Gram-positiveBacilliBranching filaments

Nocardia asteroides

Partially acid-fast, branching filamentous Gram-positive aerobic bacterium causing pulmonary nocardiosis and disseminated infections, particularly in immunocompromised hosts.

Organism Card

DomainMust know
Identity
  • Aerobic actinomycete; filamentous Gram-positive bacterium
  • Branching, beaded, filamentous rods — resembles fungi morphologically
  • Weakly acid-fast (modified Ziehl-Neelsen / Kinyoun positive) — key distinguishing feature
  • Belongs to order Actinomycetales; NOT a true fungus despite filamentous growth
Lab discriminator
  • Modified (weak) acid-fast stain positive — distinguishes from Actinomyces (acid-fast negative)
  • Gram stain: branching filamentous G+ve rods
  • Aerobic growth on Sabouraud or Lowenstein-Jensen media; slow grower (2–14 days)
  • Actinomyces = anaerobic, NOT acid-fast; Nocardia = aerobic, weakly acid-fast
  • Urease positive; may partially resist decolorisation by 1% H₂SO₄
Reservoir / transmission
  • Ubiquitous soil saprophyte; found worldwide including Hong Kong
  • Inhalation of contaminated soil/dust is primary route
  • NOT person-to-person transmission
  • Percutaneous inoculation (traumatic wound, thorn prick) — causes mycetoma
  • Construction site / gardening / soil exposure = classic vignette clue [1]
Key virulence
  • Catalase and superoxide dismutase → resist oxidative killing within macrophages/neutrophils
  • Cord factor (trehalose dimycolate analogue) → impairs phagosome–lysosome fusion
  • Cell wall mycolic acids → resist intracellular killing; basis for partial acid-fastness
  • Obligate aerobe; thrives in lung tissue with high O₂ tension
Clinical syndromes
  • Pulmonary nocardiosis (most common, ~70%) — subacute/chronic pneumonia in immunocompromised; cavitary lesions on CXR [1][2]
  • CNS dissemination → brain abscess (second most common site; ~30% of disseminated cases)
  • Cutaneous/subcutaneous: mycetoma (Madura foot), lymphocutaneous sporotrichoid spread
  • Classic host: immunosuppressed — transplant recipients, chronic corticosteroids, HIV/AIDS, haematological malignancy post-chemotherapy [1][2]
  • Triad to remember: Lung + Brain + Skin in an immunocompromised patient
Diagnosis
  • Specimen: sputum, BAL, brain abscess aspirate, skin biopsy
  • Modified acid-fast stain (1% H₂SO₄) showing branching filamentous rods = key finding
  • Culture on blood agar / Sabouraud agar — hold for ≥2 weeks (slow grower)
  • Pitfall: may be dismissed as contaminant; lab must be alerted to hold cultures longer
  • MALDI-TOF MS or 16S rRNA sequencing for species-level identification [3]
Treatment
  • First-line: TMP-SMX (co-trimoxazole / Septrin) — drug of choice for all forms [1][2]
  • Alternatives / combination for severe/CNS disease: imipenem, amikacin, linezolid
  • Prolonged course required: 6–12 months (at least 6 months for pulmonary; 12 months if CNS)
  • Brain abscess may require neurosurgical drainage + prolonged antibiotics
  • Key caveat: sulfonamide resistance emerging; susceptibility testing recommended
Prevention
  • TMP-SMX prophylaxis in transplant / immunocompromised patients also covers Nocardia (as well as PJP) [1][2]
  • No vaccine available
  • Not a notifiable disease in Hong Kong
  • No isolation required (no person-to-person spread)
Classic traps
  • Nocardia vs Actinomyces: Nocardia = aerobic + weakly acid-fast + no sulfur granules; Actinomyces = anaerobic + NOT acid-fast + sulfur granules + associated with IUD/dental/jaw
  • Nocardia vs TB: both acid-fast; Nocardia is weakly/partially acid-fast (modified ZN), TB is strongly acid-fast (standard ZN with 20% H₂SO₄)
  • Nocardia vs fungal infection: filamentous morphology mimics fungi but is a bacterium — responds to antibacterials, NOT antifungals
  • Vignette discriminator: immunocompromised + cavitary lung lesion + brain abscess + weakly acid-fast branching rods = Nocardia

Exam Intelligence

  1. GC 102 (Fever after chemotherapy / infections in immunocompromised hosts): Nocardia is listed among opportunistic infections in neutropenic and cell-mediated immunodeficient patients. The lecture emphasises that pulmonary Nocardia is a key differential for abnormal lung shadow in immunocompromised patients alongside Aspergillus, PJP, CMV, and TB [1].

