Nocardiosis¶
Chapter 179 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Nocardiosis is an opportunistic infection caused by Nocardia species, primarily affecting immunocompromised individuals with host defense defects.
- Key antibiotics include trimethoprim-sulfamethoxazole (TMP-SMX), linezolid, amikacin, and imipenem/meropenem, with treatment duration varying by disease type.
- CNS involvement is common (up to 2/3 of disseminated cases), often presenting with brain abscesses and requiring MRI/CT for diagnosis.
- Actinomycetoma (N. brasiliensis) presents with chronic granulomatous inflammation, sinus tracts, and granules, often in tropical regions.
- Diagnosis relies on acid-fast staining, culture on specialized media, and prolonged incubation, with surgical drainage for abscesses.
1. DEFINITION & OVERVIEW¶
Nocardiosis is an infection caused by Nocardia species, Gram-positive aerobic filamentous bacteria. It occurs primarily in immunocompromised hosts, with pulmonary, cutaneous, and CNS manifestations. The disease is classified as a rare, opportunistic infection with variable clinical presentations.
Table 178-1: Effective Antibiotics for 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 |
1.1 Pathogenesis¶
Nocardiae enter via inhalation or trauma, surviving in phagocytes by neutralizing oxidants and preventing phagolysosome fusion. Immunosuppression (e.g., HIV, transplant recipients) increases susceptibility. N. farcinica is the most common CNS pathogen.
1.2 Clinical Forms¶
Pulmonary (most common), cutaneous (trauma-related), CNS (brain abscesses), and ocular (keratitis, endophthalmitis). Actinomycetoma involves subcutaneous granules and sinus tracts.
2. EPIDEMIOLOGY¶
Global incidence ~0.375 cases/100,000/year. More common in adults, males, and immunocompromised individuals (e.g., HIV, transplant recipients, corticosteroid users). Risk factors include soil/vegetable exposure, poor hygiene, and underlying immunodeficiency.
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 |
| Primary cutaneous disease (cellulitis, lymphocutaneous) | 2 months |
| Osteomyelitis, arthritis, sinusitis | 4 months |
| Actinomycetoma | 6–12 months |
| Keratitis | Topical: until clinical cure; Systemic: until 2–4 months after clinical cure |
2.1 Demographics¶
Predominantly affects adults, with higher prevalence in males. Actinomycetoma is endemic in tropical/subtropical regions (Mexico, Sudan, India).
2.2 Risk Factors¶
Immunosuppression (HIV, organ transplant, corticosteroids), solid organ transplantation, neutropenia, and chronic granulomatous disease (CGD).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Nocardia species (over 50 pathogenic species) are soil saprophytes with mycolic acid-rich cell walls. They resist phagocytosis and survive in macrophages. N. farcinica is most common in CNS infections. Resistance to antibiotics varies by species (e.g., N. transvalensis is resistant to amikacin).
Table 179-1: Nocardia Species Susceptibility¶
| SPECIES | ANTIBIOTIC SUSCEPTIBILITY |
|---|---|
| N. farcinica | Sensitive to TMP-SMX, imipenem, meropenem |
| N. brasiliensis | Responsive to TMP-SMX, linezolid |
| N. transvalensis | Resistant to amikacin, TMP-SMX |
| N. abscessus complex | Resistant to TMP-SMX; sensitive to amikacin, linezolid |
3.1 Species Susceptibility¶
N. farcinica: sensitive to TMP-SMX, imipenem, and meropenem. N. brasiliensis: responds to TMP-SMX and linezolid. N. transvalensis: resistant to amikacin and TMP-SMX.
3.2 Immune Evasion¶
Nocardiae neutralize oxidants, prevent phagolysosome fusion, and resist killing by neutrophils. Autoantibodies to GM-CSF are linked to pulmonary alveolar proteinosis and nocardiosis.
4. CLINICAL FEATURES¶
Pulmonary: subacute onset with cough, fever, and infiltrates. CNS: brain abscesses (60–70% of disseminated cases). Cutaneous: cellulitis, lymphocutaneous syndrome, or actinomycetoma. Ocular: keratitis, endophthalmitis. Actinomycetoma: chronic granulomatous inflammation with sinus tracts and granules.
