Epidemiology

• Immunosuppression: 50% of Nocardia cases occur in immunosuppressed hosts

Risk Factors

• Defect in T-Cell Mediated Immunity: main risk factor
  • Corticosteroids (see Corticosteroids)
  • Cushing Syndrome (see Cushing Syndrome)
  • Human Immunodeficiency Virus (HIV)/AIDS (see Human Immunodeficiency Virus,)
  • Immunosuppression
  • Lymphoreticular Malignancies
  • Pulmonary Alveolar Proteinosis (PAP) (see Pulmonary Alveolar Proteinosis)
• Granulocyte Defects: lesser risk factor
  • Chronic Granulomatous Disease (CGD) (see Chronic Granulomatous Disease)
• Immunoglobulin Defects: lesser risk factor
• No Known Risk Factors: approximately 50% of Nocardia cases have no known risk factors

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Microbiology

Nocardia Species

• Nocardia Asteroides: accounts for 80% of Nocardiosis cases
• Nocardia Brasiliensis and Other Species (Nocardia Otitidiscaviarum, Nocardia Nova, Nocardia Farcinica, etc): account for 20% of Nocardiosis cases

Taxonomy

• Genus Nocardia is a Member of Family Actinomycetaceae (Colloquially Termed “Actinomycetes”) (see Actinomycetaceae)
  • All of the Actinomycetes Organisms are Morphologically Similar and Exhibit Characteristic Filamentous Branching with Fragmentation into Bacillary or Coccoid Forms

Origin

• Nocardia Exists Ubiquitously in Nature as a Soil Contaminant

Features

• Gram-Positive, Beaded, Branching Filamentous Rod
  • Nocardia Stains Weakly Acid-Fast
  • Nocardia Requires Aerobic Growth Conditions: in contrast, Actinomyces requires anaerobic growth conditions (see Actinomycosis)
  • Nocardia Can Be Grown on Standard Culture Medium (Blood Agar or Sabouraud’s): however, growth may not be apparent for 3-21 days

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Physiology

• Portals of Nocardia Infection
  • Respiratory Tract
  • Skin
  • Gastrointestinal Tract
• Local Extension: Nocardia extends from lung to pleural space (with or without chest wall involvement) in 10% of cases
• Comparison with Actinomyces (see Actinomycosis)
  • Both Nocardiosis and Actinomycosis Occur in Healthy and Immunosuppressed Hosts
  • Nocardia has Lesser Propensity for Sinus Tract Formation than Actinomyces
  • Nocardia has Greater Propensity for Dissemination than Actinomyces

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Clinical Manifestations

Pulmonary Manifestations

Segmental or Lobar Pneumonia (see Pneumonia)

• Epidemiology
  • Symptoms May Be Present for Weeks Prior to Presentation
  • Immunosuppressed Patients May Have Fulminant Presentation
• Diagnostic
  • Sputum Gram Stain/Culture and Sensitivity (see Sputum Culture): although Nocardia frequently colonizes the respiratory tract, culturing the organism from sputum is highly predictive of infection
  • Bronchoscopy (see Bronchoscopy)
    • Useful to Obtain DIagnostic Specimens (and Rule Out Any Component of Endobronchial Disease)
• Clinical
  • Fatigue (see Fatigue)
  • Low-Grade Fever (see Fever)
  • Night Sweats (see Night Sweats)
  • Pleuritic Chest Pain (see Chest Pain)
  • Productive Cough (see Cough)
  • Weight Loss (see Weight Loss)
• Treatment
  • Early Treatment May Prevent Cavitation and Dissemination

Solitary or Multiple Lung Nodules Which May Cavitate (see Lung Nodule or Mass and Cystic-Cavitary Lung Lesions)

• Diagnosis
  • Chest X-Ray (CXR)/Chest Computed Tomography (CT) (see Chest X-Ray and Chest Computed Tomography): nodules may cavitate

Endobronchial Lesions (with/without Pneumonia)

• Epidemiology
  • There are Case Reports of Endobronchial Nocardiosis (Eur Respir J, 1994) [MEDLINE] (Mt Sinai J Med, 2006) [MEDLINE]
• Diagnosis
  • Bronchoscopy (see Bronchoscopy)

Lung Abscess (see Lung Abscess)

• Epidemiology
  • Occurs in Some Cases
• Diagnosis
  • Suppurative (Non-Granulomatous)

Interstitial Pneumonia/Miliary Infiltrates (see Interstitial Lung Disease)

• Epidemiology
  • Occurs in Some Cases

Pleural Effusion (see Pleural Effusion-Exudate)

