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Pharmacy Notes

Introduction to Fungal Infections

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An in-depth presentation covering fungal biology, infection types, epidemiology, clinical features, diagnostic methods, risk factors, and treatment strategies for superficial and systemic mycoses. Candida Infections

  • mycology
  • fungal infections
  • Candida
  • antifungal drugs
  • mycoses

By Dr. Ayesha Fatima

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  1. Slide 1. INTRODUCTION TO FUNGAL INFECTIONS Presented By Dr. Ayesha Fatima Pharm D Assistant Professor Dept Of Pharmacy Practice
  2. Slide 3. FEATURES OF FUNGI Cellular Structure Eukaryotic organisms: Possess a true nucleus enclosed by a nuclear membrane. Contain typical eukaryotic organelles: Mitochondria, Golgi apparatus, Endoplasmic reticulum (with ribosomes), Cytoplasmic membrane: Contains lipids, glycoproteins, and sterols (e.g., ergosterol). Cytoskeleton: Includes microtubules, microfilaments, and intermediate filaments. Cell Wall Composition Rigid cell wall composed of Chitin, Cellulose, Or both These components can be stained with: Gomori methenamine silver (GMS) Periodic acid–Schiff (PAS) Gram stain: Most fungi (except Candida) are poorly gram-positive and not clearly visible. Special Structures: Cryptococcus neoformans: Surrounded by a polysaccharide capsule (important for virulence and diagnosis).
  3. Slide 4. Form Description Molds Multicellular - Grow as branching hyphae (filaments) Hyphae may be :• Septate (divided by cross-walls) • Coenocytic (non-septate, multinucleate) Yeasts Unicellular, oval or spherical- Grow as pasty or mucoid colonies on agar Reproduce by budding (daughter cell buds off parent cell) Morphological Forms : Fungi exist in two major morphological forms: Dimorphism (Dimorphic Fungi): Dimorphic fungi can switch between yeast and mold forms depending on: Temperature Environment (host vs. laboratory) In humans (host): Exist as yeasts (parasitic form). In the environment/lab: Exist as molds (saprophytic form).
  4. Slide 5. Classification of Fungi
  5. Slide 6. • Fungal infections, or mycoses, are diseases caused by fungi. • These can range from superficial (skin, nails, mucosa) to systemic and life-threatening infections, especially in immunocompromised individuals. • They are broadly categorized as: • Primary (systemic) mycoses: Caused by pathogenic fungi that infect healthy or immunocompromised hosts. • Opportunistic mycoses: Caused by normally harmless fungi in immunocompromised individuals. Epidemiology ❖ The incidence of fungal infections is increasing, especially in hospital and ICU settings. ❖ Nosocomial fungal infections account for a large percentage of bloodstream infections (e.g., Candida spp. are 4th most common). ❖ Candida albicans causes 78% of nosocomial fungal infections. ❖ There's a growing shift in invasive fungal infections (IFIs) from Candida spp. to Aspergillus spp., especially in stem cell transplant and hematologic malignancy patients. ❖ Geographic variation plays a role: ❖ Histoplasma capsulatum → Mississippi & Ohio river valleys ❖ Coccidioides spp. → Southwestern USA ❖ Paracoccidioides → Central & South America FUNGAL INFECTIONS
  6. Slide 8. Type Fungal Pathogens Primary/ Systemic Pathogens a. Histoplasma capsulatum, b. Coccidioides immitis, c. Cryptococcus neoformans, d. Blastomyces dermatitidis, e. Paracoccidioides brasiliensis, f. Sporothrix schenckii Opportunistic Pathogens i. Candida albicans, ii. Aspergillus spp., iii. Mucor, Fusarium, iv. Alternaria, Trichosporon, v. Candida glabrata, vi. Cryptococcus neoformans Etiology
