Nocardia

Background

Microbiology

• Beaded Gram-positive partially acid-fast bacillus within the class Actinobacteria and order Corynebacteriales
• Catalase positive and lyzozyme resistant
• Has a classic beaded branching cell morphology
• Microscopic appearance similar to Actinomyces, differentiated by acid fast staining (Actinomyces is not acid fast)
• Colonies are slow to grow and have a chalky white appearance
• Ubiquitous environmental saprophyte found in soil and water

Pathophysiology

• Spores or mycelia are either inhaled into the lungs or directly inoculated in the skin and soft tissue
• Traumatic inoculation includes during motor vehicle collisions, mild scratches or pricks, or nosocomial with dirt entering through an open wound or central line
• Forms difficult-to-treat biofilms when involved in CLABSIs

Risk Factors

• More common in immunocompromised (cell-mediated immunodeficiency including HIV, hematologic malignancy, and transplant patients), though can also occur in immunocompetent who have COPD, bronchiectasis, and cystic fibrosis
• Among transplant recipients, lung transplant appears to be highest risk
• High-dose steroids and high levels of calcineurin inhibitors appear to be specific risk factors
• Also diabetes and alcohol use

Clinical Manifestations

Primary Cutaneous

• Typically acquired by direct inoculation with soil
• Nocardia brasiliensis is the most common cause in North America
• May present with superficial soft tissue infection, including ulcer, abscess, cellulitis, pustules, plaques, or papules, most commonly on the arms and legs
• Can progress to lymphocutaneous infection with sporotrichoid lesions

Pulmonary

• Subacute or chronic cough, dyspnea, fever, with or without pleuritic chest pain
• Most common form of disease in US
• Colonization also possible, particularly with patients who have structural lung changes like cystic fibrosis
• Starts with inflammation followed by formation of granulomas and necrotic abscesses
• Imaging typically showed lung nodules, lobar consolidation, and pleural effusion, and may show infiltrates and necrotizing granulomas
  • Usually bilateral
  • Cavitations more common in immunocompromised patients

Disseminated

• Usually starts with a focal infection (skin or lung), which then disseminates hematogenously
• Most commonly involves skin, lungs, and CNS, but can also disseminate to kidney, joint, retina, and heart
• Much more common in immunosuppressed patients

CNS Disease

• Most common site of hematogenous dissemination
• Presents with typical symptoms of fever, headache, meningismus, seizure, and focal neurologic deficits
• Can also be asymptomatic, so immunocompromised patients should get imaging and possibly LP

Other

• Mycetoma
• Bacteremia
• Ocular infection, either from direct inoculation or hematogenous spread
• Bone and joint infection, primarily from dissemination

Management

Further Evaluation

• Consider screening MRI brain in all patients with disseminated or pulmonary disease regardless of neurologic symptoms
• Consider CT chest in all patients
• Consider assessment for immunodeficiency; at the very least, HIV testing and a good history

Antimicrobial Selection

• Mild to moderate: TMP-SMX
  • Immunocompetent: 5-10 mg/kg split tid to qid
  • Immunocompromised: 15 mg/kg split tid to qid
• Severe: TMP-SMX plus either amikacin or imipenem
• Other antimicrobials include ceftriaxone, minocycline, and linezolid

Duration

• Isolated cutaneous infection in immunocompetent host: 3 to 6 months
• Isolated cutaneous infection in immunocompromised host: 6 to 12 months
• Serious pulmonary infection: 6 to 12 months or longer
• Any non-cutaneous disease in immunocompromised host: at least 12 months, and possibly lifelong suppression

Monitoring

• Serial CT scans to assess response to therapy
• Monitoring for antibiotic toxicity