Complications of invasive fungal infections (IFIs)?

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3D image of Candida

INVASIVE FUNGAL DISEASE CAN LEAD TO SOME OF THE WORLD'S MOST SERIOUS INFECTIONS1-4

Infections caused by invasive fungal pathogens can be life-threatening and, for some patients, can cause additional complications.1-3,5-7 What are the serious health implications of invasive fungal infections (IFIs) for your patients?

Two surgeons wearing surgical masks during procedure

IFIs CAN BE LIFE-THREATENING FOR PATIENTS1-4

In some patients, fungal disease can spread to the lungs or central nervous system (CNS), potentially reducing their chance of survival.1-3,5,7 With the incidence of IFIs increasing globally in at-risk patients,8 identifying the signs, symptoms, and risk factors early could help you stay one step ahead.1-3,5-7

WHAT ARE THE LIFE-THREATENING
COMPLICATIONS OF IFIs?

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Fungal sepsis

A key challenge in the intensive care unit (ICU), with increasing incidence and high mortality rates.1,2,5
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CNS infections

Over the past 20 years, fungal infections of the CNS, such as meningitis, meningoencephalitis and neurocandidiasis, have increased.3
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Fungal pneumonia

Pathogens such as Aspergillus or Mucorales can cause pulmonary infections in at-risk patients.9,10
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Photo of doctor in protective overalls caring for patient wearing oxygen mask

WHY IS FUNGAL SEPSIS A GROWING CONCERN IN THE ICU?1,2

Septic shock is a major cause of death in ICUs, with hospital mortality rates of up to 50%.2,5 Whilst all forms of sepsis are life-threatening, fungal sepsis is associated with higher mortality rates than bacterial or viral sepsis, and its incidence is increasing.1,2

Around 5% of all severe sepsis cases are caused by fungi, with Candida albicans and other Candida species the most commonly found.11-14

One of the most frequent sources of septic shock due to candidemia is central venous catheters (CVCs). If the CVC is confirmed as the source of the infection, it is essential to remove and replace the catheter. Patients who do not have their CVC removed have a significantly higher risk of mortality compared with those that do (p=0.006).12

SUSPECT EARLY AND TAKE PROMPT ACTION TO CONTROL FUNGAL SEPSIS IN YOUR ICU

The symptoms of an IFI can be non-specific, leading to difficulty when diagnosing; however, three key steps can help you effectively manage the infection:15

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Know the signs in your at-risk patients and suspect early

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Adequately control the source of the fungal infection16

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Intervene promptly with an appropriate antifungal therapy5,12

Close up of doctor looking at brain scans

HOW MUCH OF A THREAT DO FUNGAL INFECTIONS OF THE CNS POSE TO AT-RISK PATIENTS?3

There are over 300 species of fungal pathogens that may cause disease in humans, and 10-15% of these could impact the CNS.3,7,17

There are various forms of CNS lesions that can occur as a manifestation of fungal infection. Some species, such as Candida, Cryptococcus, and Coccidioides enter the capillaries and subarachnoid spaces, causing meningitis and subpial ischaemic lesions. Candida also enters the blood vessels, resulting in local necrotic lesions, whilst Aspergillus and Mucoromycetes penetrate larger blood vessels, causing infarcts.3,18 Cerebro-rhino-orbital mucormycosis, caused by Mucorales, initially proliferates in the sinuses. It can then spread to the palate, orbit, and brain.18

Some of the most common presentations of CNS infection include meningitis, meningoencephalitis, and brain abscess.3

Photo of doctor sitting on hospital stairs reading chart

WHAT IS FUNGAL MENINGITIS AND WHY SHOULD YOU BE AWARE?

Meningitis is one of the most serious infectious diseases seen across the globe and is associated with high mortality rates and life-altering neurological complications.7 Fungal meningitis often presents with non-specific symptoms, making it difficult to diagnose as it appears similar to other conditions, such as tubercular meningitis.3,19 Cryptococcal meningitis commonly features subacute headache and confusion. Intracranial pressure is often elevated, and may cause cranial nerve palsies or seizures.19

FUNGAL MENINGITIS IS ASSOCIATED WITH HIGH DISEASE BURDEN AND MORTALITY6,7

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Fungi are responsible for up to 6% of meningitis cases7

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Causative species include Cryptococcus, Histoplasma, Blastomyces, Coccidioides, and Candida3

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Immunosuppression, HIV/AIDS, prolonged corticosteroid treatment, organ transplantation, and haematological malignancy are some of the common risk factors3

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WHY IS EARLY SUSPICION OF CRYPTOCOCCAL MENINGITIS IN PATIENTS WITH HIV OR AIDS IMPORTANT?

Cryptococcal meningitis has an extremely high mortality rate, particularly in those with HIV/AIDS, causing over 181,000 deaths globally each year (75% of which occur in sub-Saharan Africa).3

If not suspected early, cryptococcal meningitis can have negative and long-term effects for patients.6

Survivors of cryptococcal meningitis may experience neurological and sensory impairment, causing disability and severe detriment to their quality of life.6 Conditions reported include vertigo, visual loss, hearing impairment, residual headache, and motor deficit.6

TO HELP IDENTIFY PATIENTS WITH SUSPECTED
CRYPTOCOCCAL MENINGITIS, IT IS ESSENTIAL TO KNOW
THE SIGNS

Common signs of cryptococcal meningitis include:3

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Head and neck pain

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Altered mental state

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Convulsions

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Strokes

FUNGAL MENINGOENCEPHALITIS: WHAT CAUSES IT, WHO IS MOST AT RISK AND WHY SHOULD YOU SUSPECT IT EARLY?