  7. Slide 9. Host-Related Risk Factors Procedure/Environment-Related Risk Factors Special Population 1. Immunosuppression: 1. Hematologic malignancies 2. Stem cell/organ transplant 3. HIV/AIDS 4. Autoimmune disease treatments 2. Neutropenia: - ANC ≤ 500/mm³ 3. Use of Broad-Spectrum Antibiotics 4. Prior fungal colonization 5. Disruption of skin/mucosa (e.g., burns, surgery) 6. Altered gut microbiota 7. Malnutrition 1. ICU Admission 2. Central venous catheters (CVCs) 3. Parenteral nutrition 4. Prolonged mechanical ventilation 5. Renal failure and dialysis 6. Nosocomial exposure 7. Geographical exposure (e.g., caves, soil, birds) 1. Cancer Patients – receiving intensive cancer chemotherapy 2. HSCT recipient 3. Critically ill ICU Patients 4. Burn patients 5. Patients on TPN, Steroids, Multiple antibiotics Risk Factors for Fungal Infections
  8. Slide 10. Mode of Entry: • Inhalation of airborne conidia (e.g., Histoplasma , Aspergillus ) • Direct contact via mucosa or broken skin (e.g., Candida , Sporothrix ) Colonization: • Some fungi, like Candida , are part of the normal flora of GI, skin, or mucosa. Barrier Breach & Proliferation • Antibiotic use or malnutrition may disturb flora balance, enabling fungal overgrowth. • Breach in mucocutaneous barriers facilitates invasion. • In immunocompromised hosts, fungi can invade bloodstream and disseminate to organs. • Fungal cells may persist in macrophages due to resistance to lysosomal enzymes. Immune Evasion: • Altered neutrophil function or reduced numbers reduce clearance. • Pathogens like Cryptococcus use capsules to avoid phagocytosis. Pathophysiology
  9. Slide 11. General Clinical Features • Fever unresponsive to antibiotics (classic in neutropenic patients) • Unexplained sepsis or systemic inflammatory response • Organ-specific symptoms, such as: 1. Lungs: Cough, hemoptysis, pleuritic chest pain, dyspnea (e.g., Aspergillosis) 2. CNS: Headache, altered sensorium, seizures (e.g., Cryptococcosis) 3. Skin: Nodules, ulcers, necrotic lesions 4. GI tract: Pain, diarrhea, bleeding (especially in immunosuppressed patients) 5. Eye: Chorioretinitis or endophthalmitis (fungemia) Signs of dissemination: Skin lesions, ocular findings, altered mental status Fungemia Symptoms (e.g., Candida spp.) • Persistent fever despite antibiotic therapy • Signs of sepsis, organ dysfunction, or shock • Central line or catheter-related infection Clinical Presentation
  10. Slide 12. Diagnosis Method Details Limitations Clinical Evaluation History, immune status, signs, and symptoms Non-specific; must guide lab investigations Direct Microscopy KOH mount, India ink (Cryptococcus), Calcofluor white Rapid but low sensitivity Histopathology Tissue biopsy with fungal stains (PAS, GMS) Invasive, sometimes not feasible Culture Blood, tissue, respiratory secretions on Sabouraud’s dextrose agar Slow (days to weeks), some species grow poorly or not at all Serologic tests Detection of antibodies (e.g., Cryptococcus antigen) Limited utility in immunocompromised hosts Technique Target MALDI-TOF MS Fungal protein fingerprint PNA-FISH rRNA in fungal cells PCR-based assays Fungal DNA Galactomannan (GM) Aspergillus antigen 1,3-β-D-glucan assay Cell wall component (broad-spectrum fungi) T2 Magnetic Resonance (T2MR) Candida spp. DNA in blood Cryptococcal antigen (CrAg) Capsule polysaccharide Traditional Diagnostic Methods • Histopathology may not distinguish similar- looking fungi (e.g., Aspergillus vs Zygomycetes ). Also, culture may reflect colonization, not infection, especially with opportunists. Rapid and Advanced Diagnostic Techniques These aim to improve speed and accuracy, especially when early treatment is critical: Matr Des Pep In S
  11. Slide 13. Treatment
  12. Slide 14. SUPERFICIAL CUTANEOUS MYCOSES ► Superficial cutaneous mycoses are fungal infections limited to the skin, hair, and nails. ► They are caused primarily by keratinophilic fungi (dermatophytes) that can invade keratinized tissues but do not penetrate deeper into the body. Epidemiology ► These infections affect 20–25% of the global population, making them one of the most common human infections worldwide. ► They occur in both males and females, across all races and age groups.
