What is candida overgrowth, also known as candidiasis, in individuals with compromised immune systems, diabetes, or those undergoing antibiotic therapy?

What is Candida Overgrowth (Candidiasis)?

Candida overgrowth, or candidiasis, is a fungal infection caused by excessive proliferation of Candida species—most commonly Candida albicans—that normally exist as harmless commensal organisms in the gastrointestinal tract and on mucosal surfaces, but cause disease when host defenses are compromised or normal flora is disrupted. 1

Pathophysiology and Mechanism

Candida species are part of the normal human microbiome, found in the oral cavity of up to two-thirds of healthy individuals. 2 The transition from harmless colonization to pathogenic overgrowth occurs through specific mechanisms:

• Suppression of indigenous intestinal bacteria (typically from broad-spectrum antibiotic use) allows Candida overgrowth in the gastrointestinal tract and enhanced mucosal adhesion. 2
• Once critical colonization levels are reached, translocation across intact small bowel mucosa may occur, particularly in ICU settings where physiological stresses impair mucosal integrity. 2
• Skin colonization provides a source for invasive disease when integrity is breached by intravascular catheters or burns. 2

Spectrum of Disease

Candidiasis encompasses a wide range of clinical presentations, from superficial to life-threatening:

Superficial/Mucocutaneous Forms

• Oropharyngeal candidiasis (OPC) presents in three patterns: erythematous (erythematous patches on palate or tongue), pseudomembranous (creamy white plaques on buccal/oropharyngeal mucosa), and angular cheilitis. 2
• Vulvovaginal candidiasis is characterized by white adherent vaginal discharge with burning and itching, common among healthy women but more severe and recurrent in immunosuppressed patients. 2
• Cutaneous candidiasis in skin folds (including abdominal folds) presents as erythematous, moist patches with satellite pustules at the periphery, maceration, pruritus, and white/creamy exudate in severe cases. 3

Invasive/Deep-Seated Forms

• Deep-seated candidiasis encompasses candidemia with deep-seated infection, deep-seated candidiasis without candidemia, and chronic disseminated (hepatosplenic) candidiasis, occurring in up to 50% of invasive cases. 4
• Organ involvement can include intra-abdominal infections (peritonitis, abscesses, hepatosplenic candidiasis), with mortality rates of 21.7-45% depending on the study. 2, 3

High-Risk Populations

Specific patient groups are at substantially elevated risk:

• HIV/AIDS patients: OPC affects up to 20% of those with advanced HIV disease, often accompanied by esophageal candidiasis. 2
• Diabetes mellitus patients: Impaired cellular immunity predisposes to both mucocutaneous and invasive infections. 2
• Antibiotic therapy recipients: Broad-spectrum antibiotics disrupt normal flora, allowing Candida overgrowth. 2
• Critically ill/ICU patients: Multiple physiological stresses, intravascular catheters, and immunosuppression create ideal conditions. 4
• Hematologic malignancy patients: Especially those with prolonged neutropenia from chemotherapy. 4
• Corticosteroid users: Any drug inhibiting cellular immunity increases risk. 2

Causative Organisms

While Candida albicans remains the most prominent pathogen, the epidemiology is shifting:

• Five species account for >90% of invasive infections: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei. 4
• Non-albicans species emergence: Particularly C. krusei and C. glabrata with intrinsic reduced azole susceptibility, especially in patients with repeated fluconazole exposure. 2
• C. glabrata prevalence in diabetes: This species was isolated in 54.1% of diabetic patients versus 22.6% of controls, with 81.3% showing persistent growth after single-dose fluconazole. 5
• Candida auris: Poses a significant global threat due to multidrug resistance and healthcare transmission. 4

Resistance Patterns

A critical pitfall is assuming all Candida infections respond to azoles. Resistance mechanisms include:

• Acquired fluconazole resistance relates to cumulative exposure (mean 8.7 g in treatment failures), particularly with repeated/prolonged use in profound immunosuppression. 2
• Target enzyme modification: Point mutations in ERG11 gene create altered targets with decreased azole affinity. 6
• Efflux pump upregulation: MDR and CDR genes actively pump fluconazole out of cells. 6
• C. krusei should be considered inherently resistant to fluconazole due to reduced target enzyme sensitivity. 6

Clinical Implications for Practice

The most important distinction is between colonization and infection. Candida can be isolated from multiple body sites without causing disease. 2 In ICU patients, colonization at two or more sites correlates with increased risk of invasive infection, but colonization alone does not mandate treatment. 2

For mucocutaneous infections in immunocompromised patients, the best prophylaxis is addressing the underlying immune deficiency—for HIV patients, this means HAART compliance rather than chronic antifungal prophylaxis. 2 For diabetic patients with vulvovaginal candidiasis, glycemic control is essential, as only one-third respond to single-dose fluconazole when diabetes is poorly controlled. 3, 5