Nocardiosis¶
Chapter 179 | Harrison's 22e · Part 5 – Infectious Diseases: Bacterial · Chapter 179
Key Clinical Points¶
- Nocardiae are Gram-positive, weakly acid-fast, catalase-positive bacteria containing mycolic acids in their cell walls.
- Pulmonary nocardiosis is common in immunocompromised patients and typically presents as nodular or cavitary lesions.
- Systemic disease involves the CNS in approximately 67% of cases, often presenting as multiloculated ring-enhancing brain abscesses.
- Cutaneous mycetoma (specifically N. brasiliensis) is characterized by 'grains' (granulomas), draining sinuses, and bone involvement.
- Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary first-line treatment for most Nocardia species.
- Host defense relies on neutrophils and macrophages; conditions like CGD or GM-CSF autoantibodies increase susceptibility.
- Risk factors include corticosteroid use, HSCT, HIV, CGD, and pulmonary alveolar proteinosis (PAP).
- Diagnosis requires culture (blood, sputum, tissue) or molecular testing (NAAT), supported by imaging (CT/MRI).
1. DEFINITION & OVERVIEW¶
• Definition: Nocardiosis is an opportunistic infection caused by aerobic, filamentous bacteria of the genus Nocardia. • Pathogen Characteristics: ◦ Ubiquitous in soil and water ◦ Over 50 species capable of causing human disease ◦ Common pathogens: N. farcinica, N. cyriacigeorgica, N. nova, and N. abscessus complex • Transmission Routes: ◦ Pulmonary (inhalation of fragmented mycelia) ◦ Cutaneous (direct inoculation) ◦ Systemic (hematogenous spread)
2. MICROBIOLOGY & PATHOGENESIS¶
• Microbiology: ◦ Gram-positive, weakly acid-fast, catalase-positive rods ◦ Contain mycolic acids in cell walls ◦ Growth: Chalky, wrinkled colonies on agar; optimal at 37°C • Pathogenesis & Host Defense: ◦ Inhalation of fragmented mycelia leads to pulmonary disease ◦ Neutrophils and macrophages are critical for host defense ◦ Survival mechanism: Nocardiae survive within phagocytes by neutralizing oxidants and preventing lysosome fusion • Associated Conditions: ◦ Autoantibodies to GM-CSF associated with pulmonary alveolar proteinosis (PAP) and increased nocardiosis risk
3. EPIDEMIOLOGY & RISK FACTORS¶
• Incidence: ~0.375 cases/100,000/year globally • High-Risk Groups: ◦ Transplant recipients (especially lung and solid organ) ◦ Immunosuppressed patients • Specific Risk Factors: ◦ Corticosteroid use ◦ Hematopoietic stem cell transplantation (HSCT) ◦ HIV infection ◦ Chronic granulomatous disease (CGD) ◦ Pulmonary alveolar proteinosis (PAP) • Demographic/Geographic Trends: ◦ Cutaneous infections: follow traumatic exposure to soil/vegetation ◦ Pulmonary disease: more common in males ◦ Mycetoma: predominantly in tropical regions
4. CLINICAL MANIFESTATIONS¶
• Pulmonary: ◦ Symptoms: cough, fever, pleuritic chest pain ◦ Imaging (Figure 2, Figure 7): nodules, cavitation, and pleural effusion • CNS: ◦ Involvement in ~67% of systemic cases ◦ Presentation: brain abscesses with multilobulated ring-enhancing lesions on MRI (Figure 4) • Cutaneous: ◦ Mycetoma: draining sinuses, tissue overgrowth, and bony destruction (Figure 3, Figure 5) ◦ Localized infections: nodules, abscesses, or granulomatous lesions • Ocular: Rare due to corneal barrier function
5. DIAGNOSTIC APPROACH¶
- Initial Assessment: Based on risk factors, clinical presentation, and imaging findings.