  13. Slide 15. Etiology A. Causative Fungi Dermatophytes (most common): o Genera: Trichophyton , Epidermophyton , Microsporum o These fungi digest keratin, allowing them to colonize the skin, nails, and hair. Non - dermatophyte fungi: o Malassezia furfur (especially in pityriasis versicolor) o Yeasts: Candida species (especially in mucocutaneous infections) B. Reservoirs of Infection ∙ Humans (anthropophilic) ∙ Animals (zoophilic) ∙ Soil (geophilic)
  14. Slide 16. Risk Factors ► Warm, moist environments ► Prolonged sweating or water exposure ► Maceration (softening of skin due to moisture) ► Intertriginous areas (skin folds) ► Sharing personal items (combs, towels) ► Crowded living conditions (e.g., dormitories, military barracks)
  15. Slide 17. Pathophysiology ► Dermatophytes adhere to the stratum corneum, penetrate keratin, and begin to grow outward in a ring-shaped (annular) pattern. ► This causes the classic lesion with: ► A central clearing ► A red, scaly, elevated "active" border ► In contrast to conditions like psoriasis or lichen planus, dermatophyte lesions often have this distinct pattern. ► Nail infections (onychomycosis) present as chalky, brittle, discolored nails—usually dull yellow or white.
  16. Slide 18. Clinical Presentation & Diagnosis ► C linical history and physical exam are the first steps. ► Mycotic infections of the skin have a classic appearance that consists of a central clearing surrounded by an advancing red, scaly, elevated border, also referred to as an “active” border. ► Direct KOH microscopy: ► Quick and inexpensive ► Detects fungal hyphae ► Fungal culture: ► Confirms species ► Takes longer and is more costly ► Diagnostic tests are strongly recommended when: ► Systemic (oral) therapy is considered ► The diagnosis is uncertain
  17. Slide 19. Goals of Treatment 1. Eradication of the fungal organism. 2. Clinical cure and nail appearance improvement. Even after successful treatment, nails may remain dystrophic due to preexisting damage—this should be explained to patients to avoid dissatisfaction. General Approach 1. Keep area clean and dry 2. Avoid contact with infectious sources 3. Address predisposing factors (e.g., excessive moisture, poor hygiene) 4. Onychomycosis affects quality of life (pain, cosmetic issues, reduced mobility). 5. Treatment is not always necessary for mild, asymptomatic cases. 6. Untreated cases may lead to cellulitis, reduced mobility, and fungal transmission (e.g., in diabetics or communal settings). 7. Individualized treatment decisions are key—consider disease severity, comorbidities, and patient preferences. 8. Success assessment requires months of follow-up due to slow nail growth (~1 mm/month). 9. Patient adherence and education are crucial for success and preventing recurrence.
  18. Slide 20. N on-Pharmacologic Therapy ► Mechanical/chemical nail avulsion : ► Adjunct to oral therapy. ► Used in total dystrophic onychomycosis with severe thickening or onycholysis. ► Enhances antifungal penetration into nail unit. Pharmacologic Therapy Topical antifungals : o First-line for localized skin infections o Examples: azoles, allylamines, ciclopirox Oral antifungals : o Used for extensive or severe infections, tinea capitis, and onychomycosis o Examples: terbinafine, itraconazole, griseofulvin
  19. Slide 21. A. Topical Therapy ∙ Formulations: Creams, ointments, powders, solutions, lacquers. ∙ Best for: o Superficial infections, limited nail involvement (<50%), no matrix involvement. o Early distal subungual onychomycosis or when oral therapy is contraindicated. ∙ Nail Lacquers : o Ciclopirox 8% (Penlac) – FDA-approved; requires daily use for 1 year, cure rate ~9–32%. o Amorolfine 5% – Higher cure rates (not FDA-approved in US). ∙ Advantages : o Minimal systemic side effects. o Useful in mild or early infections. ∙ Limitations : o Poor penetration if nail plate intact. o Requires prolonged application and good adherence.
