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Mycology
Rose Lily V. Bulosan-Valerio, MD,FPPS
 I. OVERVIEW OF FUNGI
A. Fungi are eukaryotic organisms.
 Differences targeted by antifungals include:
 1. Fungal cells have cell walls (CWs).
 protect cells from osmotic shock, determine cell shapes, and have components that are
antigenic.
 composed primarily of complex carbohydrates (chitin with glucan and mannose-proteins)
 The CW glucan (not found in humans) is the antifungal target of the echinocandins like
caspofungin.
 2. Ergosterol is the dominant fungal membrane sterol rather than cholesterol, which is
an important difference targeted by imidazoles, triazoles, and polyenes antifungals.
 I. OVERVIEW OF FUNGI
B. Types.
 Fungi include organisms called molds, mushrooms, and yeasts
1. Hyphae - filamentous (tubelike) cells of molds (also known as the
filamentous fungi) and mushrooms.
 Hyphae grow at the tips (apical growth).
a. Septate or septations are cross walls of hyphae and occur in
great majority of the disease-causing fungi. They are referred to as
septate
b. Non septate or aseptate hyphae lack regularly occurring
cross walls. These cells are multinucleated and are also called
coenocytic. They often are quite variable in width with broad
branching angles
c. Hyphae may be dematiaceous (dark colored) or hyaline
(colorless).
d. Fluffy surface masses of hyphae and their “hidden” growth
into tissue or lab medium are called mycelia.
 I. OVERVIEW OF FUNGI
2. Yeasts are single-celled fungi, generally round to oval shaped They reproduce
by budding (blastoconidia).
3. Pseudohyphae (hyphae with sausagelike constrictions at septations) .
 Candida albicans is notable for developing into pseudohyphae and true
hyphae when it invades tissues
4. Thermally dimorphic fungi
 capable of converting from a yeast or yeastlike form to a filamentous form
and vice versa.
a. Environmental conditions such as temperature and nutrient availability
trigger changes.
b. They exist in the yeast or a yeastlike form in a human and as the
filamentous form in the environment.
“Yeastie beasties in body heat; bold mold in the cold.”
c. They include the major pathogens:
 Blastomyces, Histoplasma, Coccidioides, and Sporothrix in the United
States
 Paracoccidioides in South and Central America.
 I. OVERVIEW OF FUNGI

5. Fungal spores
 are formed either asexually or by a
sexual process involving nuclear fusion
andthen meiosis.
 a. Conidia are asexual spores of
filamentous fungi (molds) or mushrooms
 b. Blastoconidia are the new yeast
“buds”
 c. Arthroconidia are conidia formed by
laying down joints in hyphae followed
by fragmentation of the hyphal strand
 I. OVERVIEW OF FUNGI
C. Fungal nutrition.
 Fungi require preformed organic compounds derived from their environment.
 1. Saprobes live on dead organic material. Some are opportunistic, causing disease if
traumatically implanted into tissue.
 2. Commensal colonizers generally live in harmony on humans, deriving their nutrition
from compounds on body surfaces. Some are opportunists because under certain
conditions (e.g., reduced immune responsiveness) they may invade tissue or vasculature
and cause disease.
 3. Pathogens infect the healthy but cause more severe disease in the compromised
hosts. The damage to living cells provides nutrition. Most of these are also environmental
saprobes.
 DIAGNOSIS OF FUNGAL INFECTIONS
A. Clinical manifestations
B. Microscopic examination - rapid methods.
 1. Potassium hydroxide in a wet mount (KOH mount) of skin scrapings breaks down the
human cells, enhancing the visibility of the unaffected fungus
 2. A nigrosin or India ink wet mount of cerebrospinal fluid (CSF) highlights the capsule of
Cryptococcus neoformans but is very insensitive (misses 50% of cases).
 3. A Giemsa or Wright’s stain of thick blood or bone marrow smear may detect the
intracellular Histoplasma capsulatum.
 4. Calcofluor white stain “lights up” fungal elements in exudates, small skin scales, or frozen
sections under a fluorescent microscope, giving the fungus a fluorescent blue-white
appearance on a black background
 DIAGNOSIS OF FUNGAL INFECTIONS

