Actinomycosis¶

Chapter 180 | Harrison's 22e · Part 5 – Infectious Diseases: Bacterial · Chapter 180

Key Clinical Points¶

Chronic, indolent infection caused by Actinomyces (anaerobic/microaerophilic), characterized by sulfur granules and contiguous tissue spread.
Most common agent is A. israelii (50-70%); infections are often polymicrobial with oral flora bacteria.
Commonly misdiagnosed as malignancy due to mass-like lesions, fibrotic 'wooden' texture, and lack of lymphadenopathy.
Key risk factors include IUD use (>1 year), bisphosphonate therapy (especially denosumab), and immunocompromise (HIV, transplant, CGD).
Pathognomonic finding: Sulfur granules (dense colonies of bacteria) with a Splendore-Hoeppli phenomenon (eosinophilic proteinaceous coating).
Clinical presentation varies by site: oral-cervicofacial (most common), thoracic/pulmonary, and abdominal/pelvic.
Thoracic cases may involve empyema, pleural effusion, and chest wall masses; often follows aspiration of foreign bodies.
Pelvic actinomycosis is frequently associated with IUDs, causing paraendometrial fibrosis and suppuration.
Treatment requires prolonged antibiotic therapy (typically ≥6 months) and surgical debridement for abscesses or sinus tracts.
Diagnosis confirmed via microscopy (sulfur granules) or culture (requires anaerobic conditions).

1. DEFINITION & OVERVIEW¶

Definition (Harrison's 22e): Actinomycosis is a chronic, indolent infection caused by anaerobic or microaerophilic bacteria of the genus Actinomyces, characterized by formation of sulfur granules and contiguous spread through tissues.

• Clinical Characteristics: ◦ Often mistaken for malignancy due to mass-like lesions and fibrotic 'wooden' texture ◦ Three classic presentations: chronic mass-like lesion, sinus tract formation, and refractory infection after short antibiotic course

1.1 Etiology & Pathogenesis¶

• Primary Pathogens: ◦ A. israelii (50-70% of cases) ◦ A. naeslundii, A. viscosus, Schaalia spp., Winkia neuii

• Polymicrobial Nature: ◦ Frequently involves oral flora: Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Fusobacterium spp., Bacteroides spp.

• Pathogenesis: ◦ Mucosal barrier disruption (e.g., dental trauma, IUDs, foreign bodies) → infection ◦ Contiguous spread through tissues ignoring anatomical planes ◦ Formation of central necrosis with sulfur granules (virtually diagnostic) ◦ Development of fibrotic walls described as 'wooden' ◦ Sinus tract formation to skin, adjacent organs, or bone

2. CLINICAL MANIFESTATIONS¶

• Clinical Syndromes: 1. Oral-cervicofacial disease (most common) 2. Thoracic/pulmonary disease 3. Abdominal/pelvic disease

• Oral-Cervicofacial Presentation: ◦ Soft tissue swelling/abscess in jaw angle ◦ Often mistaken for neoplasm ◦ Associated with dental procedures or radiation therapy ◦ Risk of MRONJ with bisphosphonates/denosumab

• Thoracic Disease: ◦ Indolent progression from aspirated foreign bodies (bones/teeth) ◦ Chest wall masses, empyema, pleural effusion ◦ May mimic lung cancer or tuberculosis

• Abdominal/Pelvic Disease: ◦ Chronic pelvic pain with IUD use (>1 year duration) ◦ Fibrotic masses with central necrosis ◦ Paraendometrial fibrosis and suppuration

2.1 Diagnostic Challenges¶

• Misdiagnosis: 70% of cases initially misdiagnosed as malignancy • Radiographic Features: ◦ Contiguous spread without lymphadenopathy ◦ Fibrotic masses with central necrosis ◦ Sinus tracts to skin/adjacent organs ◦ Presence of sulfur granules on microscopy or culture