  20. Slide 22. B. Systemic Therapy ∙ First-line : o Terbinafine (fungicidal, best for dermatophytes). o Itraconazole (fungistatic, broader spectrum incl. Candida, molds). ∙ Alternative : o Fluconazole (off-label, lower efficacy). ∙ Old drugs (less used due to poor efficacy and safety): Griseofulvin, Ketoconazole.
  21. Slide 23. 1.Terbinafine ∙ Dose: 250 mg/day for 12 weeks (toenails); 6 weeks (fingernails). ∙ Mycologic cure: 77–100%. ∙ Persists in nail up to 36 weeks post-treatment. ∙ Well tolerated, rare hepatotoxicity (check LFTs). ∙ Few drug interactions (inhibits CYP2D6). 2. Itraconazole ∙ Pulse therapy preferred: 200 mg twice daily for 1 week/month × 2–3 months. ∙ Alternative: Daily for 6 weeks (fingernails) or 12 weeks (toenails). ∙ Persists in nails for ~27 weeks. ∙ Avoid in heart failure and liver disease. ∙ Many CYP3A4 drug interactions. 3. Fluconazole ∙ Dose range: 50 mg/day to 300 mg/week for 6–12 months. ∙ Mycologic cure ~48%. ∙ Not FDA-approved but well tolerated, fewer interactions.
  22. Slide 24. Different Types Of Mycotic Infections Of The Skin, Hair, And Nails Infection Site Affected Key Features Causative Organisms Treatment Notes Tinea Pedis (Athlete’s foot) Interdigital spaces, plantar surface, soles Interdigital scaling, fissuring, moccasin-type thickening, vesicles T. rubrum, T. mentagrophytes Topical antifungals (2–4 wks); Oral for severe cases Recurs in up to 70%; often with onychomycosis Tinea Manuum Palms (usually one hand), can involve feet Dry, hyperkeratotic palms; vesicles if nails involved Usually same as tinea pedis Topical/oral antifungals; emollients with lactic acid Often coexists with tinea pedis Tinea Cruris (Jock itch) Groin, inner thighs, buttocks Red, scaling plaques with raised, active border; scrotum often spared T. rubrum Topical antifungals; oral for severe; short-term steroids Examine feet as possible source Tinea Corporis (Ringworm) Glabrous skin – trunk, limbs, face Annular lesion with central clearing and raised edge T. rubrum, T. mentagrophytes Topical; oral if widespread KOH test confirms; steroids may mask typical appearance Tinea Capitis Scalp, hair follicles Hair loss, scaling; mainly in children T. tonsurans, M. canis Oral antifungals (e.g., griseofulvin); antifungal shampoo Treat family carriers to prevent spread Tinea Barbae Beard and mustache areas Follicular pustules, nodules; hair loss T. verrucosum, T. mentagrophytes Oral antifungals; shaving recommended Adult males only Pityriasis Versicolor (Tinea versicolor) Trunk, face,
  23. Slide 26. Condition Topical Treatments Oral Regimen Tinea pedis 1. Butenafine, daily 2. Luliconazole, daily 3. Naftifine, daily Fluconazole 150 mg once/week × 1–4 weeks Tinea corporis 1. Econazole, daily 2. Miconazole, twice daily 3. Terbinafine, daily Terbinafine 250 mg/day × 2 weeks Tinea cruris 1. Clotrimazole, twice daily 2. Luliconazole, daily 3. Naffine cream, daily Itraconazole 200–400 mg/day × 1 week Tinea capitis Topical shampoos only (adjunct): 1. Selenium sulfide 2. Ketoconazole 3. Undecylenic acid Terbinafine 250 mg/day × 4–8 weeks
  24. Slide 27. Onychomycosis 1. Ciclopirox 8% lacquer (48 weeks) 2. Efinaconazole 10% (48 weeks) 3. Tavaborole 5% (48 weeks) Terbinafine 250 mg/day × 6–12 weeksItraconazole 200 mg twice daily (pulse)Fluconazole 50–300 mg/week ≥6 months Pityriasis versicolor 1. Clotrimazole, twice daily 2. Ketoconazole, daily 3. Sulconazole, twice daily Fluconazole or Itraconazole 200 mg daily × 3–7 days
  25. Slide 28. Mucocutaneous Candidiasis ► Mucocutaneous Candidiasis : Persistent or recurring infection with candida species effecting mouth, scalp, skin, nails or other sites. ► Mucocutaneous Candidiasis occurs in 3 forms 1. Oropharyngeal 2. Esophageal 3. Vulvovaginal
