Mucorales

These fungi are often rapidly growing and can cause serious, life-threatening infections, especially in immunocompromised individuals. Because of their aggressive nature, timely diagnosis and treatment are essential. We’ll cover the key genera – Mucor and Rhizopus – along with their disease states, transmission, and lab identification methods

Mucorales (Zygomycetes)

• Definition: Mucorales are a group of filamentous fungi belonging to the subphylum Mucoromycotina (formerly Zygomycetes)
• Rapid Growth: They are characterized by rapid growth and the ability to cause invasive infections, particularly in immunocompromised individuals
• Hyphae: They have broad, ribbon-like hyphae that are typically non-septate or sparsely septate (meaning they have few or no cross-walls)
• Rhizoids: Some genera (e.g., Rhizopus) produce rhizoids, which are root-like structures that anchor the fungus to the substrate
• Sporangia: They reproduce asexually by forming sporangia, which are sac-like structures containing spores
• Disease: Infections caused by Mucorales are collectively known as mucormycosis (formerly zygomycosis)
• Key Genera: The most common genera causing human infections are Rhizopus, Mucor, Lichtheimia (formerly Absidia), Cunninghamella, and Apophysomyces

Rhizopus spp.

• Etiology: Rhizopus is the most common genus of Mucorales causing human infections
• Epidemiology
  • Found worldwide in soil, decaying organic matter, and food
  • Infections are acquired through inhalation of spores, ingestion of contaminated food, or direct inoculation into the skin
  • Risk factors:
    • Uncontrolled diabetes mellitus (especially diabetic ketoacidosis)
    • Immunosuppression (e.g., hematopoietic stem cell transplantation, solid organ transplantation, chemotherapy)
    • Trauma
    • Burns
    • Neutropenia
    • Deferoxamine therapy (an iron-chelating agent)
• Transmission
  • Inhalation of spores from the environment
  • Ingestion of contaminated food
  • Direct inoculation into the skin or mucous membranes
• Disease States
  • Rhino-Orbito-Cerebral Mucormycosis (ROCM): The most common form of mucormycosis, involving the sinuses, orbit (eye socket), and brain. Symptoms include facial pain, headache, fever, nasal congestion, vision changes, and mental status changes
  • Pulmonary Mucormycosis: Infection of the lungs. Symptoms include cough, fever, chest pain, and shortness of breath
  • Cutaneous Mucormycosis: Infection of the skin, often at the site of trauma or burns. Presents as necrotic ulcers or cellulitis
  • Gastrointestinal Mucormycosis: Infection of the gastrointestinal tract, typically in premature infants or malnourished individuals
  • Disseminated Mucormycosis: Spread of the infection to multiple organs, including the brain, heart, and kidneys
• Laboratory Diagnosis
  • Specimen Collection
    • Tissue Biopsy: From the affected site (e.g., sinuses, lungs, skin)
    • Bronchoalveolar Lavage (BAL): For suspected pulmonary infection
    • Sputum: Less reliable than tissue biopsy or BAL
    • Blood Cultures: Rarely positive
  • Direct Microscopic Examination
    • KOH Preparation or Gram Stain: Of tissue samples to visualize broad, ribbon-like hyphae that are typically non-septate or sparsely septate
    • GMS (Gomori Methenamine Silver) or PAS (Periodic Acid-Schiff) Stain: Of tissue biopsies to highlight fungal elements
  • Culture
    • Inoculation onto Sabouraud Dextrose Agar (SDA) or other fungal media
    • Rapid growth at 25-30°C, forming cottony, white to gray colonies that fill the Petri dish within a few days
  • Identification
    • Colony Morphology: Rapid growth and cottony texture
    • Microscopic Examination: Identification of characteristic sporangia and rhizoids
    • Rhizopus species have rhizoids that originate at the point where the stolon (horizontal hypha) connects to the sporangiophore (the stalk that bears the sporangium)
    • Molecular Methods: PCR and sequencing for definitive identification

Mucor spp.

