Clinical Overview of Mucormycosis

Cause

Mucormycosis is caused by molds belonging to the order Mucorales, most commonly Rhizopus species. Other causative species include Mucor species, Cunninghamella bertholletiae, Apophysomyces species, and Lichtheimia (formerly Absidia) species.

Risk factors

The following conditions are risk factors for mucormycosis: uncontrolled diabetes; severe COVID-19, malignancy; hematopoietic stem cell transplant or solid organ transplant; persistent neutropenia; prolonged corticosteroid therapy; skin trauma, burns, or surgical wounds; iron overload; intravenous drug use; malnourishment; and being a very premature infant.

How it spreads

Mucormycosis is acquired through inhalation, inoculation, or ingestion of spores from the environment. Most cases are sporadic, and mucormycosis is not contagious.

Very rarely, outbreaks of murocmycosis can occur:

• Healthcare-associated outbreaks have been linked to adhesive bandages, wooden tongue depressors, hospital linens, negative pressure rooms, water leaks, poor air filtration, non-sterile medical devices, and building construction.
•  Community-onset outbreaks have been associated with trauma sustained during natural disasters.

Clinical features

There are five major clinical forms of mucormycosis; of these, rhinocerebral and pulmonary infections are the most common. A classic clinical sign of mucormycosis is the rapid onset of tissue necrosis with or without fever. Necrosis is the result of invasion of blood vessels, subsequent thrombosis, and tissue death.

• Rhinocerebral mucormycosis is the most common form in patients with diabetes and with renal transplants. It also occurs in neutropenic cancer patients and hematopoietic stem cell transplant or solid organ transplant recipients. Symptoms may include unilateral facial swelling, headaches, nasal or sinus congestion or pain, serosanguinous nasal discharge, and fever. As the infection spreads, ptosis, proptosis, loss of extraocular muscle function, and vision disturbance may occur. Necrotic black lesions on the hard palate or nasal turbinate and drainage of black pus from eyes are useful diagnostic signs.
• Pulmonary mucormycosis generally occurs in patients with hematologic malignancy or profound neutropenia. The symptoms are non-specific and include fever, cough, chest pain, and dyspnea. Angioinvasion results in tissue necrosis, which may ultimately lead to cavitation and/or hemoptysis.
• Cutaneous mucormycosis may be primary or secondary. Primary infection is usually caused by direct inoculation of the fungus into disrupted skin, is most often seen in patients with burns or other forms of local skin trauma, and can occur in patients who are not immunosuppressed. Primary infection produces an acute inflammatory response with pus, abscess formation, tissue swelling, and necrosis. The lesions may appear red and indurated and often progress to black eschars. Secondary cutaneous infection is generally seen when the pathogen spreads hematogenously; lesions typically begin as an erythematous, indurated, and painful cellulitis and then progress to an ulcer covered with a black eschar.
• Gastrointestinal mucormycosis is less common than the other clinical forms and is believed to result from ingestion of the organism. It typically occurs in malnourished patients or premature infants. The stomach, colon, and ileum are most affected. Non-specific abdominal pain and distension, nausea, and vomiting are the most common symptoms, and gastrointestinal bleeding can occur. It is the most common form of mucormycosis among neonates and is challenging to diagnose partly because of its clinical resemblance to necrotizing enterocolitis, a far more common disease.
• Disseminated mucormycosis may follow any of the forms of mucormycosis described above but is usually seen in neutropenic patients with a pulmonary infection. The most common site of spread is the brain, but the spleen, heart, skin, and other organs can also be affected.

Testing

A definitive diagnosis of mucormycosis typically requires histopathological evidence or positive culture from a specimen from the site of infection. Specimens from sterile body sites offer stronger evidence of invasive infection compared to colonization. Culture of non-sterile sites (e.g., sputum) may be helpful in patients with infection that is clinically consistent with mucormycosis. Mucormycetes may be difficult to differentiate from other filamentous fungi in tissue; experienced pathological and microbiological assistance is often helpful. No routine serologic tests for mucormycosis are currently available, and blood tests such as beta-D-glucan or Aspergillus galactomannan do not detect mucormycetes. DNA-based techniques for detection are promising but are not yet fully standardized or commercially available. 

Treatment and recovery

Early recognition, diagnosis, and prompt administration of appropriate antifungal treatment are important for improving outcomes for patients with mucormycosis.  Amphotericin B, posaconazole, and isavuconazole are active against most mucormycetes. Lipid formulations of amphotericin B are often used as first-line treatment.  Medications active against Aspergillus such as voriconazole are not active against mucormycetes, and there is some evidence to suggest that pre-exposure to voriconazole may be associated with increased incidence of mucormycosis in some patients. In addition, surgical debridement or resection of infected tissue is often necessary, particularly for rhinocerebral, cutaneous, and gastrointestinal infections. Control of the underlying immunocompromising condition should be attempted when possible.  The efficacy of other treatments such as hyperbaric oxygen therapy is uncertain but have been useful in certain situations.

Complications

Patient prognosis depends on several factors, including the rapidity of diagnosis and treatment, the site of infection, and the patient's underlying conditions and degree of immunosuppression. The overall mortality rate is approximately 50%, although early identification and treatment can lead to better outcomes.