in disseminated aspergillosis despite treatment
Examiner's Pearls
- "Think fungal in immunocompromised patient with spine infection not responding to antibacterial therapy
- "Beta-D-glucan and galactomannan serum assays help diagnose invasive fungal infection
- "Endemic mycoses (Coccidioides, Histoplasma) occur in specific geographic regions - travel history critical
- "Aspergillus causes bony destruction with less disc involvement compared to bacterial infections
Critical Fungal Spine Infection Exam Points
High-Risk Populations
Immunocompromised hosts are primary targets. HIV/AIDS with CD4 less than 100, solid organ transplant recipients on immunosuppression, hematological malignancies undergoing chemotherapy, chronic corticosteroid use (greater than 20mg prednisone daily for over 3 weeks), diabetes mellitus with poor glycemic control.
Diagnostic Challenge
Blood cultures often negative (60-70% of cases). Requires tissue biopsy via CT-guided needle or open surgical biopsy. Send fresh tissue for fungal culture (NOT formalin) and fungal stains (GMS, PAS). Fungal cultures take 2-6 weeks to grow. Molecular testing (PCR) and serology (beta-D-glucan, galactomannan) aid rapid diagnosis.
MRI Characteristics
Paravertebral and epidural extension more common than bacterial. T2 hyperintense paraspinal masses often with rim enhancement. Subligamentous spread uncommon. Bony destruction may be more prominent than disc involvement especially in Aspergillus. Multiple non-contiguous levels suggest hematogenous dissemination.
Treatment Duration
Minimum 6-12 months antifungal therapy. Much longer than bacterial infections (6 weeks). Treat until clinical resolution, CRP normalization, and radiographic improvement. Surgical debridement if neurological deficit, spinal instability, or failure of medical therapy. Lifelong suppression may be needed in severe immunosuppression.
FUNGALRisk Factors for Fungal Spine Infection
Memory Hook:When spine infection is FUNGAL - look for these key risk factors in patient history!
CACAOCommon Fungal Pathogens
Memory Hook:Think CACAO when considering fungal spine infection - the sweet (but deadly) pathogens!
SPORETreatment Principles
Memory Hook:Treat fungal spine infections like SPORES - they take time to eradicate and require comprehensive approach!
Overview and Epidemiology
Fungal spine infections (fungal spondylodiscitis or vertebral osteomyelitis) are rare but serious infections accounting for only 1-2% of all spinal infections. However, incidence is rising due to increasing numbers of immunocompromised patients from HIV, solid organ transplantation, chemotherapy, and chronic immunosuppressive medications.
Why Fungal Spine Infections Matter
Fungal spine infections are easily missed because they mimic bacterial infections clinically but do not respond to antibacterial therapy. Delayed diagnosis leads to progressive neurological deficit, spinal instability, and disseminated disease with high mortality (30-50% in aspergillosis). High index of suspicion required in immunocompromised patients with spine infection. Tissue biopsy is gold standard for diagnosis.
Demographics and Risk Factors
Immunocompromised hosts predominate:
- HIV/AIDS with CD4 less than 100 cells/mcL
- Solid organ transplant recipients
- Hematological malignancies (leukemia, lymphoma)
- Chronic corticosteroid use (greater than 20mg/day for more than 3 weeks)
- Diabetes mellitus with HbA1c greater than 9%
- IV drug use (Candida from contaminated needles)
- Recent spine surgery or invasive procedures
Geographic Distribution
Endemic mycoses have specific geography:
- Coccidioides: Southwest USA (California, Arizona, New Mexico)
- Histoplasma: Mississippi and Ohio River valleys
- Blastomyces: Great Lakes region, Mississippi valley
- Cryptococcus: Worldwide but higher in AIDS patients
- Aspergillus and Candida: Worldwide, nosocomial
Pathophysiology and Microbiology
Routes of Infection
| Route | Common Organisms | Clinical Scenario | Spinal Involvement |
|---|---|---|---|
| Hematogenous spread | Candida, Aspergillus, endemic fungi | Disseminated infection from lungs, GI tract, or bloodstream | Vertebral body and disc via arterial seeding, often multifocal |
| Direct inoculation | Candida, Aspergillus | Postoperative infection from contaminated surgical field or implants | Localized to surgical site, may involve hardware |
| Contiguous spread | Actinomyces (cervical) | Extension from adjacent site (retropharyngeal, mediastinal) | Progressive involvement of adjacent vertebrae and soft tissues |
Specific Fungal Pathogens
Candida Spondylodiscitis
Most common fungal pathogen (50% of cases)
Species: C. albicans most common, but C. glabrata, C. tropicalis, C. parapsilosis increasingly recognized
Risk factors:
- Prolonged ICU stay with central lines
- Total parenteral nutrition (TPN)
- Recent broad-spectrum antibiotics
- Abdominal surgery
- IV drug use
Clinical features:
- Indolent onset over weeks to months
- Back pain with low-grade fever
- Often diagnosed late when neurological deficit develops
Treatment:
- Fluconazole 400-800mg daily PO for susceptible species (C. albicans, C. tropicalis)
- Echinocandin (micafungin 100mg IV daily) for resistant species or critically ill patients
- Duration: minimum 6 months, up to 12 months if extensive disease
Candida has good disc involvement with disc space narrowing on imaging.
