Risk Factors

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

Nocardia Species (in the Order Actinomycetes)

• 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

Aerobic Organisms in the Order Actinomycetes

• General Comments
  • All of the Actinomycetes Organisms Can Exhibit Filamentous Branching with Fragmentation into Coccoid Forms
• Corynebacteria (see Corynebacteria)
• Mycobacteria (see Mycobacteria)
• Nocardia
• Rhodococcus (see Rhodococcus)
• Streptomycetes (see Streptomycetes)

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, [[Actinomycosis]])
  • Nocardia Can Be Grown on Standard Culture Medium (Blood Agar or Sabouraud’s): however, growth may not be apparent for 3-21 days

Pulmonary Manifestations

Segmental or Lobar Pneumonia (see Pneumonia, [[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, [[Sputum Culture]]): although Nocardia frequently colonizes the respiratory tract, culturing the organism from sputum is highly predictive of infection
• Clinical
  • Fatigue (see Fatigue, [[Fatigue]])
  • Low-Grade Fever (see Fever, [[Fever]])
  • Night Sweats (see Night Sweats, [[Night Sweats]])
  • Pleuritic Chest Pain (see Chest Pain, [[Chest Pain]])
  • Productive Cough (see Cough, [[Cough]])
  • Weight Loss (see Weight Loss, [[Weight Loss]])
• Treatment
  • Early Treatment May Prevent Cavitation and Dissemination

Solitary or Multiple Lung Nodules (see Lung Nodule or Mass, [[Lung Nodule or Mass]] and Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])

• Diagnosis
  • CXR/Chest CT: nodules may cavitate

Lung Abscess (see Lung Abscess, [[Lung Abscess]])

• Epidemiology: occurs in some cases
• Diagnosis: suppurative (non-granulomatous)

Interstitial Pneumonia/Miliary Infiltrates (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

• Epidemiology: occurs in some cases

Pleural Effusion (see Pleural Effusion-Exudate, [[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, [[Skin Abscess]])
  • Diagnosis: suppurative (non-granulomatous)

Neurologic Manifestations

• Brain Abscess (see Brain Abscess, [[Brain Abscess]])

Antibiotics

Treatment of Choice

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