  26. Slide 31. Sign and symptoms and Diagnosis
  27. Slide 32. Treatment Goals of Therapy The goal of therapy is complete resolution of symptoms in patients who have symptomatic VVC. General Approach 1. Remove or improve any predisposing factors, if they can identify 2. Avoid use of harsh soaps, perfumes, tight or constrictive clothing, prolonged or frequent hot tub use and douching ( Rinsing or washing inside of vagina ) 3. Keep genital areas clean and dry Non Pharmacological treatment Use of oral lactobacillus, yogurt Pharmacological Treatmen t Effective antimycotic agent should have limited local and systemic side effects, high cure rate and easy administration.
  28. Slide 33. Treatment for uncomplicated VVC
  29. Slide 34. Treatment for complicated VVC 1. Occurs majorly in patients with immunocompromised, uncontrolled DM, pregnancy 2. Treatment is aggressive for 10 to 14 days 3. Antimycotic agents used for 10 to 14 days → Two dose regimen of fluconazole cure 80% of complicated VVC and 2nd dose given after 72 hours of 1st dose 4. Pregnant female should be treated with topical imidazoles for 7 days, oral therapy is contraindicated due to birth defects. Most effective drug is Nystatin Antifungal resistant VVC Individuals resistant to azoles or antimycotic agents → Boric acid 600 mg Intavaginal Capsule OD for 14 days followed by maintenance regimen for 2 weeks Or 5- Flucytosine cream administered intavaginally 1000 mg inserted nightly for 7 days
  30. Slide 35. OROPHARYNGEAL AND ESOPHAGEAL CANDIDIASIS ► These are common and localized infections that occur in patients with HIV infection, DM, Leukemia and other malignancies and also associated with antimicrobial therapy, steroid use, radiation therapy and denture use. ► OPC is referred to as Thrush or candidiasis caused by yeast candida majorly by candida albicans, ► Infection extending into the esophagus called esophageal candidiasis. Etiology 1. Candida albicans 2. Candida glabrata 3. Candida tropicalis 4. Candida dubliniensis
  31. Slide 38. Types Of Oropharyngeal Candidiasis Type Population at Risk Clinical Signs & Appearance Pseudomembranous (Thrush) - Neonates - HIV or cancer patients - Elderly, debilitated - Broad-spectrum antibiotics/steroids - Dry mouth, smokers - White/yellowish "cottage cheese" plaques on buccal mucosa, tongue, gums - Easily scraped off, may leave red/bleeding areas - Bald, depapillated tongue dorsum Erythematous (Atrophic) - HIV patients - Those on antibiotics/steroid inhalers - Painful red mucosa - Few or no white plaques - Flat red patches on palate or tongue - Loss of papillae on tongue - Acute or chronic Hyperplastic (Candidal Leukoplakia) - Smokers - Rare in HIV - Thick white, adherent keratotic plaques on buccal mucosa, tongue borders, lips - Cannot be scraped off easily - May progress to dysplasia or malignancy Angular Cheilitis - HIV patients - Denture wearers - Painful, red cracks at corners of mouth - May be punctate or extend along the skin folds Denture Stomatitis (Chronic Atrophic) - Elderly denture wearers - Poor oral hygiene - Red, flat mucosa under dentures - More common with maxillary dentures Central Papillary Atrophy (Median Rhomboid Glossitis) - Rare (<1%) - More in men (3:1) - Rhomboid red/atrophic or hypertrophic area - Midline dorsal tongue- May not completely resolve
