Nocardiosis

Epidemiology

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

Risk Factors

  • Defect in T-Cell Mediated Immunity: main risk factor
  • Granulocyte Defects: lesser risk factor
  • Immunoglobulin Defects: lesser risk factor
  • No Known Risk Factors: 50% of Nocardia cases have no known risk factors

Microbiology

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

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, [[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

Clinical Manifestations

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


Prevention

  • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) Prophylaxis (see Sulfamethoxazole-Trimethoprim, [[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

Treatment

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

Prognosis

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

References

  • Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994 Apr;7(2):213-64 [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]