FUNGAL INFECTIONS

Final Year Pharm-D

 Fungal infections
• Fungal infections range from superficial skin infections to life-
threatening systemic infections

• Systemic fungal infections are serious that occur when fungi gain
entrance into the interior of the body

• Fungus  colorless plant that lacks chlorophyll

• Yeast like / mold like  human infections

• Infection  fungal infections  mycotic infections

• Two types
– Superficial mycotic infections
– Deep (systemic) mycotic infections
• Superficial mycotic infections occur on the surface of, or just below,
the skin or nails.
• Superficial infections include tinea pedis (athlete’s foot), tinea cruris
(jock itch), tinea corporis (ringworm), onychomycosis (nail fungus)
• Yeast infections, caused by Candida albicans.
• C. albicans affect women in the vulvovaginal area and can be difficult
to control
• Women who are at increased risk for vulvovaginal yeast infections are
those who have diabetes, are pregnant, or are taking oral
contraceptives, antibiotics, or corticosteroids
• Deep mycotic infections develop inside the body, such as in the lungs
• Treatment for deep mycotic infections is often difficult and prolonged
• Fungicidal  able to destroy fungi
• Fungistatic  able to slow or retard the multiplication of fungi
• Some drugs have an effect on the cell membrane of the fungus, resulting in a
fungicidal or fungistatic effect
– Amphotericin B, miconazole, nystatin , and ketoconazole (Nizoral)
• The fungicidal or fungistatic effect of these drugs appears to be related to their
concentration in body tissues.
• Fluconazole has fungistatic activity that appears to result from the depletion of
sterols (a group of substances related to fats) in the fungus cells.
• Griseofulvin exerts its effect by being deposited in keratin precursor cells, which are
then gradually lost (due to the constant shedding of top skin cells), and replaced by
new, non-infected cells
• The mode of action of flucytosine is not clearly understood
• Clotrimazole binds with phospholipids in the fungal cell membrane, increasing
permeability of the cell and resulting in loss of intracellular components.
 Common fungal infections of skin
Tinea corporis (ringworm)
• Causes and epidemiology
• Fungal infection of the major skin surfaces, excluding the feet, face, hands, groin
and scalp
• Often transmitted by animals (pets or livestock) and can also be picked up from the
soil.
• Children are particularly susceptible and can easily pass it on to other children.
• Adults can also become infected. Farmers and people who work with furry animals
are at increased risk.
Signs and symptoms
• There are itchy pink or red scaly patches
with a well-defined inflamed border.
• Lesions are often paler at the centre,
becoming progressively inflamed towards
the outer edge.
• Lesions often occur singly, but can be
multiple and sometimes overlap to form
a large continuous patch
Differential diagnosis
• Discoid eczema – lesions of similar shape
to ringworm, but larger and mainly
occurring on the arms, legs, hands and
feet.
Treatment  clotrimazole, econazole,
ketoconazole, miconazole and
sulconazole
(topical cream/gel/ointment/lotion)
Tinea cruris (dhobie itch, jock itch)
Causes and epidemiology
Fungal infection caused by dermatophytes of the
groin, occurring almost exclusively in
young men.
Signs and symptoms
• There is a brownish-red itchy rash, with a well-
defined border, in the groin.
• Infection often spreads to involve the lower
abdomen, scrotum and buttocks.
Differential diagnosis
• Contact dermatitis, possibly caused by detergents
used for washing underwear,
may be confused with tinea cruris.
• It is important to diagnose accurately, as
management of the conditions is different.
• The condition may also be confused with erythrasma
(see above).
Treatment
Treatment clotrimazole, econazole, ketoconazole,
miconazole and sulconazole
(topical cream/gel/ointment/lotion).
Pityriasis versicolor / Tinea versicolor
Epidemiology
• It is caused by a type of yeast called Malassezia. The
organism is more common in hot, sunny subtropical areas.
Signs and symptoms
• Macular (flat) patches of altered pigmentation occurring
mainly on the trunk and upper legs and arms. In white-
skinned people patches are brownish and look as if
suntanned, whereas on darker-skinned or heavily tanned
people patches are pale or white. The affected area has
an overall dappled appearance. There is a superficial scale
that can be removed by scraping with a fingernail.
Differential diagnosis
The condition is most likely to be confused with vitiligo.
Treatment imidazole cream applied daily for 3 weeks
ketoconazole 2% shampoo (Apply undiluted and wash off
after 5 minutes). Repeat daily for 1 week, then weekly for
several weeks to prevent reinfection.
selenium sulphide shampoo (wash off after 4–5 hours)
Use weekly for 8 weeks