Clinical Presentation
Clinical Features
Symptoms
Indolent onset over weeks to months:
- Back pain (90%) - insidious, progressively worsening
- Low-grade fever (40-60%) - may be absent
- Night sweats and weight loss (40%)
- Radicular pain if nerve root compression (30%)
- Neurological deficit (50-70%) - often presents late
- Constitutional symptoms less prominent than bacterial
Physical Examination
Focal findings:
- Spine tenderness at affected level
- Reduced range of motion
- Neurological exam: motor, sensory, reflex deficits
- Assess for epidural abscess: saddle anesthesia, bowel/bladder dysfunction
- Look for other sites: pulmonary (crackles), skin lesions, retinal lesions (Candida endophthalmitis)
Investigations
Diagnostic Approach
Diagnostic Workup for Suspected Fungal Spine Infection
Inflammatory markers: ESR and CRP elevated but less dramatically than bacterial (ESR 40-80mm/hr typical) Complete blood count: Leukocytosis may be absent, anemia of chronic disease common Blood cultures: Positive in only 30-40% of fungal infections (versus 50-60% bacterial) Fungal serology: Beta-D-glucan (Candida, Aspergillus), galactomannan (Aspergillus), Coccidioides serology if endemic exposure HIV testing: All patients with suspected fungal infection should be tested for HIV
MRI spine with contrast (GOLD STANDARD): Shows extent of vertebral involvement, disc involvement, paravertebral abscess, epidural extension, neural compression. T2 hyperintense paraspinal masses with rim enhancement characteristic. Aspergillus shows more bone destruction, less disc involvement. CT spine: Better defines bony destruction and cortical integrity. Useful for surgical planning. Chest/abdominal CT: Evaluate for pulmonary or disseminated fungal infection (aspergillosis, coccidioidomycosis).
CT-guided needle biopsy (initial approach): Send fresh tissue (NOT formalin) for fungal culture and bacterial culture. Also send for fungal stains (GMS, PAS) and AFB stains. Cultures may take 2-6 weeks to grow. Open surgical biopsy if needle biopsy non-diagnostic or neurological deficit requiring decompression: Obtain multiple tissue samples from vertebral body, disc, and abscess. Send fresh tissue for cultures and histopathology. Histopathology: Look for granulomas, fungal elements on GMS or PAS stains. Characteristic morphology helps identify organism (Aspergillus: septate hyphae with acute-angle branching).
PCR testing: Rapid identification of Aspergillus, Candida, endemic fungi from tissue or fluid samples MALDI-TOF mass spectrometry: Rapid species identification from culture isolates Antifungal susceptibility testing: Essential for Candida (resistance to fluconazole common in C. glabrata) and Aspergillus
Tissue Biopsy is Gold Standard
Blood cultures are negative in 60-70% of fungal spine infections. Empiric antibacterial therapy often started before fungal diagnosis considered. High index of suspicion required when spine infection fails to improve on appropriate antibiotics. Tissue biopsy (CT-guided or open surgical) is MANDATORY for definitive diagnosis. Do NOT send tissue in formalin - send FRESH for culture. Fungal cultures take 2-6 weeks, so maintain suspicion and consider empiric antifungal therapy while awaiting results.