  32. Slide 39. Clinical Presentation and Diagnosis of OPC and EC Feature Oropharyngeal Candidiasis (OPC) Esophageal Candidiasis General - Often diverse in presentation - Common in immunocompromised patients - Often occurs as an extension of OPC - May also occur alone - Affects distal two-thirds of esophagus most commonly Symptoms - Can be asymptomatic - Sore or painful mouth - Burning tongue- Metallic taste - Dysphagia (difficulty swallowing) - Odynophagia (painful swallowing), especially if hypopharynx involved - Dysphagia , odynophagia - Retrosternal chest pain - Rare: epigastric pain - Sometimes asymptomatic Signs - Erythema and white patches on buccal mucosa, tongue, throat, gums - No constitutional signs (e.g., fever) - Fever may occur - White or beige plaques in esophagus - Hyperemic/edematous mucosa - May have ulceration, mucosal friability, lumen narrowing - Rare: Perforation or aorto-esophageal fistula Laboratory Tests - Microscopy (scraping → pseudohyphae, budding yeast) - Culture usually not needed unless resistant case - Upper GI endoscopy is the best test - Helps exclude other causes (viral, aphthous ulcers) - Biopsy to confirm Candida - Culture needed in resistant or non-responding cases
  33. Slide 40. TREATMENT Goals of Treatment : 1. Primary outcome → Elimination of clinical sign and symptoms 2. Prevent complications 3. Minimizing no of future occurrences 4. Minimize toxicities, DDI of systemic antifungal agents General Approach : 1. Management of OPC should be individualized for each patients by taking into consideration of patients immune status, other concurrent mucosal and medical devices, concurrent medication exogenous infections sources. 2. Minimize predisposing factors such as administration of corticosteroids, chemotherapeutic against and antimicrobials.
  34. Slide 41. P harmacologic therapy : 1. Management of OPC should be individualized for each patients by taking into consideration of patients immune status, other concurrent mucosal and medical devices, concurrent medication exogenous infections sources. 2. Minimize predisposing factors such as administration of corticosteroids, chemotherapeutic against and antimicrobials 3. Selection of antifungal agents a. Patients drug adherence b. Adequate saliva for dissolution of solid topic medicine c. Risk of caries from sucrose or dextrose containing preparations d. Potential DDI e. Co existing medical conditions f. Location and severity of infection g. Need for long term therapy h. Resistance
  35. Slide 42. Topical antimycotic therapy : 1. First line therapy for milder forms of infection 2. Topical agents include Nystatin and Clotrimazole 3. Available in different formulations - Oral suspensions, trouches, mucoadhesive tablets, creams and powders 4. Requires frequent applications because of short contact time period with oral mucosa. 5. Clotrimazole troches ⇒ Needs saliva for dissolution, difficult in xerostomia patients, contain dextrose. 6. Nystatin suspension ⇒ Drug of choice in xerostomia patients, Bad taste, cause N/V, Contain high sugar content caution in DM and dentate patients 7. Miconazole mucoadhesive tablet - 50mg ⇒ Taste less, odour less, sugar less tablets used in patients > 16 years of age OD 8. Topical creams → Clotrimazole, Ketoconazole, Miconazole, Nystatin + Steroid Best to treat angular cheilitis ( cracks at mouth corners, inflammation and drying) * 3 days
  36. Slide 43. Systemic antimycotic therapy : 1. Indicated in moderate to severe cases, refractory OPC, immunocompromised patients, EC, and patients who cannot tolerate topic agents. 2. Systemic agents include Fluconazole, Ketoconazole, Itraconazole, Amphotericin B, Voriconazole, Posaconazole, Echinocandins → Caspofungin, micafungin 3. Fluconazole ⇒ Most common, inexpensive, well tolerated , over use may lead to resistance.

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