.
 Systemic fungal infections
• Systemic mycoses  histoplasmosis, coccidioidomycosis, cryptococcosis,
blastomycosis, paracoccidioidomycosis, and sporotrichosis, are caused
by primary or “pathogenic” fungi that can cause disease in both healthy and
immunocompromised individuals

• Mycoses caused by opportunistic fungi such as Candida albicans, Aspergillus spp.,

Trichosporon, Torulopsis (Candida) glabrata, Fusarium, Alternaria, and Mucor are
generally found only in the immunocompromised host
 Specific mycoses
• Histoplasmosis  caused by inhalation of dust-borne microconidia of the dimorphic
fungus Histoplasma capsulatum
• Exposure to low inoculum  mild or symptomatic pulmonary histoplasmosis
• The course of disease is generally benign, and symptoms usually weaken within a
few weeks of onset
• Exposure to a higher inoculum during a primary infection or reinfection may
experience an acute, self-limited illness with flu-like pulmonary symptoms,
including fever, chills, headache, myalgia, and nonproductive cough
• Chronic pulmonary histoplasmosis  opportunistic infection imposed on a
preexisting structural abnormality such as lesions resulting from emphysema.
• Patients demonstrate chronic pulmonary symptoms and apical lung lesions that
progress with inflammation, calcified granulomas, and fibrosis.
• Progression of disease over a period of years (25% to 30% of patients)  cavitation,
bronchopleural fistulas, extension to the other lung, pulmonary insufficiency, and
often death.
• Acute (infantile) disseminated histoplasmosis  infants and young children and
(rarely) in adults with Hodgkin’s disease or other lympho- proliferative disorders 
characterized by fever; anemia; leukopenia or thrombocytopenia; enlargement of
the liver, spleen, and visceral lymph nodes; and GI symptoms nausea, vomiting, and
diarrhea. Untreated disease is uniformly fatal in 1 to 2 months

• In adults  disseminated histoplasmosis demonstrate a mild, chronic form of the

disease. Untreated patients are often ill for 10 to 20 years, with long asymptomatic
periods interrupted by relapses characterized by weight loss, weakness, and fatigue
• Blastomycosis  fungal infection caused by Blastomyces dermatitidis
• Pulmonary disease probably occurs by inhalation conidia, which convert
to the yeast forms in the lungs
• It may be acute or chronic and can mimic infection with tuberculosis, pyogenic bacteria,
other fungi, or malignancy
• Blastomycosis can disseminate to virtually every other body organ, including skin, bones, and
joints, or the genitourinary tract, without any evidence of pulmonary disease
• Clinical presentation
• Acute pulmonary blastomycosis  asymptomatic or self-limited disease characterized by
fever, shaking chills, and a productive, purulent cough, with or without hemoptysis in
immunocompetent individuals
• Sporadic pulmonary blastomycosis  more chronic or subacute disease, with low-grade
fever, night sweats, weight loss, and a productive cough resembling that of tuberculosis
rather than bacterial pneumonia
• Chronic pulmonary blastomycosis  fever, malaise, weight loss, night sweats, and cough
• Diagnosis  The simplest and most successful method  direct microscopic visualization of
the large, multinucleated yeast with single, broad-based buds in sputum or other
respiratory specimens, following digestion of cells and debris with 10% potassium hydroxide.
• Histopathologic examination of tissue biopsies and culture of secretions should be used to
identify B. dermatitidis.