4.1 Pulmonary Manifestations¶
Infiltrates, nodules, cavities, and pleural effusions. Bronchiectasis may coexist. Fever, weight loss, and hemoptysis are common.
4.2 CNS Involvement¶
Brain abscesses (multiloculated, ring-enhancing on MRI). Meningitis is rare, typically secondary to abscess rupture. N. farcinica is most common CNS pathogen.
5. DIFFERENTIAL DIAGNOSIS¶
Sporothrix schenckii (cutaneous), Mycobacterium marinum (skin), fungal infections (eumycetoma), and bacterial abscesses. Actinomycetoma must be distinguished from eumycetoma (fungal) and botryomycosis (Staphylococcus).
5.1 Key Differentiators¶
Nocardia: acid-fast filaments, branching morphology. Sporothrix: yeast-like, hyaline hyphae. Fungal mycetoma: granules with fungal elements. Bacterial abscesses: no granules.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis via acid-fast staining (Kinyoun, Fite-Faraco), culture on specialized media (colistin-nalidixic agar), and imaging (MRI/CT for CNS). Bronchoalveolar lavage or biopsy for pulmonary cases. Susceptibility testing required for complex species.
6.1 Diagnostic Methods¶
Sputum/pus smear: branching, beaded Gram-positive filaments (1–50 µ m). Culture: 2–4 weeks for growth. MRI/CT: ring-enhancing brain abscesses. Histology: pyogranulomatous inflammation.
6.2 Laboratory Testing¶
MALDI-TOF or 16S rRNA sequencing for speciation. Susceptibility testing: avoid decontamination steps for nocardia. E-test less reliable due to clumping.
7. MANAGEMENT & TREATMENT¶
Combination therapy (TMP-SMX, linezolid, amikacin, imipenem/meropenem) for severe cases. Duration: 6–12 months for pulmonary/systemic, 12 months for CNS. Surgery for abscesses or actinomycetoma. Avoid corticosteroids in keratitis.
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 |
| Primary cutaneous disease (cellulitis, lymphocutaneous) | 2 months |
| Osteomyelitis, arthritis, sinusitis | 4 months |
| Actinomycetoma | 6–12 months |
| Keratitis | Topical: until clinical cure; Systemic: until 2–4 months after clinical cure |
7.1 Antibiotic Regimens¶
TMP-SMX (first-line), linezolid (CNS), amikacin (resistant strains), imipenem/meropenem (CNS). Doses: TMP 10–20 mg/kg, SMX 50–100 mg/kg, linezolid 600 mg q8h.
7.2 Surgical Management¶
Abscess drainage/aspiration, excision for actinomycetoma. Avoid corticosteroids in keratitis. Monitor for relapse after treatment.
8. PROGNOSIS & COMPLICATIONS¶
Localized nocardiosis: <10% mortality. Disseminated disease (CNS involvement): higher mortality. Complications include brain abscesses, empyema, and chronic disability from actinomycetoma. CGD patients require screening for nocardiosis.
8.1 Mortality¶
Localized: <10%. Disseminated: 20–40% mortality. CNS involvement: 50–70% mortality if untreated.
8.2 Long-term Effects¶
Chronic disability, disfigurement, and stigmatization from actinomycetoma. Prolonged immunosuppression increases recurrence risk.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: avoid tetracyclines; use TMP-SMX. Pediatrics: monitor for CGD. Elderly: adjust dosages for renal function. HIV patients: require prolonged therapy. Avoid corticosteroids in keratitis.
9.1 Pregnancy¶
Avoid tetracyclines; use TMP-SMX or linezolid. Monitor for fetal effects.
9.2 Immunosuppressed Patients¶
Prolonged therapy (12 months) and susceptibility testing required. Monitor for relapse.
10. KEY POINTS & CLINICAL PEARLS¶
- Use TMP-SMX as first-line for most nocardiosis. 2. CNS involvement requires MRI/CT and prolonged therapy. 3. Actinomycetoma is chronic, requiring surgical drainage. 4. Avoid corticosteroids in keratitis. 5. Monitor for relapse in immunocompromised patients.