C. Histologic staining: special fungal stains for fixed tissues

1. Gomori methenamine-silver stain: Fungi are dark gray to black against a
pale green background
2. Periodic acid-Schiff (PAS) reaction: Fungi are hot pink to red.
3. Gridley fungus stain: Fungi are purplish rose with a yellow background.
4. Calcofluor white stain
5. Immunofluorescent stains
 DIAGNOSIS OF FUNGAL INFECTIONS
D. DNA probes and nucleic acid amplification (NAATs) - for some systemic pathogens.
E. Cultures
 special media (e.g., Sabouraud’s dextrose medium),
 enriched media (e.g., blood agar) with antibiotics to inhibit bacterial growth
 enriched media with both antibiotics and cycloheximide (which inhibits many
saprobic fungi).
F. Fungal antigen detection uses known antibodies to identify circulating fungal antigens
in a patient’s serum, CSF, or urine.
G. Serologic testing done to identify patient antibodies specific to a fungus generally
requires acute and convalescent sera
 ANTIFUNGAL DRUGS
A. Polyene antifungals.
 bind to ergosterol in fungal membranes, creating ion channels, leading to leakage and
cell death.
1. Amphotericin B (AMB):
 administered intravenously (IV) for serious fungal infections and has been the drug of choice for
most life-threatening fungal infections.
 used in combinations with 5-fluorocytosine or fluconazole but only with very specific
fungi in specific body locales.
2. Nystatin
 is not absorbed from the gastrointestinal tract (used topically, intravaginally, or orally)
 Treats Candida overgrowth; infections of cutaneous or mucosal surfaces.
 ANTIFUNGAL DRUGS
B. 5-Fluorocytosine (5-FC, flucytosine).
 is an antimetabolite converted in fungal cells to 5-fluorouradylic acid, which
competes with uracil to cause miscoding and disruption of RNA, protein, and DNA
synthesis.
 resistance develops quickly if used alone
 used in combination with amphotericin B or fluconazole for cryptococcal meningitis.

C. Imidazole drugs are azole drugs with two nitrogens in the azole ring.
 They inhibit the lanosterol (14-a-demethylase interfering with ergosterol synthesis)
1. Ketoconazole -orally administered
 used only in non-life-threatening fungal infections.
2. Miconazole – used topically against dermatophytes and Candida spp.
 ANTIFUNGAL DRUGS
D. Triazoles are azole drugs with three nitrogens in the azole ring. They have better systemic
activity than the imidazoles.
1. Fluconazole:
a. Fluconazole has excellent oral bioavailability.
b. It is used for systemic infections, most commonly with Candida and Coccidioides,
2. Itraconazole:
a. This lipophilic imidazole drug is administered orally
b. It is used for treatment of mucocutaneous Candida infections, non-life-threatening
Aspergillus infections, moderate or severe histoplasmosis or blastomycosis, and sporotrichosis.
3. Voriconazole:
a. has a broad spectrum of activity with the exception of the nonseptate
fungi(Zygomycetes) but may be effective against other fungi that have developed AMB
resistance.
b. It is now a primary drug for the treatment of invasive aspergillosis as an alternative to
AMB.
4. Posaconazole is a newer azole licensed for treatment of Zygomycetes (nonseptate fungi)
infections.
 ANTIFUNGAL DRUGS
E. Echinocandins
 inhibit fungal glucan synthesis, thus leading to a weakened cell
wall and cell lysis.
 include caspofungin, micafungin, and anidulafungin.
 effective against Aspergillus spp., Candida spp., Pneumocystis
jiroveci, and a variety of other fungi.

F. Topical antifungals (imidazoles, allylamines: terbinafine and

naftifine, tolnaftate)
 may be used for dermatophytes and mucosal yeast infections.
 FUNGAL GROUPS
A few general group names are important.
 A. Zygomycetes (phycomycetes) are the nonseptate fungi.
Common genera are Mucor and Rhizopus.
 B. Dermatophytes are three genera of filamentous fungi causing
cutaneous infections: Trichophyton, Epidermophyton, and
Microsporum.
 C. Thermally dimorphic fungi in the United States are
Histoplasma, Blastomyces, Coccidioides, and Sporothrix.
 D. Dematiaceous fungi are darkly pigmented fungi.
Important Fungal Infections (Common or Serious)