3. DIAGNOSTIC APPROACH¶

• Imaging: ◦ CT/MRI: Identify fibrotic masses with central necrosis and contiguous spread ◦ Chest X-ray: Evaluate for thoracic mass with pleural effusion/empyema ◦ Pelvic ultrasound: Assess paraendometrial fibrosis with suppuration

• Microscopy: ◦ Sulfur granules (Actinomyces spp.) surrounded by neutrophils ◦ Splendore-Hoeppli phenomenon (eosinophilic proteinaceous coating)

• Culture & Microbiology: ◦ Gram stain: Look for beaded filamentous gram-positive rods ◦ Culture: Requires anaerobic conditions; may take weeks to grow

3.1 Diagnostic Algorithm (Flowchart)¶

Clinical Suspicion: Identify patients with chronic mass-like lesions, sinus tracts, or infections following IUD/bisphosphonate use.
Imaging Evaluation: ◦ Perform CT/MRI to look for 'woody' masses and contiguous spread. ◦ Perform CXR for thoracic involvement (empyema/pleural effusion). ◦ Perform Pelvic Ultrasound for paraendometrial fibrosis.
Microbiological Confirmation: ◦ Obtain tissue biopsy for microscopy (look for sulfur granules). ◦ Perform Gram stain (identify beaded filamentous rods). ◦ Culture under anaerobic conditions (expect growth over several weeks).
Treatment Determination: ◦ Assess severity to determine duration: ◦ Mild → 3-6 months ◦ Moderate → 6-12 months ◦ Severe/Relapsing → ≥12 months

4. MANAGEMENT & TREATMENT¶

• First-line Therapy: ◦ Penicillin G (24 million units/day IV) for ≥6 months

• Alternative Regimens: ◦ Amoxicillin: 1.5-2 g PO q8h for 6-12 months ◦ Clindamycin: 300 mg PO q6h for 6-12 months

• Surgical Intervention: ◦ Required for abscesses or sinus tracts

• Specialized Management: ◦ Bisphosphonate-associated cases: Discontinue denosumab if possible ◦ IUD-related: Remove device and treat for minimum 6 months post-removal

• Monitoring: ◦ Monthly follow-up for first 6 months ◦ Imaging to assess response to therapy

4.1 Evidence-Based Antibiotic Options (Table 1)¶

• Extensive Successful Clinical Experience: ◦ Penicillin: 3–4 million units IV q4h ◦ Amoxicillin: 500 mg PO q6h ◦ Erythromycin: 500–1000 mg IV q6h or 500 mg PO q6h ◦ Tetracycline: 500 mg PO q6h ◦ Doxycycline: 100 mg IV or PO q12h ◦ Minocycline: 100 mg IV or PO q12h ◦ Clindamycin: 900 mg IV q8h or 300–450 mg PO q6h

• Predicted In Vitro Efficacy: ◦ Vancomycin, Dalbavancin, Linezolid, Rifampin, Ertapenem, Meropenem, Tigecycline, Eravacycline, Azithromycin

4.2 Treatment Duration Guidelines¶

• Mild disease: 3-6 months of antibiotics ◦ Moderate disease: 6-12 months ◦ Severe/relapsing disease: ≥12 months with possible surgical intervention ◦ Bisphosphonate-associated cases: Minimum 6 months post-removal of IUD

Reference Tables¶

TABLE 180-1 Appropriate and Inappropriate Antibiotic Therapy for Actinomycosis a CATEGORY Extensive successful clinical…¶

Harrison's 22e, p.1366

CATEGORY	AGENT
Extensive successful clinical experienceb	Penicillin: 3–4 million units IV q4hc,d Amoxicillin: 500 mg PO q6h Erythromycin: 500–1000 mg IV q6h or 500 mg PO q6hc Tetracycline: 500 mg PO q6h Doxycycline: 100 mg IV or PO q12h Minocycline: 100 mg IV or PO q12h Clindamycin: 900 mg IV q8h or 300–450 mg PO q6hc
Agents predicted to be efficacious on the basis of in vitro activity	Vancomycin Dalbavancin Linezolid Rifampin Ertapenemd Meropenem Tigecyclined Eravacycline Azithromycind