Gilead Anti-Infectives Forum

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UK-AMB-1047  |  January 2024 © 2024 Gilead Sciences, Inc. All rights reserved

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Risk Factors & Diagnosis

The Gilead Anti-Infectives Forum is a promotional website intended for healthcare professionals in the UK and Ireland, and has been designed, built, and funded by Gilead Sciences Ltd.

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! What could
increase IFI risk? Early
diagnosis Known
symptoms Treatment

Fungi can lead to some of the world's most serious infections1-4

Invasive fungal infections can be life-threatening for patients1-4

With the incidence of invasive fungal infections (IFIs) increasing globally in at-risk patients,5,6 identifying the signs, symptoms, and risk factors early could help you treat IFIs appropriately.1-3,7-11

Who is most at risk of an invasive fungal infection?

Patients at risk of developing an IFI include those who have undergone transplantation (stem cell or solid organ), those prescribed targeted treatments for haematological malignancies and those living with advanced HIV.4-6,11-15 Please note that this list is not exhaustive.

What conditions, procedures and medications could increase IFI risk?

Underlying conditions

Uncontrolled diabetes16
Hospitalisation as a result of COVID-1917-19
Nosocomial bacterial infection11
Multiple organ failure20
Major burns21
Haematological malignancies11-14
HIV/AIDS4,15

Uncontrolled diabetes16
Hospitalisation as a result of COVID-1917-19
Nosocomial bacterial infection11
Multiple organ failure20
Major burns21
Haematological malignancies11-14
HIV/AIDS4,15

Invasive and surgical procedures

Major surgery (including intra-abdominal), organ transplantation, life support measures (including mechanical ventilation), total parenteral nutrition or insertion of medical devices (including shunts and catheters).11

Multiple invasive procedures and prolonged stay in ICU can also increase risk.11,22

Concomitant or prior medications

Immunosuppressants11
Targeted therapies for haematological malignancies12-14
Corticosteroids and widespread use of broad-spectrum antibiotics11,23
Immunosuppressants11
Targeted therapies for haematological malignancies12-14
Corticosteroids and widespread use of broad-spectrum antibiotics11,23

Increasing worldwide antifungal resistance may also contribute to the rising incidence of IFIs.11,24,25

Suspect early

A lack of definitive disease confirmation and access to timely fungal diagnostic test results can often lead to delayed antifungal treatment, increasing the risk of worse outcomes and mortality, compared to earlier treatment initiation.7,26

Early diagnosis and prompt treatment of IFIs in high-risk patients is key to ensuring favourable outcomes.6,7,13,26 Even in immunocompetent patients, if invasive pulmonary aspergillosis is not diagnosed and treated promptly, mortality rates can be higher than if IPA is diagnosed and treated promptly.27

In patients with invasive candidiasisa, mortality was high when antifungal therapy was delayed or inadequate and/or when source control was not quickly achieved.7,9,26

a. Invasive candidiasis includes three clinical conditions: candidaemia, deep-seated candidiasis and deep-seated candidiasis with associated candidaemia.59

Know the signs and symptoms

The symptoms of an IFI can often be non-specific, making diagnosis difficult.28-30 Some of the more common clinical manifestations your patient may present with, include:28

Fever
Cough
Dyspnoea
Expectoration
Fever
Cough
Dyspnoea
Expectoration

Early diagnosis is often challenging:30-37

There are a number of factors which make diagnosis of IFI difficult:

  • Low sensitivity and slow time to positivity of cultures30-32,36
  • Variable laboratory facilities33
  • Low index of suspicion in immunocompetent patients34,35,38
  • Expanding number of invasive fungal species30
  • Slow turnaround times to confirm pathogens36
  • Difficulty differentiating between some species37
  • Difficulty determining if a positive culture is due to colonisation or an active infection37
  • In critically ill patients, biopsy procedures carry risks that may outweigh the benefits37,38

Treat promptly

When the diagnosis or fungal pathogen is unknown, treating eligible patients empirically may help to reduce mortality.9,39-41 Timely initiation of antifungal treatment has been shown to improve survival in some IFIs (e.g. candidiasis and mucormycosis)7,26,42,43

UK: AmBisome® (liposomal amphotericin B) is indicated in adults and children aged 1 month to 18 years old for the empirical treatment of presumed fungal infections in febrile neutropenic patients, where the fever has failed to respond to broad spectrum antibiotics and appropriate investigations have failed to define a bacterial or viral cause.44
IRL: AmBisome® is indicated in adults and children aged 1 month to 18 years old for the treatment of fever of unknown origin (FUO) in neutropenic patients. In this context, FUO is defined as persisting fever, unresponsive to at least 96 hours of antibiotic treatment; it is highly indicative for a systemic fungal infection in this patient population. Before initiating AmBisome treatment, common viral, parasitic or mycobacterial infections should also be excluded as far as possible as causes for the observed FUO45

For a full list of indications please refer to the AmBisome Summary of Product Characteristics.

Fungi & invasive fungal infections Antifungal resistance

Abbreviations

  • AIDS, Acquired immunodeficiency Syndrome
  • BCSH, British Committee for Standards in Haematology
  • BHIVA, British HIV Association
  • COVID-19, Coronavirus Disease 2019
  • ECIL, European Conference on Infections in Leukemia
  • ECMM, European Confederation of Medical Mycology
  • ERS, European Respiratory Society
  • HIV, Human immunodeficiency virus
  • ICU, Intensive Care Unit
  • IDSA, Infectious Diseases Society of America
  • ESCMID, European Society for Clinical Microbiology and Infectious Diseases

References

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UK-AMB-0698 | November 2023