BRS Microbiology Review 6th ed

I. SUPERFICIAL SKIN INFECTIONS
 I. SUPERFICIAL SKIN INFECTIONS
A. Pityriasis (tinea) versicolor.
 a fungal overgrowth in the stratum corneum
epidermidis, which disrupts melanin synthesis
 hypopigmented or hyperpigmented skin patches,
usually on the trunk of the body with little tissue
response.
 Epidemiology: Malassezia furfur
 also causes fungemia in premature infants on
intravenous (IV) lipid supplements.
 Diagnosis: potassium hydroxide (KOH) mount of
skin scales
 short, curved, septate hyphae and yeastlike cells
(spaghetti and meatballs appearance).
 I. SUPERFICIAL SKIN INFECTIONS
B. Tinea nigra.
 a superficial infection of the stratum corneum
epidermidis on the palmar or plantar surfaces
causing benign, flat, dark, melanoma-like lesions.
 It is caused by a dematiaceous (darkly pigmented)
fungus that produces melanin, which colors the skin.
 Hortaea werneckii formerly known as
Phaeoannellomyces werneckii, (formerly classified as
Exophiala werneckii and Cladosporium werneckii).
 Diagnosis is made on microscopic examination of
skin scrapings, mixed with potassium hydroxide
(KOH).
II. CUTANEOUS MYCOSES
II. CUTANEOUS MYCOSES
General aspects of cutaneous mycoses.
1. May be caused by any of the dermatophytes or Candida spp.
 Dermatophytes are a homogeneous group of filamentous fungi
 Epidermophyton, Microsporum, and Trichophyton. (cutaneous infections)
 Candida infections are more frequently mucocutaneous or in skin folds and
sometimes disseminate.
 Dermatophytes do not disseminate.
2. Skin, hair, or nails may be affected; infections are classified by the area of the body
involved.
3. Epidemiology:
a. zoophilic (animals) - cause lesions that are significantly inflammatory.
 Microsporum canis and Trichophyton rubrum.
b. anthropophilic (humans)- cause lesions that are less inflammatory.
 Epidermophyton floccosum and Microsporum audouinii.
 II. CUTANEOUS MYCOSES
4. Diagnosis:
 microscopic examination of skin, hair, or nail
material mounted in 10% KOH.
 unbranched hyphae sometimes with arthroconidia
 Selection of areas to sample in Microsporum
infections may be aided by the use of a Wood’s
(ultraviolet [UV]) lamp.
5. Treatment:
a. Lesions may become superinfected with bacteria
(presence of pus)
b. treatment with oral drugs if hair (and hair follicles)
are involved.
c. ID reaction: New sterile lesions may arise during
treatment.
 This hypersensitive state referred as the
dermatophytid (or “id”) reaction, a reaction to
circulating fungal antigens that indicates treatment
response.
 II. CUTANEOUS MYCOSES
A. Tinea capitis (ringworm of the scalp, skin, and hair).
1. Anthropophilic tinea capitis (gray patch):
 a. Occurs in prepubescent children and is epidemic, spread by
head gear, combs, and so forth.
 b. It is caused by Microsporum audouinii.
 c. It is usually noninflammatory and produces gray patches of hair.
2. Zoophilic tinea capitis (nonepidemic):
 a. Is transmitted by pets or farm animals.
 b. It is most commonly caused by Microsporum canis or by
Trichophyton mentagrophytes.
 c. It is inflammatory, often with boggy tender areas called kerion.
 d. Temporary alopecia, kerion, keloid, and inflammation may result.
3. Black-dot tinea capitis:
 a. This chronic infection occurs in adults and is characterized by hair
breakage, followed by filling of follicles with dark conidia.
 b. It is caused by Trichophyton tonsurans.
II. CUTANEOUS MYCOSES
B. Tinea barbae.
 an acute or chronic folliculitis of the beard, neck, or face
 caused by Trichophyton verrucosum.
 may produce pustular or dry, scaly lesions.
D. Tinea corporis.
 affects glabrous skin (non hairy)
 caused by T. rubrum, T. mentagrophytes, or M. canis.
 characterized by annular lesions with an active border that may
be pustular or vesicular.
E. Tinea cruris.
 acute or chronic fungal infection of the groin is commonly called
jock itch.
 accompanied by athlete’s foot or nail infections
 caused by E. floccosum, T. rubrum, T. mentagrophytes, or yeasts
like Candida.
 II. CUTANEOUS MYCOSES