• Etiology: Mucor is another genus of Mucorales that can cause mucormycosis, although less frequently than Rhizopus
• Epidemiology
  • Found worldwide in soil, decaying organic matter, and air
  • Infections are acquired through inhalation of spores or direct inoculation into the skin
  • Risk factors are similar to those for Rhizopus infections
• Transmission
  • Inhalation of spores from the environment
  • Direct inoculation into the skin or mucous membranes
• Disease States
  • Similar to Rhizopus, including rhino-orbito-cerebral, pulmonary, cutaneous, and disseminated mucormycosis
• Laboratory Diagnosis
  • Specimen Collection: Similar to Rhizopus
  • Direct Microscopic Examination: Similar to Rhizopus
  • Culture: Similar to Rhizopus, with rapid growth and cottony colonies
  • Identification
    • Colony Morphology: Rapid growth and cottony texture
    • Microscopic Examination: Identification of characteristic sporangia. Mucor species lack rhizoids
    • Molecular Methods: PCR and sequencing for definitive identification

Laboratory Procedures: Key Steps

• Specimen Collection
  • Collect tissue biopsies from the affected site whenever possible
  • Obtain sufficient tissue for both histopathology and culture
• Direct Microscopic Examination
  • Prepare a KOH mount or Gram stain of tissue samples
  • Examine under a microscope for broad, ribbon-like hyphae that are typically non-septate or sparsely septate
• Culture
  • Inoculate the specimen onto Sabouraud Dextrose Agar (SDA) or other fungal media
  • Incubate at 25-30°C
  • Examine regularly for rapid growth
• Identification
  • Identify fungal isolates based on macroscopic (colony morphology) and microscopic characteristics (e.g., presence or absence of rhizoids, sporangial morphology)
  • Molecular methods (PCR, sequencing) are increasingly used for rapid and accurate identification

Treatment and Prognosis

• Aggressive Treatment: Mucormycosis is a rapidly progressive and often fatal infection, requiring aggressive treatment
• Surgical Debridement: Surgical removal of infected tissue is essential
• Antifungal Therapy: Amphotericin B (especially liposomal amphotericin B) is the primary antifungal drug used to treat mucormycosis. Isavuconazole and posaconazole are alternative options
• Control of Underlying Conditions: Addressing underlying risk factors, such as controlling diabetes and correcting neutropenia, is crucial
• Prognosis: The prognosis of mucormycosis is poor, with mortality rates ranging from 30% to 70%, depending on the site of infection, the underlying health of the patient, and the timeliness of diagnosis and treatment

Key Takeaways

• Mucorales are a group of filamentous fungi that can cause severe, invasive infections, particularly in immunocompromised individuals
• Rhizopus and Mucor are the most common genera causing human infections
• Mucormycosis is a rapidly progressive and often fatal infection
• Laboratory diagnosis involves direct microscopic examination and culture
• Accurate and rapid identification of Mucorales is essential for guiding appropriate treatment
• Aggressive surgical debridement and antifungal therapy are necessary for improving patient outcomes

Key Terms

• Mucorales: An order of fungi characterized by broad, non-septate or sparsely septate hyphae and asexual reproduction via sporangia
• Zygomycetes: An older term for the group of fungi now classified as Mucorales
• Mucormycosis: The disease caused by Mucorales fungi
• Hyphae: The thread-like, branching filaments that form the mycelium of a fungus
• Non-Septate Hyphae: Hyphae that lack cross-walls (septa), forming a continuous, multinucleated cell
• Rhizoids: Root-like structures that anchor the fungus to the substrate, characteristic of Rhizopus
• Sporangia: Sac-like structures containing spores, used for asexual reproduction by Mucorales
• Rhino-Orbito-Cerebral Mucormycosis (ROCM): The most common form of mucormycosis, involving the sinuses, orbit (eye socket), and brain
• Debridement: Surgical removal of infected tissue
• Amphotericin B: A polyene antifungal drug used to treat mucormycosis
• Isavuconazole: A triazole antifungal drug used to treat mucormycosis
• Posaconazole: A triazole antifungal drug used to treat mucormycosis
• Diabetic Ketoacidosis (DKA): A serious complication of diabetes characterized by high blood sugar, ketones in the urine, and metabolic acidosis
• Neutropenia: A condition characterized by a low number of neutrophils (a type of white blood cell) in the blood. Neutropenic patients are at increased risk for invasive fungal infections
• Deferoxamine: An iron-chelating agent used to treat iron overload. Deferoxamine can increase the risk of mucormycosis by providing iron for the fungus to use
• Liposomal Amphotericin B: A formulation of amphotericin B that is less toxic than the conventional formulation
• Apophysomyces: A genus of Mucorales known to cause aggressive infections, particularly in immunocompromised individuals
• Cunninghamella: A genus of Mucorales that can cause pulmonary and disseminated infections, especially in patients with hematologic malignancies