Fungal Infections (Antifungal Drugs)
1.
Introduction
- Fungal infections (mycoses) are diseases caused by fungi.
- They may affect the skin, hair, nails, mucous membranes, lungs,
blood, or internal organs.
- Fungal infections range from mild superficial infections to severe,
life-threatening systemic infections.
- Treatment depends on the type of fungus, site of infection,
severity, and immune status of the patient.
2. Classification of Fungal Infections
A.
Superficial fungal infections
These affect the outer layers of the body.
Examples include:
- Dermatophytosis (ringworm/tinea).
- Tinea corporis.
- Tinea pedis (athlete's foot).
- Tinea cruris (jock itch).
- Tinea capitis.
- Onychomycosis (fungal nail infection).
- Oral candidiasis.
- Vaginal candidiasis.
B.
Systemic fungal infections
These affect internal organs and may become
life-threatening.
Examples include:
- Invasive candidiasis.
- Aspergillosis.
- Cryptococcosis.
- Histoplasmosis.
- Mucormycosis.
3. Goals of Antifungal Therapy
The major goals are:
- Eliminate or control the fungal infection.
- Relieve symptoms.
- Prevent spread of infection.
- Prevent recurrence.
- Reduce complications.
- Minimize drug toxicity.
- Select an antifungal according to the causative organism and site of
infection.
4. Major Classes of Antifungal Drugs
The major antifungal drug classes are:
- Polyenes
- Azoles
- Echinocandins
- Allylamines
- Antimetabolites
- Other topical antifungal agents
5. Polyene Antifungals
Examples
- Amphotericin B.
- Nystatin.
Mechanism
of Action
- Polyenes bind to ergosterol in the fungal cell membrane.
- They form pores in the fungal membrane.
- Cellular contents leak out.
- This leads to fungal cell death.
Simple
memory trick:
“Polyene makes Pores.”
Amphotericin
B
Uses
- Severe systemic fungal infections.
- Invasive candidiasis.
- Cryptococcal infections.
- Severe aspergillosis in selected situations.
- Mucormycosis.
- Other serious life-threatening fungal infections.
Adverse
Effects
- Nephrotoxicity.
- Hypokalemia.
- Hypomagnesemia.
- Fever.
- Chills.
- Infusion-related reactions.
- Anemia.
Important
point
Amphotericin B is highly effective but has significant
toxicity.
Nystatin
Uses
- Oral candidiasis.
- Cutaneous candidiasis.
- Other localized Candida infections.
Important
point
- Mainly used for local fungal infections.
- It is not used for systemic fungal infections.
6. Azole Antifungals
Examples
- Fluconazole.
- Itraconazole.
- Ketoconazole.
- Voriconazole.
- Posaconazole.
- Isavuconazole.
- Clotrimazole.
- Miconazole.
Mechanism
of Action
- Azoles inhibit the fungal enzyme 14-α-demethylase.
- This enzyme is involved in ergosterol synthesis.
- Ergosterol production decreases.
- The fungal cell membrane becomes defective.
Memory
trick:
“AZOLES → Alter ergosterOL.”
Fluconazole
Uses
- Oral candidiasis.
- Vaginal candidiasis.
- Esophageal candidiasis.
- Cryptococcal infections.
- Selected Candida infections.
Advantages
- Good oral absorption.
- Good penetration into cerebrospinal fluid.
- Useful in many Candida infections.
Adverse
Effects
- Hepatotoxicity.
- Gastrointestinal disturbances.
- Drug interactions.
- QT prolongation in susceptible patients.
Itraconazole
Uses
- Dermatophyte infections.
- Onychomycosis.
- Some systemic fungal infections.
- Histoplasmosis and other selected endemic mycoses.
Important
point
- Absorption can vary depending on formulation and gastric conditions.
Adverse
Effects
- Hepatotoxicity.
- Drug interactions.
- Gastrointestinal effects.
- Can worsen heart failure in susceptible patients.
Voriconazole
Uses
- Important treatment option for invasive aspergillosis.
- Used for selected severe fungal infections.
Adverse
Effects
- Visual disturbances.
- Hepatotoxicity.
- Photosensitivity.
- Drug interactions.
Ketoconazole
Uses
- Mainly topical antifungal use in many settings.
Important
point
- Systemic use is limited because of significant toxicity and drug
interactions.
Adverse
Effects
- Hepatotoxicity.
- Endocrine effects.
- Drug interactions.
7. Echinocandins
Examples
- Caspofungin.
- Micafungin.
- Anidulafungin.
Mechanism
of Action
- Inhibit β-(1,3)-D-glucan synthase.
- This prevents synthesis of an important component of the fungal cell
wall.
- The fungal cell wall becomes weak.
Memory
trick:
“ECHINO = destroys the fungal wall.”
Uses
- Invasive candidiasis.
- Severe Candida infections.
- Selected Aspergillus infections.
Adverse
Effects
- Generally well tolerated.
- Fever.
- Gastrointestinal disturbances.
- Liver enzyme abnormalities.
- Infusion-related reactions.
8. Allylamines
Example
- Terbinafine.
Mechanism
of Action
- Inhibits squalene epoxidase.
- This blocks ergosterol synthesis.
- Squalene accumulates inside fungal cells.
- The fungus is damaged or killed.
Memory
trick:
“TERBINAfine blocks SQUALENE.”
Uses
- Dermatophyte infections.
- Tinea infections.
- Onychomycosis.
Adverse
Effects
- Gastrointestinal disturbances.