F. Tinea pedis.
 commonly called athlete’s foot.
 caused by T. rubrum, T. mentagrophytes, or E. floccosum.
 three common clinical presentations:
 a. Chronic intertriginous tinea pedis (usually white macerated tissue
between the toes)
 b. Chronic dry, scaly tinea pedis (hyperkeratotic scales on the heels, soles,
or sides of the feet)
 c. Vesicular tinea pedis (vesicles and vesiculo pustules)
G. Favus (tinea favosa).
 highly contagious and severe form of tinea capitis with scutula (crust)
formation and permanent hair loss caused by scarring.
 Prophylaxis of all close contacts is needed.
 caused by Trichophyton schoenleinii. (Know this species! Permanent hair
loss!)
 occurs in both children and adults.
III. MUCOCUTANEOUS CANDIDIASIS/C. albicans
AND, OTHER SPECIES OF CANDIDA
 III. MUCOCUTANEOUS CANDIDIASIS/C. albicans
(AND, OTHER SPECIES OF CANDIDA)
A. General aspects of mucocutaneous candidiasis.
 1. Candida spp. are part of the normal flora of the skin, mucous
membranes, and gastrointestinal tract.
 2. Candida spp. are seen as yeasts on body surfaces.
 Normal colonization must be distinguished from infection when
Candida overgrows or invades the tissues.
 3. Candida albicans is seen in infected tissues as pseudohyphae,
true hyphae, blastoconidia, and yeast cells but is still referred to as
a yeast.
B. Oral thrush is a yeast infection of the oral mucocutaneous
membranes.
 1. It manifests as white curdlike patches in the oral cavity.
 2. It occurs in premature infants, babies on antibiotics, asthmatics
not using spacers with inhalers, immunosuppressed patients on
long-term antibiotics, and acquired immunodeficiency syndrome
(AIDS) patients which may extend through the gastrointestinal (GI)
tract (painful gastritis).
III. MUCOCUTANEOUS CANDIDIASIS/C. albicans
(AND, INCREASINGLY, OTHER SPECIES OF CANDIDA)
C. Vulvovaginitis or vaginal thrush.
 a yeast (Candida spp.) infection of the vagina that tends to
recur.
 manifests with a thick yellow-white discharge, a burning
sensation, curdlike patches on the vaginal mucosa, and
inflammation of the peritoneum.
 predisposed by diabetes, antibiotic therapy, oral contraceptive
use, and pregnancy.
 Diagnosis: KOH mount of “curd”
D. Cutaneous candidiasis involves the nails (increases with
prolonged use of false nails), skin folds of babies, obese individuals
(visible as creamy growth), or groin (but generally also the penis).
 Lesions may be eczematoid or vesicular and pustular.
 It is predisposed by moist conditions.
IV. SUBCUTANEOUS MYCOSES
 IV. SUBCUTANEOUS MYCOSES
begin with traumatic implantation fungus but remain localized in the cutaneous/ subcutaneous
tissues
A. Sporotrichosis (”rose gardener’s disease”) is caused by the dimorphic fungus Sporothrix
schenckii.
1. At 37°C S. schenckii grows as cigar-shaped to oval, budding yeasts;
 at 25°C S. schenckii grows as sporulating hyphae.
2. S. schenckii is found on plant materials such as roses, plum trees, or sphagnum moss and is
traumatically introduced by florist’s wires, splinters, or rose or plum tree thorns into subcutaneous
tissues.
3. generally not painful.
 When it spreads via the lymphatics (lymphocutaneous sporotrichosis), it produces a chain of lesions
on the extremities, with the older (lower) lesions ulcerating and the newer (upper) ones starting
nodular.
 4. Diagnosis: Clinical diagnosis is confirmed by culture; histology is generally negative.
 5. Treatment: itraconazole.
 IV. SUBCUTANEOUS MYCOSES
B. Eumycotic mycetoma.
 is a subcutaneous fungal disease characterized by
(1) swelling (tumefaction)
(2) sinus tracts erupting through the skin (if not treated)
(3) presence of “sulfur” granules (microcolonies) in the exudate.
 caused by Pseudallescheria boydii and Madurella species
 filamentous true fungi found in soil or on vegetation; entry is by traumatic implantation.
 usually occurs in rural, third-world agricultural workers in the tropics.
C. Chromoblastomycosis.
 one of a group of infections caused by dematiaceous (dark) fungi and seen in tissues
as pigmented, yeastlike bodies.
 It has colored lesions that start out scaly and become raised, cauliflower-like lesions.
(Blastomycoses may have similarly raised lesions.)
V. PNEUMONIAS/SYSTEMIC MYCOSES(CAUSED BY
FUNGAL PATHOGENS)
 V. PNEUMONIAS/SYSTEMIC MYCOSES(CAUSED BY FUNGAL PATHOGENS)

General aspects of pneumonias/systemic mycoses

 the three dimorphic fungal pathogens are Histoplasma, Coccidioides, and Blastomyces.
 are filamentous, grow in specific environments, and produce airborne spores that are inhaled into
alveoli to start infection.
 have true virulence factors and can cause disease in healthy individuals.
 cause a spectrum of disease in three basic forms:
a. Acute self-limited pneumonia, asymptomatic to severe, but generally self-resolving occurs in
healthy people.
 However, some organisms may survive in granulomas (as also happens in tuberculosis) and can
reactivate when the immune system becomes compromised later in life.
b. Chronic (generally pulmonary) disease generally occurs in debilitated people.
c. Disseminated infection occurs commonly in immunocompromised people or where a
large spore dose overwhelms the immune system.
 V. PNEUMONIAS/SYSTEMIC MYCOSES(CAUSED BY FUNGAL PATHOGENS)

A. Histoplasmosis/Histoplasma capsulatum
 a thermally dimorphic, facultative intracellular, fungal pathogen (with NO capsule).
 Epidemiology:
 endemic in the great river plains of the Ohio, Missouri, and Mississippi Rivers and the St. Lawrence
Seaway plus Latin America.
 found in soil enriched with bat or bird guano as hyphae with distinctive tuberculate macroconidia
and nondescript microconidia.
 The microconidia are of small enough size to enter the alveoli to start infection.
 Bat caves, old chicken coups, starling roosts, and so on, have high levels of spores.
 Histoplasma capsulatum has no capsule so it is misnamed.
 In stained smears, the yeasts’ cytoplasm shrinks away from the cell wall leaving a clear
space resembling a capsule.
 V. PNEUMONIAS/SYSTEMIC MY)COSES(CAUSED BY FUNGAL PATHOGENS

4. Histoplasmosis clinical symptoms:

 ranges from subclinical to severe pneumonia but self-resolves with bed rest and good
nutrition.
 Because Histoplasma’s yeast cells are phagocytosed by alveolar macrophages and
polymorphonuclear neutrophils (PMNs), the infected PMNs circulate in the blood so
thick blood smears and blood cultures are extremely useful for diagnosis,
 hilar lymphadenopathy and splenomegaly
 Th1 response and granuloma formation are critical to resolution, but as in TB, some
viable organisms may remain in granulomas.
 Disseminated histoplasmosis occurs in people with heavy spore exposure,
underlyingimmune cell defects (e.g., patients with AIDS, T-cell deficits, or lymphoma),
and children younger than 1 year of age who appear to have a defect in dendritic cell
function.
 V. PNEUMONIAS/SYSTEMIC MYCOSES(CAUSED BY FUNGAL PATHOGENS

