Clinical Overview of Mucormycosis

At a glance

  • Mucormycosis is a rare but severe fungal infection caused by mucormycete molds, which are found throughout the environment.
  • Mucormycosis primarily affects people who are immunocompromised and those with uncontrolled diabetes.
  • Clinical presentation depends on the body site affected.
  • Treatment requires antifungal therapy with amphotericin B, posaconazole, or isavuconazole and often involves aggressive surgery.
Three pane graphic; first image is of a microscope and shows a zoomed in view of fungal spores above it, The second image is a cleaning product. The third image is a patients on IVs in the hospital

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

People are exposed to mucormycete molds every day without getting sick. Mucormycosis is a risk among people with weakened immune systems. Some medical conditions, blood level abnormalities, medical treatments, and health characteristics or behaviors increase risk for infection.

Medical conditions

Blood level abnormalities

  • Persistent neutropenia.
  • Iron overload.

Medical treatments

  • Stem cell or solid organ transplant.
  • Prolonged corticosteroid therapy.

Other patient characteristics

  • Trauma, burns, or surgical wounds.
  • Intravenous drug use.
  • Malnourishment.
  • Premature birth.

Mucormycosis and COVID-19‎

COVID-19-associated mucormycosis emerged during the pandemic. This became a major public health issue in India, which had approximately 71% of global COVID-19-associated mucormycosis.

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.

Mucormycosis outbreaks are rare. However, there are occasional outbreaks in communities from natural disasters. Flooding and damp conditions promote mold growth and increase injuries.

Outbreaks have also occurred in healthcare settings. Sick patients already are much more likely to get mucormycosis. Mold contamination has happened through adhesive bandages, tongue suppressors, water leaks, poor air filtration, dust from nearby construction, and contaminated linens

Image of a laundry room with shelves of folded towels. A cart with linens is in the middle of the room under a vent that is blowing out spores of mold
Mold from air vents can land on linens and cause hospital outbreaks.

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. It 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. It is challenging to diagnose partly because of its clinical resemblance to necrotizing enterocolitis, a far more common disease.

Disseminated mucormycosis but it usually develops from neutropenic patients with a pulmonary infection, but any form of mucormycosis can disseminate. The most common site of spread is the brain, but the spleen, heart, skin, and other organs can also be affected.

Testing

A lab scientist sitting over a microscope and a female lab scientist holding up a specimen
Laboratory diagnosis of mucormycosis is challenging.

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; 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,. 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.