What is invasive candidiasis?

Invasive Candidiasis Definition

Invasive candidiasis is defined as a serious infection caused by Candida species that involves the bloodstream (candidemia) or deep tissue invasion affecting any organ, representing the most common cause of invasive fungal infections in humans. 1, 2

Key Characteristics of Invasive Candidiasis

• Invasive candidiasis encompasses three main clinical entities: candidemia without deep-seated infection, candidemia with deep-seated infection, and deep-seated candidiasis without candidemia 1

• It is primarily a healthcare-associated infection that affects critically ill patients, those undergoing major abdominal surgeries, or individuals with compromised immune systems 1

• Candidemia is the most commonly diagnosed manifestation and ranks as the third or fourth most common cause of healthcare-associated bloodstream infections in the United States 1

• The attributable mortality of invasive candidiasis ranges from 15-47%, with higher rates (up to 100%) in patients with septic shock who do not receive appropriate treatment within 24 hours 1

Causative Organisms

• While Candida albicans has historically been the most common species, non-albicans Candida species now account for approximately 50% of invasive infections 1

• Five species account for over 90% of invasive candidiasis cases: Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei 1

• There is considerable geographic, center-to-center, and even unit-to-unit variability in the prevalence of pathogenic Candida species 1

Clinical Manifestations

• Invasive candidiasis can manifest as:

  • Candidemia (Candida in the bloodstream) 1, 2
  • Deep-seated infections affecting various organs including the liver, spleen, heart, eyes, brain, and bones 1
  • Intra-abdominal candidiasis (IAC), which may occur with or without candidemia 1
  • Chronic disseminated (hepatosplenic) candidiasis 1
  • Endocarditis and infections of implantable cardiac devices 1
  • Central nervous system infections 1

• Signs and symptoms are typically non-specific, making diagnosis challenging 2

Risk Factors

• Major risk factors include:
  • Use of broad-spectrum antibacterial agents 1
  • Presence of central venous catheters 1
  • Receipt of parenteral nutrition 1
  • Renal replacement therapy in ICU patients 1
  • Neutropenia 1
  • Use of implantable prosthetic devices 1
  • Receipt of immunosuppressive agents (including glucocorticosteroids, chemotherapeutic agents, and immunomodulators) 1
  • Major abdominal surgery 1, 2
  • Prolonged ICU stay 2

Diagnostic Challenges

• Blood cultures remain the gold standard but have limited sensitivity (approximately 50%) and slow turnaround times (median 2-3 days) 1

• Deep-seated candidiasis may persist after bloodstream clearance or occur without candidemia, making diagnosis particularly challenging 1

• Non-culture diagnostic methods are increasingly used to enable earlier diagnosis:

  • β-D-glucan detection 1
  • Mannan/anti-mannan antibody assays 1
  • PCR-based techniques 1
  • Magnetic biosensor technology (T2 Biosystems) 1

• Intra-abdominal candidiasis is particularly difficult to diagnose, with only 6.9% of patients having concurrent positive blood cultures 1

Clinical Impact and Outcomes

• The estimated additional cost of each episode of invasive candidiasis in hospitalized adults is approximately $40,000 1

• Early intervention with appropriate antifungal therapy and source control (e.g., catheter removal, drainage of infected material) is associated with better outcomes 1

• Despite advances in healthcare and antifungal development, mortality rates have not substantially improved over recent decades 3

Common Pitfalls and Caveats

• Distinguishing between Candida colonization and infection can be challenging, especially in intra-abdominal samples where mixed infections with bacteria are frequent 1

• Delays in initiating appropriate treatment are associated with increased mortality, leading to empirical antifungal therapy in high-risk patients without documented infection 4

• The sensitivity of blood cultures is limited, potentially missing cases of deep-seated candidiasis without candidemia 1

• Antifungal resistance patterns vary by species and geographic region, necessitating knowledge of local epidemiology when initiating empiric therapy 1

• Overuse of empirical antifungal therapy in critically ill patients without documented invasive candidiasis is a growing concern 4