C. Blastomycosis/Blastomyces dermatitidis (North America)

 is a thermally dimorphic fungus found as a filamentous fungus with small conidia in
rotting organic material including wood.
 are inhaled into alveoli where they transform into Blastomyces’s big, budding
yeasts with thick walls and broad bases on buds.
 clinical symptoms:.
 a. Acute pulmonary blastomycosis may not self-resolve, so even acute infections
are treated with itraconazole.
 b. Chronic pulmonary blastomycosis (coin lesions) may be misdiagnosed as
carcinoma.
 C. Disseminated blastomycosis may have bone and skin lesions
 V. PNEUMONIAS/SYSTEMIC MYCOSES(CAUSED BY FUNGAL PATHOGENS)
D. Coccidioidomycosis (valley fever)/Coccidioides immitis
 a thermally dimorphic pathogen that is endemic in California’s San Joaquin Valley and
the Lower Sonoran Desert of the southwestern United States and Mexico.
 In the lungs, inhaled arthroconidia develop into larger spherical, walled structures
called spherules with internal endospores.
 clinical symptoms:
a. Acute, self-limiting coccidioidomycosis is similar to acute histoplasmosis except that
erythema nodosum or multiforme are more likely.
 Persons with AIDS, pregnant women in the third trimester, Filipinos, African and Native
Americans, and certain other ethnic groups have an increased risk of dissemination.
 Itraconazole or fluconazole is used to treat individuals at high risk of dissemination.
b. Chronic coccidioidomycosis does not self-resolve.
c. Disseminated coccidioidomycosis -clinical presentation is similar to disseminated
histoplasmosis, with dissemination frequently to the meninges and mucous membranes.
VI. OPPORTUNISTIC MYCOSES
 VI. OPPORTUNISTIC MYCOSES
General aspects of opportunistic mycoses.
 range from annoying or painful mucous membrane or cutaneous infections
in mildly compromised patients to serious disseminated infections in severely
immunocompromised patients.
 caused by endogenous or ubiquitous organisms of low inherent virulence that cause
infection in debilitated, compromised patients.
 caused most commonly by Candida, Cryptococcus, Aspergillus, Pneumocystis, Rhizopus,
Mucor, and Pneumocystis
 may be life-threatening in compromised patients, they are rarely serious in well-nourished,
drug-free, healthy persons.
 VI. OPPORTUNISTIC MYCOSES
A. Candidiases- are the most common opportunists.
 may cause mucocutaneous infections or more serious infections involving the bronchi or lungs,
alimentary tract, bloodstream, urinary tract, and, less commonly, the heart or meninges.
 most common cause is C. albicans, but incidence of infections due to other species of
Candida is increasing.
 Predisposed individuals include very young or very old, those with wasting or nutritional diseases,
those who are pregnant or immunosuppressed, and those who have diabetes, a history of long-
term antibiotic and steroid use, indwelling catheters, or AIDS.
 Areas with excessive moisture like skin folds are also susceptible.
 Systemic candidiases are generally treated with fluconazole, lipid-based amphotericin B, or
capsofungin.
 Candidiasis clinical signs and symptoms.
a. Alimentary
b. Candidemias or blood-borne infections
 in patients with indwelling catheters or GI tract overgrowth and minor bowel defects; leading to
endocarditis or cerebromeningitis.
c. Bronchopulmonary infection occurs in patients with chronic lung disease; it is usually manifested by
persistent cough.
 VI. OPPORTUNISTIC MYCOSES
B. Malassezia furfur septicemia
 occurs primarily in premature neonates on intravenous lipid emulsions; it usually resolves if lipid
supplements are stopped.
C. Cryptococcal meningitis or meningoencephalitis/Cryptococcus neoformans.
 is a yeast that possesses an antigenic polysaccharide capsule.
 found in weathered pigeon droppings.
 Central nervous system (CNS) disease occurs most commonly in patients with Hodgkin’s
lymphoma, diabetes, AIDS (where it is the dominant meningitis), leukemias, or leukocyte enzyme
deficiency disease
 headache of increasing severity, usually with fever, followed by typical signs of meningitis and sometimes
personality changes.