- Definitive Diagnosis: • Culture: Blood, sputum, or tissue • Molecular testing: NAAT
- Microscopy: • Gram stain: Identifies Gram-positive rods • Special stains: PAS, Grocott-Gomori (enhance visualization of filamentous morphology) • Morphology: Look for "beaded" chains or a "Chinese letter" pattern (Figure 8)
- Imaging: • CT: Primary modality for pulmonary disease • MRI: Preferred for CNS lesions
- Diagnostic Algorithm (Figure 9): Risk Factors → Clinical Presentation/Imaging → Microbiology (Culture/NAAT)
6. TREATMENT & MANAGEMENT¶
• Treatment Duration: ◦ General: 3–12 months depending on severity and immune status ◦ Specific Durations (Table 179-1): - Pulmonary or systemic (Intact host defenses) → 6–12 months - Pulmonary or systemic (Deficient host defenses) → 12 months - CNS disease → 12 months - Osteomyelitis, arthritis, laryngitis, sinusitis → 4 months - Keratitis: Topical until clinical cure; Systemic for 2–4 months after clinical cure • First-line Regimens: - TMP-SMX: 960 mg bid for 14 days, then maintenance - Linezolid: 600 mg bid for 12–24 weeks - Amikacin: 15 mg/kg tid for 2–4 weeks (severe cases) • Alternative Agents: - imipenem, moxifloxacin, minocycline • Surgical Intervention: - Indicated for abscess drainage or tissue necrosis• Monitoring: - Required for drug toxicity (e.g., nephrotoxicity with amikacin)
7. PROGNOSIS & PREVENTION¶
• Mortality: ◦ ~20–30% in immunocompromised patients without treatment • Prognosis Factors: ◦ Early diagnosis and adequate therapy significantly improve outcomes • Prevention: ◦ Focus on infection control in high-risk populations (transplant, CGD) ◦ No vaccine available; avoid soil exposure in at-risk individuals
8. TABLES & DIAGNOSTIC CRITERIA¶
• Differential Diagnosis: - Distinguished from other mycobacterial infections via growth characteristics and susceptibility patterns.
Table 178-1: Effective Antibiotics for the Treatment of Donovanosis
| ANTIBIOTIC | ORAL DOSE |
|---|---|
| Azithromycin | 1 g on day 1, then 500 mg daily for 7 days or 1 g weekly for 4 weeks |
| Trimethoprim-sulfamethoxazole | 960 mg bid for 14 days |
| Doxycycline | 100 mg bid for 14 days |
| Erythromycin | 500 mg qid for 14 days (pregnant women) |
| Tetracycline | 500 mg qid for 14 days |
Table 179-1: Treatment Duration for Nocardiosis
| DISEASE | DURATION |
|---|---|
| Pulmonary or systemic (Intact host defenses) | 6–12 months |
| Pulmonary or systemic (Deficient host defenses) | 12 months |
| CNS disease | 12 months |
| Osteomyelitis, arthritis, laryngitis, sinusitis | 4 months |
| Keratitis | Topical: until clinical cure; Systemic: 2–4 months after clinical cure |
Reference Tables¶
TABLE 178-1 Effective Antibiotics for the Treatment of Donovanosis ANTIBIOTIC Azithromycin…¶
Harrison's 22e, p.1358
| ANTIBIOTIC | ORAL DOSE |
|---|---|
| Azithromycin | 1 g on day 1, then 500 mg daily for 7 days or 1 g weekly for 4 weeks |
| Doxycycline | 100 mg bid for 14 days |
| Tetracycline | 500 mg qid for 14 days |
TABLE 179-1 Treatment Duration for Nocardiosis DISEASE Pulmonary or systemic¶
Harrison's 22e, p.1362
| DISEASE | DURATION |
|---|---|
| Pulmonary or systemic | |
| Intact host defenses | 6–12 months |
| Deficient host defenses | 12 monthsa |
| CNS disease | 12 monthsb |
| Osteomyelitis, arthritis, laryngitis, sinusitis |
4 months |
| Keratitis | Topical: until clinical cure |
| Systemic: until 2–4 months after clinical cure |