Pharmaceutical Microbiology and

Parasitology (PHMP211)
Fungi
ž Cell wall = made up of chitin
ž Membrane = made up of ergosterol
ž Microtubule = tubulin

Drugs
ž Amphotericin B – binds to ergosterol on
membranes, induces leakage of fungal cell
ž Griseofulvin – inihibits microtubule synthesis
thus inhibiting fungal mitosis
I. Introduction
A. Current magnitude and
problems of mycoses
ž Fungal infections or mycoses cause a wide
range of diseases in humans.
ž Mycoses range in extent from superficial
infections involving the outer layer of the
stratum corneum of the skin to disseminated
infection involving the brain, heart, lungs,
liver, spleen, and kidneys.
I. Introduction
ž The range of patients at risk for invasive
fungal infections continues to expand beyond
the normal host to encompass patients with
the acquired immunodeficiency
syndrome; those immunosuppressed due
to therapy for cancer and organ
transplantation, and those undergoing
major surgical procedures.
ž Many of the deeply invasive mycoses are
difficult to diagnose early and often
difficult to treat effectively.
B. Concepts of classification
1. According to the site of infection,
fungal infections are designated as
superficial, cutaneous, subcutaneous,
and deep.

a. Superficial mycoses are limited to

the stratum corneum and essentially
elicit no inflammation.
B. Concepts of classification
b. Cutaneous infections involve the
integument and its appendages, including
hair and nails. Infection may involve the
stratum corneum or deeper layers of the
epidermis. Inflammation of the skin is
elicited by the organism or its products.
c. Subcutaneous mycoses include a range of
different infections characterized by infection
of the subcutaneous tissues usually at the
point of traumatic inoculation. An
inflammatory response develops in the
subcutaneous tissue frequently with extension
into the epidermis.
B. Concepts of classification
d. Deep mycoses involve the lungs,
abdominal viscera, bones and or
central nervous system. The most
common portals of entry are the
respiratory tract, gastrointestinal
tract, and blood vessels.
B. Concepts of classification
2. When classified according to the route of
acquisition, a fungal infection may be
designated as exogenous or endogenous
in origin.
a. Exogenous, an infecting organism may be
transmitted by airborne, cutaneous, or
percutaneous routes.
b. An endogenously-acquired fungal infection
may be acquired from colonization or
reactivation of a fungus from a latent
infection.
B. Concepts of classification
3. Fungi may be classified also according
to virulence, as primary pathogens or
as opportunistic pathogens.
a. A primary pathogen may establish
infection in an immunologically normal
host.
b. An opportunistic pathogen requires
some compromise of host defenses in
order for infection to become established.
v Superficial

1. Pityriasis versicolor is a common

superficial mycosis, which is characterized
by hypopigmentation or
hyperpigmentation of skin of the neck,
shoulders, chest, and back. Pityriasis
versicolor is due to Malassezia furfur
which involves only the superficial keratin
layer.
2. Black piedra is a superficial mycosis due to
Piedraia hortae which is manifested by a
small firm black nodule involving the hair
shaft.
3. White piedra due to Trichosporon beigelii is
characterized by a soft, friable, beige nodule
of the distal ends of hair shafts.
4. Tinea nigra most typically presents as a
brown to black silver nitrate-like stain on the
palm of the hand or sole of the foot and and is
caused by Phaeoannellomyces werneckii.
v Cutaneous Mycoses

1. Dermatophytoses are caused by the agents

of the genera Epidermophyton,
Microsporum, and Trichophyton.
2. Dermatomycoses are cutaneous infections
due to other fungi, the most common of which
are Candida spp.

The dermatophytoses are characterized by an

anatomic site-specificity according to genera.
For example, Epidermophyton floccosum
infects only skin and nails, but does not infect
hair shafts and follicles. Whereas, Microsporum
spp. infect hair and skin, but do not involve
nails. Trichophyton spp. may infect hair, skin,
and nails.
Dermatophytoses – differing
causative agents
ž Tinea pedis (athlete's foot) affects the feet
ž Tinea unguium (onychomycosis)affects
the fingernails and toenails
ž Tinea corporis (ring worm) affects the arms,
legs, and trunk
ž Tinea cruris (jock itch) affects the groin area
ž Tinea manuum affects the hands and palm area
(worse than tinea pedis)
ž Tinea capitis affects the scalp
ž Tinea barbae (Barber’s itch) affects facial hair
ž Tinea faciei (face fungus) affects the face
 Athletes’ foot Onychomycosis (Tinea unguium)

Ring worm (Tinea corporis) Tinea cruris (jock itch)

Tinea capitis Tinea barbae

Tinea faciei
 TREATMENT
ž TOPICAL
— Allylamines (Butenafine, Terbinafine)
○ Tinea corporis, cruris OD x 1 week
○ Tinea pedis OD x 2 weeks