 Diagnosis: diagnosed by cerebrospinal fluid (CSF) latex particle agglutination test for
Cryptococcus, India ink wet mount, and culture following lysis of white blood cells in CSF.
 Treatment: treated with amphotericin B plus 5-fluorocytosine or fluconazole.
VI. OPPORTUNISTIC MYCOSES
D. Rhinocerebral zygomycoses (also called phycomycoses or mucormycoses)
 caused by non septate fungi (phylum Zygomycota, genera Rhizopus, Absidia,
Mucor, and Rhizomucor).
 occurs in patients with acidotic diabetes or leukemia
 Clinical symptoms:
 facial swelling and blood-tinged exudate in the turbinates and eyes, mental lethargy,
blindness, and fixated pupils.
 Diagnosis: must be diagnosed rapidly, usually by a KOH mount of necrotic tissue or
exudates from the eye, ear, or nose.
 Treatment:
 (1) control of diabetes,
 (2) surgical debridement
 (3) aggressive treatment with amphotericin B or posaconazole.
 VI. OPPORTUNISTIC MYCOSES
E. Pneumocystis pneumonitis/pneumonia
 are infections caused by Pneumocystis jiroveci (formerly Pneumocystis carinii)
 Pneumocystis jiroveci has been reclassified as a fungus.
 It is an obligate fungal organism of humans (cannot be grown in vitro) but is extracellular,
growing on the surfactant layer over the alveolar epithelium.
 Radiographs show a patchy, diffuse appearance, sometimes referred to as a ground-
glass appearance.
 Pneumocystis jiroveci pneumonia (PCP):
 This pneumonia is responsible for approximately one-third of deaths in AIDS patients.
 causes morbidity and mortality when CD4+ counts decrease to less than 200/mm3 unless
prevented with prophylaxis.
 Diagnosis: diagnosed by microscopy of biopsy specimen or alveolar fluids
 Treatment: prophylaxis with trimethoprim-sulfamethoxazole or trimethoprim and
dapsone.
 VI. OPPORTUNISTIC MYCOSES
F. Aspergillosis/ Aspergillus fumigatus/Aspergillus flavus
 A major opportunistic human pathogen infecting immunosuppressed patients causing
invasive aspergillosis causing high mortality in AIDS and organ transplant patients
 MOT: inhalation of spores (respiratory system involvement)
 Clinical manifestations:
 Majority are asymptomatic except when disseminated
 prolonged antibiotic-resistant fever, invasive infection of the lung with respiratory symptoms
 CT scan shows characteristic halo and/or air crescent signs
 Diagnosis:
 Culture and microscopic examination: nonpigmented, septate hyphae with dichotomous
branching
 Asexual conidia are arranged in chains, carried on elongated cells called “sterigmata,” borne on
expanded ends (vesicles) of conidiophores
 Treatment and prevention:
 IV amphotericin and rifampicin
 The risk of infection can be greatly reduced by the use of high-efficiency particulate air (HEPA) filtration
 Types of infections

Superficial mycoses
Cutaneous mycoses
Mucocutaneous mycoses
Subcutaneous infections
Systemic mycoses:
A. Pathogens
B. Opportunists
 Superficial Infections
Pathogenesis Fungi produce enzyme keratinase to digest human keratin but cannot go deeper in
dermis
MOT Tinea is by direct skin-to-skin contact with an infected person, by sharing items with an
infected person, or by touching a contaminated surface (such as floors in shower and
locker rooms)
Disease Name Location and Description Diagnosis Treatment

Dermatophytes/ • Ring, wave red patches with central clearing Clinical Topical:
Ringworm • Non-hairy skin of the face, trunk, arms, or legs Scraping of
Tinea corporis • T. cruris- involvement of groin, erythema and lesion and Nystatin,
Trichophyton hyperpigmentation ( jock itch) examination Miconazole
Tinea pedis • Interdigital of toes and plantar area under Clotrimazole
( athlete’s foot) wood’s lamp ketoconazole
(UV)green
Tinea versicolor Round hypo ( white spot) or hyperpigmented patches fluorescence
Malassezia furfur in the skin, more superficial than dermatophytes

Tine capitis • a diffuse, itchy, scaling of the scalp resembling Griseofulvin

Tinea rubrum dandruff Shampoo
Trichophyton spp • especially common among children aged 3–9, Oral
Microsporum Antifungal
 Tinea Infections
 Tinea cruris
 Tinea rubrum
 Tinea capitis
 Tinea pedis
 Candidiasis in Children

Diaper/Napkin
dermatitis

 https://www.skinsight.com/skin-
conditions/infant/diaper-dermatitis-
candidiasis
Common Infections in Neonates and Infants
Candidiasis Candidiasis/ Yeast Infections
Common forms Oral candidiasis/ oral thrush Infectious diaper dermatitis
Congenital cutaneous candidiasis Invasive fungal dermatitis
Invasive candidiasis
Epidemiology 3rd most common cause of blood stream infection in newborn
Risk factors- prematurity, low birth weight, presence of venous catheter
Pathogenesis Decrease physiologic and defensive barrier to infections
Manifestation Oral candidiasis/ oral thrush- whitish curd like material/lesion in tonsillar faucet, palate or buccal
mucosa
Infectious Diaper dermatitis- confluent erythematous rashes in the perianal and peri-genital area
Congenital cutaneous candidiasis
Invasive fungal dermatitis- intertrigo in skin foldings of obese children
Invasive candidiasis- unstable temperature, lethargy, apnea, respiratory distress, abdominal
distention
Diagnosis Candida culture, microscopic exam as pseudohyphae
Treatment Localized candidiasis- Topical antifungal (Nystatin, Clotrimazole, Miconazole,
ketoconazole
Systemic candidiasis – IV Amphotericin B, Alternative Fluconazole, supplemented by
fluorocytosine
Prognosis Localized- responsive to topical systemic- high mortality
Candidiasis
 Moniliasis
Angular cheilitis
Oral Thrush
White Piedra
Jock itch