Imaging Characteristics
MRI Findings: Bacterial versus Fungal Spine Infection
| Feature | Bacterial | Fungal (Candida) | Fungal (Aspergillus) |
|---|---|---|---|
| Disc involvement | Early and prominent | Moderate | Minimal or late |
| Vertebral body destruction | Moderate | Moderate | Severe and extensive |
| Paravertebral abscess | Common (50-70%) | Very common (70-90%) | Very common (80-90%) |
| Epidural extension | 30-50% | 50-70% | 60-80% |
| Subligamentous spread | Common (contiguous levels) | Less common | Rare |
| Multiple non-contiguous levels | Rare (unless bacteremia) | Common (hematogenous) | Common (hematogenous) |
Management
Treatment Algorithm
Antifungal Therapy by Organism
| Organism | First-Line Treatment | Alternative | Duration |
|---|---|---|---|
| Candida albicans | Fluconazole 400-800mg PO daily | Micafungin 100mg IV daily | 6-12 months |
| Candida glabrata (resistant) | Micafungin 100mg IV daily | Caspofungin 70mg loading, then 50mg daily | 6-12 months |
| Aspergillus | Voriconazole 200mg PO BID (after loading) | Liposomal amphotericin B 5mg/kg IV daily | 12 weeks to 12 months |
| Coccidioides | Fluconazole 400-800mg PO daily | Liposomal amphotericin B (severe cases) | 12-18 months, often lifelong |
| Histoplasma | Itraconazole 200mg PO BID | Liposomal amphotericin B (severe cases) | 12+ months |
Antifungal Therapy Principles
Fungal spine infections require PROLONGED therapy (minimum 6-12 months, often longer) compared to bacterial infections (6 weeks). Treat until clinical resolution, CRP normalization, and radiographic improvement. Monitor drug levels for voriconazole and itraconazole (significant inter-patient variability). Combination therapy (medical PLUS surgical) often needed for optimal outcomes. Lifelong suppressive therapy may be necessary in patients who remain severely immunosuppressed (AIDS with CD4 less than 100, transplant recipients).
Monitoring and Follow-up
- Clinical response: Monitor pain, fever, neurological status weekly initially
- Inflammatory markers: CRP and ESR monthly - should trend down over 3-6 months
- Drug levels: Voriconazole trough 1-5.5mcg/mL, itraconazole trough greater than 1mcg/mL
- Toxicity monitoring: LFTs monthly (azole hepatotoxicity), creatinine (amphotericin nephrotoxicity), visual changes (voriconazole)
- Imaging: MRI at 3 months and 6 months to assess response - expect slow radiographic improvement
Failure to improve clinically or radiographically at 3 months suggests need for surgical intervention or change in antifungal regimen.
Complications and Outcomes
| Complication | Incidence | Risk Factors | Management |
|---|---|---|---|
| Disseminated fungal infection | 20-40% in Aspergillus | Severe immunosuppression, delay in diagnosis | Systemic antifungals, manage end-organ dysfunction, high mortality 30-50% |
| Progressive neurological deficit | 30-50% if untreated | Epidural abscess, delayed diagnosis, medical therapy failure | Urgent surgical decompression, continue antifungals, outcomes variable |
| Spinal deformity (kyphosis) | 40-60% with vertebral collapse | Aspergillus (severe bone destruction), inadequate reconstruction | Surgical correction with anterior column support and posterior instrumentation |
| Treatment failure/relapse | 20-30% | Inadequate debridement, premature discontinuation of antifungals, persistent immunosuppression | Repeat debridement, change antifungal regimen, prolong therapy, address immune status |
| Antifungal toxicity | 30-40% | Prolonged therapy, liver disease, drug interactions | Monitor LFTs monthly, adjust doses, switch agents if severe hepatotoxicity |
Prognostic Factors
Good Prognosis Factors
- Candida infection (versus Aspergillus)
- Limited spinal involvement (1-2 levels)
- No neurological deficit at presentation
- Ability to reverse immunosuppression (reduce steroids, control HIV)
- Early diagnosis and treatment initiation
- Surgical debridement when indicated
Poor Prognosis Factors
- Aspergillus or mucormycosis infection
- Disseminated disease
- Severe baseline immunosuppression (CD4 less than 50)
- Delayed diagnosis (greater than 3 months from symptom onset)
- Extensive vertebral destruction (greater than 50% height loss)
- Complete neurological deficit (paraplegia)
Outcomes
Candida spondylodiscitis: Favorable outcomes with early diagnosis and treatment. Combination therapy (surgical debridement plus prolonged fluconazole) results in 70-80% cure rate. Neurological recovery occurs in 80-90% of patients undergoing early decompression.
Aspergillus spondylodiscitis: Guarded prognosis with 30-50% mortality if disseminated. Localized spinal aspergillosis has better outcomes (70-80% survival) with aggressive surgical debridement and voriconazole therapy.