Fungal meningoencephalitis is an infection associated with high mortality:20

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Mortality rates can be as high as 90%3

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Causative species include Cryptococcus, Coccidioides, and Candida3

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Disseminated disease, HIV/AIDS, neutropenia, extensive wounds (such as burns), and diabetes are among the risk factors for fungal meningoencephalitis3

Photo of Cryptococcus in a Petri dish under microscope

The most prevalent fungal CNS infection worldwide is cryptococcal meningoencephalitis (mostly caused by Cryptococcus neoformans), affecting approximately 1 million people every year.3

Although primarily associated with advanced HIV/AIDS, it also occurs in solid organ transplant recipients, patients with malignancies and other immunosuppressive conditions, and occasionally in immunocompetent hosts.17

Early detection and prompt initiation of appropriate antifungal therapy remain crucial to reduce mortality. Clinical symptoms to look out for include headache, seizures, cranial nerve abnormalities and altered mental state, which often progress to coma and death.17

Two doctors in an office looking at brain scans on a computer

WHAT CAUSES NEUROCANDIDIASIS AND WHY IS IT IMPORTANT TO SUSPECT EARLY?

Meningoencephalitis is the most common clinical presentation of neurocandidiasis. Mortality resulting from invasive candidiasis is estimated to range from 10-70%; however, in the case of CNS infection, this can be as high as 90%.3

In most cases, CNS involvement is observed in patients who have undergone neurological surgery or developed disseminated disease. It is estimated that up to 6% of patients with disseminated candidiasis have unrecognised neurological infection.3

Photo of Candida particles under microscope

The frequency of Candida albicans has decreased, whilst the prevalence of non-albicans species has increased gradually. Now, 77% of Candida CNS infections in patients with underlying malignant diseases or those who have undergone haematopoietic stem-cell transplantation (HSCT) are caused by non-albicans species, such as C. parapsilosis, C. krusei, C. glabrata, and C. tropicalis.3

Photo of a doctor caring for a woman with respirator in hospital bed

Suspect early to help improve outcomes.3,17,21

When managing life-threatening fungal CNS infections, early diagnosis and prompt treatment are essential to prevent mortality. Identifying at-risk patients and rapid recognition of clinical symptoms may help improve outcomes.3,17,21

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FUNGAL PNEUMONIA: WHAT CAUSES IT AND WHO IS MOST AT RISK?

Due to its high incidence and mortality rates, fungal pneumonia is one of the most severe infections seen in immunocompromised patients.22 It is most commonly seen in neutropenic patients, such as those with haematological malignancies or bone marrow transplant recipients. In these high-risk groups, the incidence can be as high as 56%.23

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Fungal pneumonia accounts for 30% of all deaths among bone marrow transplant recipients22

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Causative species include Aspergillus, Mucorales, Fusarium , Cryptococcus and Candida22

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Risk factors include: widespread use of antibiotics, corticosteroid therapy, solid organ transplantation, haematological malignancy, COVID-19 and influenza, diabetes and mechanical ventilation10,22-24

HOW DOES INVASIVE PULMONARY ASPERGILLOSIS DIFFER FROM BACTERIAL PULMONARY INFECTIONS?

Aspergillus species are the most common opportunistic moulds to cause pulmonary infections, and the number of cases has increased progressively.10,22 The most frequently seen symptoms are cough, fever, and chest pain; however, if dissemination has occurred, other symptoms may manifest.10,23

Patients most at risk of developing invasive pulmonary aspergillosis (IPA) include:10,23

  • those who have undergone HSCT
  • solid organ transplant recipients
  • those with prolonged neutropenia
  • those with prior or concurrent cytomegalovirus infection
  • patients treated with corticosteroids

However, there are increasing reports of the emergence of IPA in patients in the ICU, many of whom are non-neutropenic and not immunocompromised.10,23 Post-viral cases of IPA, including in patients with influenza and COVID-19, have also been reported.24

In influenza patients, coinfection with IPA is associated with a significantly higher mortality rate than other pathogens (66.7% vs. 23.7%, p=0.001).*25

HOW COMMON IS PULMONARY MUCORMYCOSIS AND HOW CAN YOU DIFFERENTIATE IT FROM IPA?

Pulmonary mucormycosis (PM) is an uncommon, but life-threatening, opportunistic fungal infection.9,26 Up to 24% of mucormycosis cases may include pulmonary infection, and the condition is associated with a high mortality rate of 40-76% due to rapid disease progression and prominent angioinvasion.9

Due to the similarities in symptom profile, distinguishing between IPA and PM can be difficult. However, concurrent sinus infection or previous voriconazole therapy may help indicate PM, along with increased numbers of lesions (>10) in CT scans and the presence of pleural effusion.26

Photo of two surgeons wearing masks and face shields

Treat promptly to prevent mortality.10,23,26

Fungal pneumonia often progresses rapidly, so empirical treatment in eligible patients is necessary before histological identification and culture to help improve clinical outcomes. Delays in treatment are associated with a high mortality rate, therefore early suspicion and identification of at-risk patients is essential.25,26

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Footnotes

*Yee-Huang K et al. 2017. Retrospective review of 124 adult patients with severe influenza in a tertiary medical centre in southern Taiwan from January 2015 to March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. ICU mortality in the Aspergillus group (66.7%) was significantly higher than in groups with other co-infections (23.7%, p=0.001), or the control group with no co-infections (15.4%, p<0.001), with significant odds ratios after adjusting for important variables.25

References

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  19. Sloan D and Parris V. Clin Epidemiol. 2014;6:169–182.
  20. Shi M and Mody CH. Front Immunol. 2016;7.
  21. Tjia TL et al. J Neurol Neurosurg Psych. 1985;48:853-858.
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Date of preparation: April 2022. Job code: IHQ-AMB-0424.