https://www.emedicinehealth.com/image-gallery/candidiasis_moniliasis_picture/images.htm
https://www.google.com/search?q=images+of+Tinea+cruris+in+adolescent&tbm=isch&ved=
2ahUKEwjszdqnwef3AhWSAaYKHRmSA4IQ2-cCegQIABAA&oq=images+
 Subcutaneous Fungal
Infections
Disease Chromoblastomycosis
Causative • Fonsecaea spp. – F. pedrosoi, F. compactum, F. dermatitidis, Phialophora spp
agent
Epidemiology tropical or subtropical disease, affecting mostly men as current or former farm workers,
often leaving disabling sequelae
Pathogenesis • initial cutaneous lesion at the inoculation site associated with fibrotic and
granulomatous reactions associated with micro-abscesses and often with tissue
proliferation secondary to cellular response to macrophages and Langerhan’s cells
• the presence of muriform (sclerotic) cells embedded in the affected tissue
MOT enter the skin by traumatic implantation
Manifestation • raised and crusted lesions of the skin
Diagnosis lesions show the presence of the fungus as round or irregular, dark brown, yeast-like
bodies with septate called sclerotic cells, which can be diagnosed in KOH mounts or in
sections and by culture on Sabouraud’s agar
Treatment itraconazole or terbinafine
Chromobastomycosis
( CBM)
Forms
 Mild -single lesion,
plaque or nodular type,
less than 5 cm in
diameter
 Moderate- single or
multiple lesion
verrucous
 Severe- covering large
area, multiple forms is a
combination of
different types

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063100/
 Subcutaneous Fungal Infections
Disease SPOROTRICHOSIS known as “Rose Gardener’s disease”
Causative • dimorphic fungus Sporothriz schenki, saprophyte found widely on plants, thorns, and
agent timber
• Sporothrix brasiliensis spreads through scratches or bites from animals, particularly cats
Epidemiology rare, no national statistic
Pathogenesis development on the skin, in subcutaneous tissue and in lymph nodes, of nodules which
soften and break down to form indolent ulcers
3 types: cutaneous ( skin) , pulmonary and disseminated
MOT from skin injection to lymphatics and causes a combination of pyogenic and
granulomatous reaction
Manifestation • Cutaneous - small, painless bump, developing from 1 to 12 weeks after exposure to the fungus
• Pulmonary- cough, shortness of breath, chest pain, and fever
• Disseminated - set of ulcerating nodules along a hard cord as it slowly grows up the lymphatics,
moves from distal to proximal and can lead to bone and joint destruction, exclusively in
immunocompromised individuals
Diagnosis culture mount of this fungus showing fine branching hyphae and pear-shaped conidia in
rosette like clusters at tips at lateral branches and singly along sides of hyphae
Treatment Oral Itraconazole , Supersaturated potassium iodide (SSKI) is treatment option for skin
sporotrichosis.
 Sporotrichosis
Management

Skin • Patients are well without fever
• Lesion develops at the site of a scratch
• Nodules appear under the skin along
the lymphatic channels
treated with saturated potassium iodide solution given
orally 3 times per day for 3-6 months until all lesions have
gone
Itraconazole orally for up to 6 months.
Oral terbinafine

Bones, joints • typically present with a subacute or Difficult to treat and rarely respond to potassium iodide.
chronic inflammatory arthritis involving one or more Itraconazole orally for months-1 yr Amphotericin IV if oral
joints therapy ineffective
• With or without skin lesions Surgery to remove infected bone

Lungs • Seen in severe underlying chronic lung disease Potassium iodide, itraconazole and amphotericin
• present with pneumonia Infected areas of lung may need to be surgically
• may or may not have skin lesions removed.

Disseminated ( with skin lesions, other organ involvement including the Itraconazole may be tried
CNS, kidney, eye, prostate, oral mucosa, larynx and brain Amphotericin plus 5-fluorocytosine
liver) occurs only in people with a weakened immune system,
HIV

https://dermnetnz.org/topics/sporotrichosis
 Systemic Fungal Infections
Endemic infections
 infect all types of people, including those with a normal immune system
 Histoplasmosis, Coccidiomycosis, Blastomycosis

