MUCORMYCOSIS (ZYGOMYCOSIS)

🔹 Etiology

Causative fungi (Order Mucorales):

  • Rhizopus species (most common, especially Rhizopus arrhizus)
  • Mucor
  • Lichtheimia (formerly Absidia)
  • Apophysomyces (especially in India, causes cutaneous mucormycosis)

🔹 Epidemiology

  • Ubiquitous in soil, decaying organic matter.
  • Spores are transmitted via inhalation, ingestion, or inoculation into disrupted skin/mucosa.
  • Opportunistic infection — occurs mainly in immunocompromised or metabolically deranged hosts.

🔹 Predisposing Conditions

Predisposing Factor

Mechanism

Uncontrolled diabetes mellitus (especially DKA)

Elevated glucose and acidic pH reduce phagocytic function, increase free iron for fungal growth

Hematologic malignancy / HSCT / neutropenia

Impaired neutrophil function

Solid organ transplantation

Immunosuppressive therapy

Prolonged corticosteroid therapy

Impaired macrophage and neutrophil function

Iron overload / Deferoxamine therapy

Fungi use deferoxamine as siderophore (“iron shuttle”)

Severe trauma / burns / COVID-19

Direct inoculation, tissue hypoxia

Malnutrition, Prematurity (neonatal GI mucormycosis)

Reduced host defenses

🔹 Pathogenesis

  1. Spore inoculation → inhalation, ingestion, or direct implantation.
  2. Angioinvasion → hyphae invade vessel walls → thrombosis, ischemic necrosis, and black eschar.
  3. Rapid tissue destruction → contiguous spread (e.g., from sinuses to orbit and brain).

Characteristic morphology:

  • Broad, ribbon-like, non-septate hyphae (6–25 µm)
  • Irregular right-angle branching

🔹 Clinical Forms

Type

Common Site

Clinical Features

1. Rhinoorbital-cerebral (ROCM)

Paranasal sinuses, orbit, brain

Facial pain/swelling, nasal congestion, black eschar on nasal/palatal mucosa, ophthalmoplegia, ptosis, proptosis, headache, cranial nerve palsies, cavernous sinus thrombosis

2. Pulmonary

Lungs

Fever, cough, hemoptysis, pleuritic pain, rapidly progressive necrotizing pneumonia (common in neutropenia)

3. Cutaneous

Skin, wound

Necrotic ulcer with black eschar; may follow trauma, burns, or contaminated dressings

4. Gastrointestinal

Stomach, colon

Occurs in malnourished or premature infants; abdominal pain, GI bleeding, perforation

5. Disseminated

Multiorgan

Secondary to hematogenous spread; CNS, heart, spleen, kidney involvement

🔹 Diagnostic Evaluation

1. Clinical suspicion:
Rapidly progressive necrosis (especially black eschar) in high-risk host = red flag.

2. Imaging:

  • CT / MRI of sinuses/orbit/brain:
    • Sinus opacification with bone erosion
    • Orbital infiltration, cavernous sinus involvement
    • MRI: “Black turbinate sign” = devitalized nasal mucosa (non-enhancing)
  • CT Chest (pulmonary):
    • Consolidation, cavitation, or reverse halo sign (ground-glass center with rim of consolidation)

3. Laboratory:

  • Leukocytosis, hyperglycemia, acidosis (in diabetics)
  • No serologic test or antigen test (unlike Aspergillus)

4. Microbiology:

  • KOH mount / Calcofluor white stain: Broad aseptate hyphae
  • Culture on Sabouraud agar: Cottony white-gray colonies
  • Histopathology (gold standard):
    • Broad, non-septate hyphae with right-angle branching
    • Angioinvasion, tissue necrosis

5. Molecular tests:

  • PCR assays (under evaluation)
  • Metagenomic sequencing (research use)

🔹 Differential Diagnosis

Feature

Mucormycosis

Aspergillosis

Hyphae

Broad, non-septate, right-angle branching

Narrow, septate, acute-angle branching

Common host

Diabetes (DKA)

Neutropenia, transplant

Growth

Rapid

Moderate

Antigen test

Negative

Galactomannan positive

Site predilection

Sinus, orbit, brain

Lung, sinus

Iron/deferoxamine

Risk factor

Not a risk factor

🔹 Treatment

1. Urgent combined therapy:

  • Prompt antifungal therapy
  • Aggressive surgical debridement
  • Correction of underlying condition

A. Antifungal Therapy

Drug

  

Notes

Liposomal Amphotericin     B(preferred)

Start immediately; mainstay of therapy

Amphotericin B lipid complex

\Alternative if liposomal unavailable

Amphotericin B deoxycholate

Only if lipid formulation not available; nephrotoxic

Posaconazole (delayed release tab/suspension)

Step-down or salvage

Isavuconazole

As effective as amphotericin in some studies (SECURE trial)

❗ Voriconazole is ineffective against Mucorales.

B. Surgical Management

  • Early, repeated debridement of necrotic tissue until viable margins.
  • Orbital exenteration may be needed in extensive ROCM.
  • Sinus irrigation with amphotericin (topical instillation) may aid local control.

C. Correction of Predisposing Factors

  • Control hyperglycemia and ketoacidosis
  • Discontinue steroids and deferoxamine
  • Treat neutropenia (G-CSF if indicated)
  • Minimize immunosuppression

D. Adjunctive Therapy (Experimental)

  • Hyperbaric oxygen: may improve local oxygenation and neutrophil function (limited evidence)

🔹 Prognosis

Form

Mortality

Rhino-orbital-cerebral

30–50%

Pulmonary

50–70%

Gastrointestinal

85–90%

Disseminated

>90%

Mortality is reduced significantly with early diagnosis and combined surgical + antifungal therapy.

🔹 COVID-19–Associated Mucormycosis (CAM)

  • Surge during COVID-19 pandemic in India (2020–2021)
  • Risk factors:
    • Uncontrolled diabetes
    • Excessive corticosteroids
    • Hypoxia, prolonged hospitalization
  • Predominantly rhino-orbital-cerebral type
  • Public health importance: “Black fungus epidemic”

🔹 References

  1. Harrison’s Principles of Internal Medicine, 21st ed., Ch. 182.
  2. IDSA Guidelines for Mucormycosis (2019).
  3. UpToDate: “Treatment and prevention of mucormycosis.”
  4. Cornely OA et al. Clin Microbiol Infect. 2019;25(Suppl 2):S63–S119.
  5. Prakash H, Chakrabarti A. Clin Microbiol Infect 2021;27(1):10–19 (COVID-associated mucormycosis).