— Triazoles (Clotrimazole, Econazole,

Isoconazole, Ketoconazole, Miconazole)
○ Tinea corporis, cruris BID x 2 weeks
○ Tinea pedis BID x 4-6 weeks
 TREATMENT
ž ORAL
— Allylamines (Terbinafine)
○ Tinea corporis 250 mg OD x 2-4 weeks
○ Tinea pedis 250 mg OD x 2-6 weeks
○ Tinea capitis 250 mg OD x 4 weeks
○ Onychomycosis 250 mg OD x 6-12 weeks

— Imidazoles (Itraconazole)
○ Tinea corporis 100 mg OD x 15 days
○ Tinea pedis 100 mg OD x 30 days
○ Onychomycosis 200 mg BID x 3 months
 PATIENT EDUCATION
ž Wash and dry the affected area.
Then, apply a thin layer of the
topical agent once or twice a day for
at least two weeks, or according to
package directions. Extend the
application about an inch beyond
the visible edge to ensure the best
treatment. If you don't see an
improvement after four weeks, see
your doctor.
 PATIENT EDUCATION
ž PREVENTION:
ü Educate yourself and others.
ü Keep clean.
ü Stay cool and dry.
ü Avoid infected animals.
ü Don't share personal items.
v Subcutaneous Mycoses
1. Chromoblastomycosis

ž Subcutaneous mycosis characterized by

verrucoid lesions of the skin (usually of the
lower extremities);
ž Histological examination reveals muriform
cells (with perpendicular septations) or so-
called "copper pennies" that are
characteristic of this infection.
Verrucoid lesion
Muriform cells
ž Chromoblastomycosis is generally
limited to the subcutaneous tissue with
no involvement of bone, tendon, or
muscle.
ž The most common causes of
chromoblastomycosis are Fonsecaea
pedrosoi, Fonsecaea compacta,
Cladosporium carionii, and
Phialophora verrucosa.
ž The disease is also known as
Chromomycosis, Cladosporiosis
(Cladosporium carionii), Fonseca's
disease (Fonsecaea compacta),
Pedroso's disease (Fonsecaea
pedrosoi), Verrucous dermatitis
2. Mycetoma
ž A suppurative and granulomatous
subcutaneous mycosis, which is destructive
of contiguous bone, tendon, and skeletal
muscle.
ž Mycetoma is characterized by the presence
of draining sinus tracts from which small
but grossly visible pigmented grains or
granules are extruded.
ž The causes of mycetoma are more
diverse but can be classified as
eumycotic and actinomycotic
mycetoma.
ž The most common agent of eumycotic
mycetoma is Pseudallescheria boydii
and the most common cause of
actinomycotic mycetoma is Nocardia
brasiliensis.
Fungi causing mycetoma:
Dematiaceous (melanized) fungi
ž Pigmented brown to black.
ž The melanin pigment is deposited in the
cell walls of these organisms.
ž These fungi may produce a range of
infections from superficial to
subcutaneous to deep.
ž Such deep infections due to
dematiaceous fungi are termed
phaeohyphomycosis.
3. Sporotrichosis is the third general
class of subcutaneous mycoses.
ž This infection is due to Sporothrix
schenckii and involves the
subcutaneous tissue at the point of
traumatic inoculation.
ž The infection usually spreads along
cutaneous lymphatic channels of the
extremity involved.
v Deep Mycoses
A. Primary versus opportunistic
mycoses

Deep mycoses are caused by primary

pathogenic and opportunistic fungal
pathogens.
1. The primary pathogenic fungi are able
to establish infection in a normal host
— The primary deep pathogens usually gain
access to the host via the respiratory tract.
— The primary systemic fungal
pathogens include Coccidioides
immitis, Histoplasma capsulatum,
Blastomyces dermatitidis, and
Paracoccidioides brasiliensis.
2. Opportunistic fungi causing deep mycosis
invade via the respiratory tract, alimentary
tract, or intravascular devices.
ž Opportunistic pathogens require a
compromised host in order to establish
infection (e.g., cancer, organ transplantation,
surgery, and AIDS).
ž The opportunistic fungal pathogens include
Cryptococcus neoformans, Candida spp.,
Aspergillus spp., Penicillium marneffei,
the Zygomycetes, Trichosporon beigelii,
and Fusarium spp.
B. Dimorphism in the Pathogenic Fungi
ž Fungal dimorphism is the morphological and
physiological conversion of certain fungi from
one phenotype to another when such fungi
change from one environment to another.
ž Dimorphic fungi include C immitis, H
capsulatum, B dermatitidis, P brasiliensis, P
marneffei, and S schenckii, and certain
opportunistic fungi such as Candida albicans
and Penicillium marneffei.
ž Various environmental host factors control
fungal dimorphism. These factors include amino
acids, temperature, carbohydrates, and trace
elements (e.g. zinc).
Dimorphic fungi