Endemic mycoses: Chronic course requiring lifelong suppressive therapy in many cases. Coccidioidomycosis has 60-70% response rate to fluconazole but relapses common if therapy discontinued.
Evidence Base
Fungal Vertebral Osteomyelitis: Systematic Review
- Systematic review of 308 cases of fungal vertebral osteomyelitis from 1950-2014
- Candida (36%), Aspergillus (23%), Coccidioides (12%) most common organisms
- Neurological deficit at presentation in 52% of cases
- Combination surgical and medical therapy had better outcomes than medical alone (cure rate 78% vs 54%)
- Mean duration of antifungal therapy was 8.6 months (range 1-36 months)
Voriconazole for Invasive Aspergillosis
- Randomized trial of 277 patients with invasive aspergillosis: voriconazole vs amphotericin B
- Voriconazole superior to amphotericin B for survival (71% vs 58% at 12 weeks)
- Complete or partial response higher with voriconazole (53% vs 32%)
- Fewer nephrotoxicity and infusion-related events with voriconazole
Fluconazole for Candida Osteomyelitis
- IDSA guidelines recommend fluconazole 400mg (6mg/kg) daily for Candida osteomyelitis
- Duration: 6-12 months, longer if immunocompromised or slow response
- Echinocandin (micafungin, caspofungin) for azole-resistant species or critically ill
- Surgical debridement recommended for extensive disease or neurological compromise
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Immunocompromised Patient with Spine Infection (Standard)
"A 52-year-old renal transplant recipient on tacrolimus and prednisone presents with 6 weeks of progressive low back pain and low-grade fever. He was treated with 2 weeks of IV cefazolin for presumed bacterial spondylodiscitis without improvement. MRI shows L3-L4 spondylodiscitis with large paravertebral abscess and mild epidural extension. Blood cultures are negative. How would you approach this case?"
Scenario 2: Aspergillus Spondylodiscitis with Neurological Deficit (Challenging)
"A 45-year-old woman with acute myeloid leukemia post-chemotherapy presents with acute onset bilateral lower extremity weakness and urinary retention. She has had 4 weeks of back pain. MRI shows T10-T11 spondylodiscitis with severe vertebral body destruction and epidural abscess causing cord compression. CT-guided biopsy 2 weeks ago grew Aspergillus fumigatus. She has been on voriconazole 200mg BID for 10 days. Exam shows 2/5 bilateral lower extremity strength and T10 sensory level. How do you manage this patient?"
Scenario 3: Endemic Mycosis - Coccidioidomycosis (Critical)
"A 38-year-old previously healthy man who recently moved from Arizona to Australia presents with 6 months of progressive back pain, night sweats, and 10kg weight loss. MRI shows multifocal spondylodiscitis at L1-L2 and L4-L5 with extensive paravertebral abscesses bilaterally. He has mild lower extremity weakness (4/5). Coccidioides serology is positive with high titers. How would you counsel and manage this patient?"
MCQ Practice Points
Most Common Pathogen Question
Q: What is the most common fungal pathogen causing spondylodiscitis? A: Candida species (50% of cases) - Most common fungal pathogen, followed by Aspergillus (25%). Candida spondylodiscitis typically occurs in healthcare-associated settings (ICU, central lines, TPN) or in IV drug users. Treatment is fluconazole 400-800mg daily for 6-12 months.
Diagnostic Test Question
Q: What is the gold standard for diagnosing fungal spine infection? A: Tissue biopsy with fungal culture - Blood cultures are negative in 60-70% of fungal spine infections. Tissue biopsy (CT-guided needle or open surgical) is mandatory. Send FRESH tissue (NOT formalin) for fungal culture and fungal stains (GMS, PAS). Cultures take 2-6 weeks to grow. Serology (beta-D-glucan, galactomannan) and PCR can aid rapid diagnosis.
First-Line Therapy Question
Q: What is the first-line antifungal for invasive aspergillosis including spinal involvement? A: Voriconazole - NEJM 2002 trial showed voriconazole superior to amphotericin B for invasive aspergillosis (71% vs 58% survival at 12 weeks). Dose: 200mg PO BID after loading dose. Monitor drug levels (target trough 1-5.5mcg/mL). Alternative: liposomal amphotericin B 5mg/kg IV daily. Duration: minimum 12 weeks, often 6-12 months for spinal disease.