- Headache.
- Rash.
- Hepatotoxicity.
- Taste disturbances.
9. Antimetabolite Antifungal
Flucytosine
Mechanism
of Action
- Enters fungal cells.
- Is converted into active metabolites.
- Interferes with DNA and RNA synthesis.
Uses
- Often used in combination with amphotericin B.
- Important in treatment of cryptococcal meningitis.
Adverse
Effects
- Bone marrow suppression.
- Hepatotoxicity.
- Gastrointestinal disturbances.
Important
point
- It is commonly used in combination therapy because resistance
can develop when used alone.
10. Other Important Antifungal Drugs
Griseofulvin
Mechanism
- Interferes with fungal mitosis by affecting microtubules.
Uses
- Dermatophyte infections.
- Particularly useful for some infections involving:
- Hair.
- Skin.
- Nails.
Adverse
Effects
- Headache.
- Gastrointestinal disturbances.
- Photosensitivity.
- Hepatotoxicity.
Topical
Antifungal Drugs
Examples include:
- Clotrimazole.
- Miconazole.
- Terbinafine.
- Nystatin.
- Ciclopirox.
Uses
- Mild and localized fungal infections.
- Skin infections.
- Some mucosal infections.
11. Pharmacotherapy According to Type of Infection
A.
Dermatophytosis (Tinea/Ringworm)
Mild
localized infection
- Topical terbinafine.
- Topical clotrimazole.
- Topical miconazole.
Extensive
or severe infection
- Oral terbinafine.
- Oral itraconazole.
- Other systemic treatment depending on the organism and clinical
situation.
B.
Onychomycosis
Common treatment options include:
- Oral terbinafine.
- Itraconazole in appropriate cases.
- Topical therapy for selected mild infections.
Important
point
- Treatment may be prolonged because nails grow slowly.
C.
Oral Candidiasis
Treatment options include:
- Nystatin.
- Clotrimazole.
- Fluconazole for more extensive or severe infection.
D.
Vaginal Candidiasis
Treatment options include:
- Topical azoles.
- Oral fluconazole in appropriate non-pregnant patients.
Important
pregnancy point
- Topical azole therapy is generally preferred during pregnancy, while oral treatment should be selected according to current
medical guidance.
E.
Invasive Candidiasis
Treatment may include:
- Echinocandins as important initial therapy in
many critically ill or invasive cases.
- Fluconazole in selected susceptible and clinically stable patients.
- Treatment should be guided by species identification and antifungal
susceptibility when available.
F.
Aspergillosis
Important treatment options may include:
- Voriconazole.
- Isavuconazole.
- Other antifungal therapy depending on the clinical situation.
Severe cases require specialist management.
G.
Cryptococcal Meningitis
A commonly used treatment approach includes:
- Amphotericin B + Flucytosine for initial
treatment.
This may be followed by:
- Fluconazole for consolidation and
maintenance, depending on the patient and current guidelines.
H.
Mucormycosis
Management usually requires:
- Urgent antifungal treatment.
- Liposomal amphotericin B is an important therapy.
- Surgical removal of infected tissue may be necessary.
- Control of underlying conditions, such as uncontrolled diabetes, is
essential.
12. Important Adverse Effects of Antifungal Drugs
Amphotericin
B
- Nephrotoxicity
- Infusion reactions.
- Hypokalemia.
- Hypomagnesemia.
- Anemia.
Azoles
- Hepatotoxicity
- Drug interactions.
- Gastrointestinal disturbances.
- QT-related cardiac effects for some agents.
Echinocandins
- Liver enzyme abnormalities.
- Fever.
- Infusion-related reactions.
Terbinafine
- Hepatotoxicity.
- Taste disturbances.
- Gastrointestinal effects.
Flucytosine
- Bone marrow suppression.
- Hepatotoxicity.
13. Important Drug Interactions
- Azole antifungals can cause significant drug interactions
because they affect hepatic drug-metabolizing enzymes.
- Before prescribing an azole, concurrent medications should be
carefully reviewed.
- Some azoles can affect drugs used for:
- Anticoagulation.
- Diabetes.
- Epilepsy.
- Transplantation.
- Cardiovascular diseases.
14. Principles of Rational Antifungal Therapy
- Identify the likely fungal organism whenever possible.
- Determine whether the infection is superficial or systemic.
- Select the correct drug according to the infection site.
- Consider the patient's immune status.
- Consider renal and hepatic function.
- Check for drug interactions.
- Use culture and susceptibility testing for serious infections when
available.
- Continue treatment for the appropriate duration.
- Monitor for toxicity.
15. Simple Classification with MOA
POLYENES → Bind ergosterol → Form pores → Cell death
AZOLES → Inhibit 14-α-demethylase → ↓ Ergosterol synthesis
ECHINOCANDINS → Inhibit β-(1,3)-D-glucan synthesis → Weak
cell wall
ALLYLAMINES → Inhibit squalene epoxidase → ↓ Ergosterol
FLUCYTOSINE → Inhibits DNA/RNA synthesis
GRISEOFULVIN → Inhibits fungal mitosis
16. Non-Pharmacological Management
- Maintain good personal hygiene.
- Keep affected areas clean and dry.
- Avoid sharing towels, clothing, and personal items.
- Keep feet dry to prevent tinea pedis.
- Control diabetes and other underlying conditions.
- Avoid unnecessary use of antibiotics.
- Use proper infection-control practices in hospitals.
- Maintain good immune health.