General Characteristics

Basic features of Candida

• Genus within the Saccharomycetaceae family
• Dimorphic:
  • Yeast
    • Small
    • Oval
    • Unicellular
    • Reproduce by budding
  • Pseudohyphal and hyphal forms
• Gross colony appearance:
  • Round
  • White or cream-colored
• Characteristics:
  • Ferments: 
    • Glucose
    • Maltose
    • Sucrose
  • C. albicans does not ferment lactose.

Clinically relevant species

The most clinically relevant Candida species include:

• C. albicans (most common)
• C. glabrata
• C. parapsilosis
• C. tropicalis
• C. krusei
• C. auris (emerging, multidrug-resistant species)

Pathogenesis

Reservoir

Candida albicans is part of the normal human flora, particularly:

• Oropharynx
• GI tract
• Genitourinary tract
• Skin

Transmission

• Candida is usually transmitted to newborns during childbirth and becomes part of the normal flora.
• Endogenous spread from colonized sites can occur through:
  • Mucosal disruptions (often in oropharynx of GI tract)
  • Indwelling catheters (e.g., central venous catheters, urinary catheters

Host risk factors

Candidiasis is the most common opportunistic fungal infection. 

General risk factors for candidiasis:

• Hot weather
• Restrictive clothing
• Infrequent undergarment or diaper changes
• Antibiotic therapy
• Skin conditions (particularly affecting skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin folds)
• Xerostomia
• Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
• Immunosuppression 
  • HIV/AIDS
  • Hematologic malignancies
  • Individuals who have undergone transplantation
  • Immunosuppressive therapy
  • Diabetes

Additional risk factors for invasive disease:

• ICU hospital stay
• Central venous catheters
• Total parenteral nutrition
• Renal failure requiring dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis
• Abdominal surgery
• GI tract perforation or anastomotic leak

Virulence factors

• Cell-surface adhesins: facilitates adherence to host cells
• Biofilm formation: provides protection from host defenses and antimicrobials
• Extracellular hydrolytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes: facilitate invasion into host tissue
• Hyphae: facilitate tissue invasion

Pathophysiology

• Host defense against Candida infection: 
  • Epithelial barrier
  • T-cell–mediated immunity
  • Macrophages and neutrophils
• Superficial infection:
  • Disruption of normal flora or host immunity → overgrowth of Candida
  • Epithelial desquamation → buildup of keratin and necrotic tissue → pseudomembrane forms on mucosa
  • Underlying edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and ulceration can develop.
• Invasive infection:
  • Disruption of mucosal barrier and immune evasion → tissue penetration 
  • Vascular invasion can occur → dissemination to other host tissues

Diagnosis and Management

Diagnosis

Identification of Candida organisms can be made with:

• Wet mount with 10% KOH of sample scrapings
  • Budding yeast
  • Pseudohyphae or hyphae
• Fungal cultures
• Tissue biopsy

Management

Localized mucocutaneous infections:

• Topical antifungals :
  • Miconazole
  • Nystatin
• Systemic antifungals (fluconazole, itraconazole) can be used for:
  • Extensive disease
  • Esophageal candidiasis

Invasive infection:

• Requires treatment with IV antifungals
• Options include:
  • Fluconazole
  • Voriconazole
  • Caspofungin
  • Amphotericin B

Differential Diagnosis

• Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus: idiopathic, cell-mediated inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin disease. Lichen planus Lichen planus Lichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus is characterized by pruritic, flat-topped, papular, purple skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions commonly found on the flexural surfaces of the extremities. Lacy web-like lesions and painful erosions can occur in the oral and genital regions. Biopsy of the most prominent lesion is used for confirmation of the diagnosis. Topical corticosteroids are the preferred treatment.
• Leukoplakia Leukoplakia Leukoplakia is a potentially malignant lesion affecting the squamous epithelium usually within the oral cavity. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium. Leukoplakia: potentially malignant lesion affecting squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium, usually within the oral cavity. Leukoplakia Leukoplakia Leukoplakia is a potentially malignant lesion affecting the squamous epithelium usually within the oral cavity. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium. Leukoplakia Leukoplakia Leukoplakia is a potentially malignant lesion affecting the squamous epithelium usually within the oral cavity. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium. Leukoplakia presents as a white plaque that cannot be scraped off. Diagnosis is confirmed with biopsy. The lesion can be surgically treated, but close observation is always recommended owing to the risk for malignant transformation.
• Tinea infections Tinea Infections Tinea infections are a group of diseases caused by fungi infecting keratinized tissue (hair, nails, and skin). These infections are termed dermatomycoses and are caused by the dermatophyte fungi. There are approximately 40 dermatophyte fungi that are part of 3 genera, including Trichophyton, Epidermophyton, and Microsporum. These infections can affect any part of the body but occur most often in warm, moist regions like the groin and the feet. Dermatophytes/Tinea Infections: group of diseases caused by dermatophyte fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview infecting keratinized tissue. These infections can affect any part of the body but occur most often in warm, moist region, such as the groin and the feet. The diagnosis is clinical with characteristic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin findings, but it can be confirmed with microscopy of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin scrapings. Treatment depends on the site and magnitude of infection but typically begins with topical antifungals and may progress to oral medications if topical treatment fails.
• Aspergillosis Aspergillosis Aspergillosis is an opportunistic fungal infection caused by Aspergillus species, which are common spore-forming molds found in our environment. As Aspergillus species are opportunistic, they cause disease primarily in patients who are immunocompromised. The organs that are most commonly involved are the lungs and sinuses. Aspergillus/Aspergillosis: opportunistic fungal infection caused by Aspergillus species. Organs that are most commonly involved are the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs and sinuses. Invasive aspergillosis can spread hematogenously and may involve the brain, heart, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin. The diagnosis is made based on imaging, fungal cultures, and serologic or respiratory sample studies. Management depends on the presentation, but it can include antifungal therapy and surgical resection in severe disease.
• Cryptococcosis Cryptococcosis Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. The majority of affected patients are immunocompromised. Patients with AIDS, chronic steroid use, and organ transplant are particularly affected. Cryptococcosis is an AIDS-defining illness and typically associated with CD4 count < 100 cells/μL. Cryptococcus/Cryptococcosis: opportunistic infection caused by the yeast Cryptococcus Cryptococcus Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. Cryptococcus neoformans is typically found in pigeon droppings and acquired by inhaling dust from contaminated soil. The majority of affected patients are immunocompromised. Cryptococcus/Cryptococcosis neoformans or C. gattii. Individuals may develop pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, or cutaneous disease.  Fungal cultures and cryptococcal antigen testing can provide the diagnosis. Management depends on the presentation, but it can include fluconazole and amphotericin B (for meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis).
• Mucormycosis Mucormycosis Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis: angioinvasive fungal infection caused by multiple fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview within the order Mucorales Mucorales Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis. Inhalation of fungal spores can cause rhinocerebral mucormycosis or pulmonary mucormycosis. Direct inoculation can cause cutaneous mucormycosis, and ingestion can result in GI mucormycosis. Symptoms result from fungal hyphae invading the blood vessels, causing thrombosis and, ultimately, necrosis of tissues. Diagnosis is confirmed with biopsy. Mucormycosis Mucormycosis Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis must be treated aggressively with surgical resection and antifungals.