Imaging Findings Question
Q: What MRI finding is more characteristic of fungal versus bacterial spine infection? A: Extensive paravertebral and epidural extension with relative disc sparing (especially Aspergillus) - Fungal infections more commonly have large paraspinal abscesses (70-90% vs 50-70% bacterial) and epidural extension (50-80% vs 30-50% bacterial). Aspergillus preferentially destroys bone with less disc involvement compared to bacterial infections. Multiple non-contiguous levels suggest hematogenous fungal dissemination.
Endemic Mycosis Question
Q: A patient with disseminated coccidioidomycosis and spinal involvement asks how long antifungal therapy will be needed. What do you tell them? A: Lifelong suppressive therapy is often required for disseminated coccidioidomycosis - Unlike localized pulmonary disease (treat 3-6 months), disseminated coccidioidomycosis with spinal involvement requires prolonged therapy (minimum 12-18 months, often lifelong) to prevent relapse. Relapse rates 20-30% if therapy discontinued in disseminated disease. Treatment is fluconazole 400mg daily or higher doses.
Surgical Indication Question
Q: What are the absolute indications for surgical intervention in fungal spine infection? A: Progressive neurological deficit, spinal instability, epidural abscess with cord compression, medical treatment failure - Combination therapy (surgery PLUS antifungals) has better outcomes than medical therapy alone (cure rate 78% vs 54%). Surgery provides tissue diagnosis, decompresses neural elements, debrides infected tissue, and allows definitive pathogen identification. Medical failure defined as progression despite 4-6 weeks of appropriate antifungal therapy.
FUNGAL SPINE INFECTIONS
High-Yield Exam Summary
Key Pathogens and Epidemiology
- •Candida (50%) - healthcare-associated, IV drug use, immunocompromised
- •Aspergillus (25%) - hematological malignancies, transplant, high mortality 30-50% if disseminated
- •Coccidioides - endemic Southwest USA, disseminated disease requires lifelong therapy
- •Histoplasma/Blastomyces - endemic mycoses, Mississippi/Ohio valleys and Great Lakes region
- •Only 1-2% of all spine infections but rising incidence due to more immunocompromised patients
Clinical Recognition
- •Think fungal if spine infection fails to respond to appropriate antibacterial therapy
- •Indolent onset over weeks to months with low-grade fever (or absent)
- •Neurological deficit in 50-70% (often late presentation)
- •Risk factors: HIV CD4 less than 100, transplant, chemotherapy, chronic steroids greater than 20mg daily, diabetes
- •Blood cultures negative in 60-70% - tissue biopsy is MANDATORY
Diagnostic Approach
- •MRI: extensive paravertebral/epidural extension more than bacterial, disc sparing in Aspergillus
- •Tissue biopsy (CT-guided or surgical) is gold standard - send FRESH (NOT formalin) for culture
- •Fungal stains: GMS (Grocott methenamine silver), PAS (periodic acid-Schiff)
- •Serology: beta-D-glucan (Candida/Aspergillus), galactomannan (Aspergillus), Coccidioides titers
- •Fungal cultures take 2-6 weeks to grow - consider empiric therapy in high-risk patients
Treatment by Organism
- •Candida albicans: fluconazole 400-800mg daily PO × 6-12 months
- •Candida glabrata (resistant): micafungin 100mg IV daily × 6-12 months
- •Aspergillus: voriconazole 200mg BID PO (monitor levels) × 12 weeks to 12 months
- •Coccidioides disseminated: fluconazole 400-800mg daily, often lifelong suppression
- •Surgery if neurological deficit, instability, medical failure, or extensive destruction
Surgical Indications and Approach
- •Absolute: progressive neuro deficit, spinal instability, epidural abscess with cord compression, medical failure
- •Combination therapy (surgery + antifungals) superior to medical alone (cure 78% vs 54%)
- •Posterior decompression for epidural abscess, laminectomy, instrumentation if instability
- •Anterior corpectomy for vertebral body destruction, reconstruct with cage (avoid autograft)
- •Combined anterior-posterior for severe destruction, maximum debridement and stability
Outcomes and Prognosis
- •Candida: 70-80% cure rate with combination therapy, good neurological recovery if early surgery
- •Aspergillus disseminated: 30-50% mortality despite treatment, localized spinal 70-80% survival
- •Coccidioides disseminated: requires lifelong therapy, relapse 20-30% if discontinued
- •Treatment failure/relapse 20-30% overall - inadequate debridement, early discontinuation, persistent immunosuppression
- •Monitor CRP/ESR monthly (should trend down), MRI at 3 and 6 months, drug levels for voriconazole/itraconazole