• Epidemiology: occurs in 50% of Nocardia cases (almost always in association with parenchymal infiltrates)
• Diagnosis
  • Pleural Fluid
    • Appearance: ranges from serous fluid to frank pus
    • Aerobic Culture: culture may be positive or negative (grows slowly, may take up to 3 weeks to grow out)

Disseminated Nocardiosis

Dermatologic Manifestations

• Subcutaneous Skin Abscess with/without Sinus Tract (see Skin Abscess)
  • Diagnosis: suppurative (non-granulomatous)

Neurologic Manifestations

• Brain Abscess (see Brain Abscess)

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Prevention

• Sulfamethoxazole-Trimethoprim (Bactrim, Septra) Prophylaxis (see Sulfamethoxazole-Trimethoprim): daily prophylaxis decreases the risk of Nocardiosis
  • Intermittent Prophylaxis (2 DS Tablets Twice Per Week or 1 SS Tablet 3x Per Week) is Less Protective Against Nocardiosis

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Treatment

Antibiotics

Treatment of Choice

• Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim)
  • Administration: 5-10 mg/kg/day of trimethoprim component (or 25-50 mg/kg/day of sulfamethoxazole component)
  • Sulfonamides are Bacteriostatic
  • Good Central Nervous System Penetration
  • Susceptibility Testing Should be Performed
    • Nocardia Otitidiscaviarum is commonly resistant to Sulfamethoxazole-Trimethoprim
    • Nocardia Nova and Nocardia Farcinica are occasionally resistant to Sulfamethoxazole-Trimethoprim

Alternative Antibiotics

• Amikacin (Amikin) (see Amikacin)
• Cephalosporins (see Cephalosporins)
  • Cefotaxime (Claforan, Cefatam) (see Cefotaxime)
  • Ceftriaxone (Rocephin) (see Ceftriaxone)
    • Good Central Nervous System Penetration
• Carbapenems (see Carbapenems)
  • Imipenem (Primaxin) (see Imipenem): most active carbapenem against Nocardia
    • Ertapenem (Invanz) (see Ertapenem): should not be used as a replacement for imipenem or meropenem
  • Meropenem (Merrem) (see Meropenem)
• Linezolid (Zyvox) (see Linezolid)
  • Active Against Virtually All Known Nocardia Species
  • Has Been Successfully Used to Treat Disseminated and Central Nervous System Nocardiosis
• Moxifloxacin (Avelox) (see Moxifloxacin)
  • Fairly Active In Vitro Against Nocardia Astroides Complex
• Tetracyclines (see Tetracyclines)
  • Minocycline (Minocin) (see Minocycline): has the best activity of the tetracyclines against Nocardia
• Tigecycline (Tygacil) (see Tigecycline)
  • Has In Vitro Activity Against Most Nocardia Species

Combination Therapy

• General Comments
  • Combination Therapy May Provide Enhanced Activity: recommended as initial therapy with de-escalation to a single agent (as dictated by clinical response)
• Imipenem + Cefotaxime
• Amikacin + Sulfamethoxazole-Trimethoprim
• Imipenem + Sulfamethoxazole-Trimethoprim
• Imipenem + Amikacin

Duration of Therapy

• Immunocompetent Patients with Isolated Pulmonary or Non-Central Nervous System Multifocal Nocardiosis: 6-12 mo
• Immunosuppressed Patients: ≥12 mo

Drainage of Abscesses/Empyema

• Required

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Prognosis

• Mortality Rate: near 50% in those with CNS disease
• Mortality Rate: <10% in those with only pulmonary disease

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References

• Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994 Apr;7(2):213-64 [MEDLINE]
• Endobronchial nocardiosis. Eur Respir J. 1994 Oct;7(10):1903-5. doi: 10.1183/09031936.94.07101903 [MEDLINE]
• Endobronchial pulmonary nocardiosis. Mt Sinai J Med. 2006 May;73(3):617-9 [MEDLINE]
• Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012 Apr;87(4):403-7. doi: 10.1016/j.mayocp.2011.11.016 [MEDLINE]
• Current treatment for nocardia infections. Expert Opin Pharmacother. 2013 Dec;14(17):2387-98. doi: 10.1517/14656566.2013.842553. Epub 2013 Oct 4 [MEDLINE]
• Experience with linezolid for the treatment of nocardiosis in organ transplant recipients. J Infect. 2015 Jan;70(1):44-51. doi: 10.1016/j.jinf.2014.08.010. Epub 2014 Aug 30 [MEDLINE]