What is deep-seated candida infection, also known as systemic or invasive candidiasis, in individuals with compromised immune systems, such as those with Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), undergoing chemotherapy, or taking immunosuppressive medications?

Deep-Seated Candida Infection

Deep-seated candida infection, also known as invasive or disseminated candidiasis, is a serious fungal infection where Candida species invade the bloodstream or penetrate deep into tissues and organs beyond superficial mucosal surfaces, representing the most common invasive fungal infection in humans and carrying mortality rates of approximately 30%. 1, 2, 3

Definition and Clinical Entities

Deep-seated candidiasis encompasses three distinct clinical presentations 2:

• Candidemia with deep-seated infection: Bloodstream infection that has spread to involve one or more organs 2
• Deep-seated candidiasis without candidemia: Organ involvement without detectable bloodstream infection, which occurs in up to 50% of cases 2, 4
• Chronic disseminated (hepatosplenic) candidiasis: A specific syndrome primarily affecting patients with hematological malignancies, typically manifesting after neutrophil recovery following chemotherapy 1

The term "deep-seated" specifically distinguishes invasive tissue and organ involvement from superficial mucosal infections like oral thrush or esophageal candidiasis 1, 2.

Affected Organ Systems

Deep-seated candidiasis can involve virtually any organ system 5:

• Intra-abdominal infections: Including peritonitis, abscesses, and hepatosplenic candidiasis 1
• Cardiovascular: Endocarditis, suppurative phlebitis, and infected vascular grafts 1, 5
• Central nervous system: Meningitis, brain abscesses 1, 5
• Genitourinary: Kidney infections, bladder wall involvement 6
• Musculoskeletal: Osteomyelitis, septic arthritis 6, 5
• Ocular: Endophthalmitis 5
• Pulmonary: Pneumonia, pleural space infections 6

High-Risk Populations

Deep-seated candidiasis primarily affects severely immunocompromised and critically ill patients 1:

• Hematologic malignancy patients: Especially those with prolonged neutropenia from chemotherapy 1
• Hematopoietic stem cell transplant recipients: Particularly those with graft-versus-host disease 1
• ICU patients: Those with multiple risk factors including central venous catheters, broad-spectrum antibiotics, parenteral nutrition, and renal replacement therapy 2, 3
• Post-surgical patients: Especially following major abdominal surgery 1
• HIV/AIDS patients: Those with advanced immunosuppression (CD4 <50 cells/μL) 7

Causative Organisms

Five Candida species account for over 90% of invasive infections 1, 2:

• Candida albicans: Historically most common, now represents approximately 50% of cases 2, 4
• Candida glabrata: Increasing prevalence, often fluconazole-resistant 7, 4
• Candida tropicalis: Common in hematologic malignancies 6, 4
• Candida parapsilosis: Associated with catheter-related infections 6, 4
• Candida krusei: Intrinsically fluconazole-resistant 7, 4

The emergence of Candida auris poses a significant global threat due to multidrug resistance and healthcare transmission 1.

Diagnostic Challenges

Blood cultures remain the gold standard but are positive in only 21-71% of autopsy-proven invasive candidiasis cases, with median turnaround times of 2-3 days. 1, 2, 4

Non-Culture Diagnostic Methods

• β-D-glucan detection: Combined with procalcitonin shows 98% sensitivity and 95% negative predictive value for excluding invasive candidiasis 4
• Mannan antigen and anti-mannan antibodies: Combined testing shows 83% sensitivity and 86% specificity, with results often positive 6-7 days before blood cultures 1
• T2Candida assay: Rapid molecular detection directly from blood 2, 4

Imaging for Hepatosplenic Candidiasis

MRI demonstrates higher sensitivity than CT or ultrasound for detecting liver and spleen lesions, though serological markers (mannan/anti-mannan) may be positive 16 days before radiological detection 1.

Critical Pitfalls

Distinguishing colonization from infection is particularly challenging in intra-abdominal samples where up to 80% of peritonitis patients are colonized with Candida species, and only 6.9% of intra-abdominal candidiasis patients have concomitant candidemia. 1

Key diagnostic considerations 1, 2:

• Positive cultures from urine, respiratory samples, or mucosal surfaces do not necessarily indicate invasive disease 1, 8
• Species identification is essential as virulence and antifungal susceptibility vary significantly 1, 8
• Delays in initiating appropriate antifungal therapy are associated with increased mortality 2
• Antifungal resistance patterns vary by geographic region and institution 2

Clinical Impact

• Mortality: Approximately 30% attributable mortality for candidemia and disseminated infections 3
• Economic burden: Each episode costs approximately $40,000 in additional healthcare expenses 2
• Morbidity: High rates of complications including organ dysfunction and prolonged hospitalization 1, 9

Treatment Principles

Echinocandins (caspofungin, micafungin, anidulafungin) are preferred first-line therapy for critically ill patients and those with suspected azole-resistant species. 1, 7

For severe deep-seated infections (abdominal, CNS, endocarditis), antifungal combination therapy may be beneficial, though evidence is limited 1.

Chronic disseminated candidiasis requires prolonged therapy (minimum 8 weeks) with lipid formulations of amphotericin B or sequential therapy (liposomal amphotericin B followed by fluconazole), and corticosteroids may be considered as it represents an immune reconstitution syndrome. 1