  2. GC 105 (Medically important microbes — what every doctor should know): Nocardia is highlighted as a weakly acid-fast aerobic actinomycete — the acid-fast property and aerobic nature are the two testable discriminators from Actinomyces [2].

  3. GC 052 (Fever and purulent sputum): Nocardia should be considered when a patient with immunosuppression presents with subacute purulent sputum and cavitary CXR changes that do not respond to standard empirical antibiotics [1].

  4. TMP-SMX dual coverage: In immunocompromised patients already on TMP-SMX prophylaxis for PJP, they are simultaneously protected against Nocardia. If prophylaxis is stopped or the patient is non-compliant, Nocardia risk rises — this is a frequently tested concept in post-transplant infection scenarios [1][2].

  5. Jerry's immunodeficiencies (Senior notes): Chronic granulomatous disease (CGD) patients are susceptible to catalase-positive organisms; Nocardia is catalase-positive and can cause disease in CGD, though Staphylococcus and Aspergillus are more classic [4].

  6. Modified acid-fast staining: The distinction between standard ZN (20% H₂SO₄ — for Mycobacteria) and modified ZN (1% H₂SO₄ — for Nocardia) is a classic MCQ discriminator. Nocardia loses staining with strong acid but retains it with weak acid [3].

  • Nocardia vs Actinomyces — the single most common exam trap:
FeatureNocardiaActinomyces
Oxygen requirementAerobicAnaerobic
Acid-fastWeakly positive (modified ZN)Negative
Sulfur granulesAbsentPresent
Classic siteLung → brain (immunocompromised)Cervicofacial / pelvic (IUD)
TreatmentTMP-SMXPenicillin / amoxicillin
  • Nocardia vs Rhodococcus equi: Both are aerobic, partially acid-fast, and cause pulmonary disease in immunocompromised. Rhodococcus = coccobacillus (not filamentous), classically in HIV with horse/farm exposure.

  • Nocardia vs Aspergillus: Both cause cavitary lung disease and can disseminate to brain in immunocompromised. Nocardia = bacterium (responds to TMP-SMX); Aspergillus = fungus (responds to voriconazole/amphotericin). Gram stain and modified acid-fast stain differentiate.

  • "Branching filamentous rods" in sputum of an immunocompromised patient = Nocardia until proven otherwise.

  • Brain abscess differential in immunocompromised: Nocardia (weakly acid-fast branching rods), Toxoplasma (ring-enhancing, HIV), Aspergillus (fungal hyphae), TB (caseating granuloma).

2021 Fourth Summative SAQ Q12 [5]:

"A 40-year-old man had bone marrow transplant for chronic myeloid leukaemia. ... (b) On day 28 after neutrophil engraftment, he developed fever, impaired liver function test, persistent diarrhoea and chest X-ray infiltrates. The patient admitted that he did not take the antimicrobial prophylaxis which was prescribed. List 四 organisms which may account for his symptoms."

  • Correct answer / markscheme: The question asks for 4 organisms in a post-BMT patient who stopped prophylaxis (likely TMP-SMX). Expected answers include CMV (reactivation causing colitis, hepatitis, pneumonitis), PJP (Pneumocystis jirovecii — CXR infiltrates, no prophylaxis), Nocardia (lung infiltrates, not taking TMP-SMX prophylaxis), and Aspergillus (pulmonary infiltrates post-engraftment).
  • Discriminator: The vignette's key clue is "did not take antimicrobial prophylaxis" — TMP-SMX prophylaxis covers both PJP and Nocardia. Non-compliance unmasks risk for both. This is a classic exam hook tying Nocardia to the immunocompromised host and TMP-SMX prophylaxis [1][5].

No other directly Nocardia-specific past paper questions were identified in the indexed past papers.

[1] Lecture slides: GC 102. Fever after chemotherapy infections in immunocompromised hosts.pdf [2] Lecture slides: GC 105. Medically important microbes what every doctor should know.pdf [3] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf [4] Senior notes: Jerry's immunodeficiencies.pdf [5] Past papers: 2021 Fourth Summative SAQ.pdf

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