1. S. schenckii, the morphological transformation

is from a hyphal form to a yeast-like form (or
spherule in the case of C immitis) in tissue
2 .the dimorphism of Candida albicans is
somewhat different in that the organism
transforms from a budding yeast-like
structures (blastoconidia) to filamentous
structures known as germ tubes. Other
filamentous structures may later develop as
pseudohyphae and hyphae.
3. Penicillium marneffei is unique in
being the only Penicillium species
pathogenic to humans. It undergoes
dimorphic conversion in vivo to
transversely dividing sausage-shaped
cells.
C. Primary Mycoses
ž Most cases of primary deep mycoses are
asymptomatic or clinically mild infections
occurring in normal patients living or
traveling in endemic areas.
ž Patients exposed to a high inoculum of
organisms or those with altered host
defenses may suffer life-threatening
progression or reactivation of latent foci of
infection.
1. Coccidioidomycosis
ž The arthrococonidia of Coccidioides
immitis are inhaled and convert in the
lung to spherules.
ž Most cases of are clinically occult or mild
infections in patients who inhale infective
arthroconidia.
ž Some patients have progressive
pulmonary infection and also may suffer
dissemination to the brain, bone, and
other sites.
2. Histoplasmosis
ž A primary pulmonary infection resulting from
inhalation of conidia of Histoplasma capsulatum
which convert in vivo into the blastoconidial
(budding yeast) form.
ž Dissemination to the hilar and mediastinal lymph
nodes, spleen, liver, bone marrow, and brain may
be life-threatening in infants and other
immunocompromised patients. Common in
AIDS
ž Histoplasmosis (like tuberculosis) is
characterized by intracellular growth of the
pathogen in macrophages and a granulomatous
reaction in tissue.
ž Histoplasmosis also may be
associated with a chronic inflammatory
process known as fibrosing
mediastinitis, where scar tissue
(formed in response to H. capsulatum)
encroaches on vital structures in the
mediastinum.

ž “mid chest area”

3. Blastomycosis
ž Similar to histoplasmosis, is a primary
pulmonary infection resulting from inhalation
of conidia from the mycelial phase of
Blastomyces dermatitidis which convert in
vivo to the parasitic yeast phase.
ž The organism elicits a granulomatous
reaction often associated with a marked
fibrotic reaction.
D. Opportunistic Mycoses
1. Candidiasis
ž Candidiasis (due to C. albicans and
other Candida spp.) is the most
common opportunistic fungal
infection.
ž Candida albicans is the most
common cause of candidiasis.
Candidiasis may be classified as
superficial or deep.
a. Superficial candidiasis may involve
the epidermal and mucosal surfaces,
including those of the oral cavity,
pharynx, esophagus, intestines, urinary
bladder, and vagina
b. Deep (or visceral) candidiasis.
ž The alimentary tract and intravascular
catheters are the major portals of entry
ž The kidneys, liver, spleen, brain, eyes, heart,
and other tissues are the major organ sites
involved in deep or visceral candidiasis.
ž The principal risk factors predisposing to
deeply invasive candidiasis are protracted
courses of broad spectrum antibiotics,
cytotoxic chemotherapy, corticosteroids,
and vascular catheters.
2. Aspergillosis
ž Invasive aspergillosis most frequently
involves the lungs and paranasal sinuses.
ž The fungus, Aspergillus may disseminate
from the lungs to involve the brain, kidneys,
liver, heart, and bones.
ž The main portal of entry for aspergillosis is
the respiratory tract, however, injuries to the
skin may also introduce the organism into
susceptible hosts.
ž Quantitative and functional defects in
circulating neutrophils are key risk
factors for development of invasive
aspergillosis.

ž Most humans inhale Aspergillus spores

every day but aspergillosis develops
only on immunocompromised
persons.
3. Zygomycosis
ž Zygomycosis due to Rhizopus,
Rhizomucor, Absidia, Mucor species,
or other members of the class of
Zygomycetes, also causes invasive
Sinopulmonary infections.
ž An especially life-threatening form of
zygomycosis (also known as
Mucormycosis), is known as the
rhinocerebral syndrome, which
occurs in diabetics with ketoacidosis.
4. Cryptococcosis
ž Cryptococcosis is most typically an
opportunistic fungal infection that most
frequently causes pneumonia and/or
meningitis.
ž Defective cellular immunity, especially
that associated with the acquired Immune
deficiency syndrome, is the most
common risk factor for Developing
cryptococcosis.
ž It is caused by Cryptococcus
neoformans
5. Phaeohyphomycosis
ž Phaeohyphomycosis is an infection by
brown to black pigmented fungi of the
cutaneous, superficial, and deep
tissues, especially brain.
ž These infections are uncommon, life-
threatening, and occur in various
immunocompromised states.
6. Hyalohyphomycosis
ž Hyalohyphomycosis is an opportunistic
fungal infection caused by any of a
variety of normally saprophytic fungi with
hyaline hyphal elements.