Opportunistic Infections
 occur primarily in immunocompromised individuals, associated with high
rates of mortality
 Risk groups: cancer patients like leukemia and lymphoma, whole organ
transplant patients, patient’s with post op catheter, HIV infection, Burn
patients
 Invasive Aspergillosis, Invasive Candidiasis, Penicilliosis
 Systemic Fungal Infections
Disease Histoplasmosis
Causative • Histoplasma capsulatum
agent • mimics TB and has latent disease, histoplasmosis can cause pneumonia if inhaled into
nonperfused areas. It can cause a chronic, cavitating nodular infection very similar to
TB
Epidemiology it is found in some US states: Ohio-Mississippi Valley, the Caribbean, and Central and South
America
Pathogenesis fungus can be found in soil with high nitrogen content
MOT by inhaling spores, which change into yeast in the lungs, phagocytosed by macrophages,
and are disseminated hematogenously.
Manifestation • people with abnormal lungs, histoplasmosis can cause pneumonia if inhaled into
nonperfused areas. It can cause a chronic, cavitating nodular infection very similar to
TB
Diagnosis • 6 weeks from initial infection, test for histoplasmin antigen derivative similar to PTB
• differentiate between PTB and histoplasmosis, use sputum or blood smears, and
purified protein derivative (PPD)
Treatment Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12
weeks) is recommended for patients who continue to have symptoms for 11 month (B-III),
Methylprednisolone
 Histoplasmosis

➢Generalized nodule-ulcerative lesions

characteristic of chronic progressive
disseminated histoplasmosis

➢ Microscopic features of Histoplasma

Source: Chronic Progressive Disseminated Histoplasmosis in a Mexican Cockfighter

https://doi.org/10.4269/ajtmh.14-0086
 Systemic Fungal Infections
Disease Blastomycosis
Causative • Blastomyces dermatiditis
agent • a dimorph that lives in a soil as a mold and becomes yeast in the human host
Epidemiology Multiply in organic debris and locations with low humidity: woodlands, beaver dams,
marshes, and peanut farms
Pathogenesis
MOT Inhalation of spores and hematogenous route
Manifestation • Primary disease of the lung, nset is insidious resembling mild respiratory infections
low grade fever, chest pain and non-productive cough and gradually increase in
severity. Severe form is difficult to differentiate from active PTB – high grade fever,
night sweat, weight loss
• Disseminated Balstomycosis- causing skin disease (skin lesions behaving like skin
cancer), bone disease and urinary tract disease in men
Diagnosis • Microscopic examination of skin, scrapings, sputum, aspirates
• blastomyces is much bigger than histoplasma and has broad-based buds and a
small capsule, diagnosis similar to other fungi
Treatment Amphotericin B
Prognosis Cutaneous lesion is responsive but disseminated usually poor prognosis
 Systemic Fungal Infections
Disease Coccidiomycosis
Causative • Coccidiodes immitis
agent • dimorphic, occurring in the tissue as yeast and in culture as the mycelial form.
• Tissue form a spherule, 15–75 μm in diameter, with a thick doubly refractile wall
and filled with endospore
Epidemiology the most virulent systemic fungi, thrive in hot dry weather
Risk groups, HIV, those with immunosuppressant, pregnant women, filipinos and
Hispanic ethnic groups
Pathogenesis Once inhaled, the tissue reaction forma spherule- giant seedpod full of thousands of
yeast particles called endosperms, once ruptured form another spherules
MOT acquired by inhalation of dust containing arthrophores of the fungus
Manifestation • primary infection with Cocci can present respiratory symptoms and progress from
acute, sub acute and granulomatous reaction and fibrosis
• self-limited, flu-like syndrome (sometimes called Bali fever)
• CNS and Skin infections- severe form, fatal
Diagnosis • skin test for Cocci called coccidiodin.
Treatment Mild- Fluconazole, ketoconazole. Severe and Disseminated – Amphotericin B
Prognosis
Coccidiomycosis
Infection
 Severe cutaneous
disease from
disseminated
Coccidiomycosis
 Single skin lesion from
primary pulmonary form
 Erythema nodosum as
hypersensitivity reaction
from Cocciomycoses
antigen

https://www.msdmanuals.com/professional/infectious-diseases/fungi/coccidioidomycosis
 Aspergillosis
Pathogenesis

https://resident360.nejm.org/clinical-pearls/aspergillosis

Source: During Aspergillus Infection, Monocyte-Derived DCs,

Neutrophils, and Plasmacytoid DCs Enhance Innate Immune
Defense through CXCR3-Dependent Crosstalk
Retrieved from : https://www.sciencedirect.com/science/article/pii/S1931312820302535
 Systemic Fungal Infections
Disease Invasive candidiasis/Fungemia/ Neonatal Sepsis
Causative agent • Candidia albicans, C. Tropicalis ( inkeukemia and neoplasm)
• C. krusei ( use of intravenous catheters )
Epidemiology Usually in severely immunocompromised individuals
Pathogenesis colonization of budding yeast leading to cell –mediated immune response
MOT Varried, thru IV catheter seeding other organs, invasion of GIT
Manifestation • prolonged antibiotic-resistant fever, often associated with weight loss,
abdominal pain, and hepatic and/or spleen enlargement. CT scan may reveal
small radiolucent lesions in liver or spleen in patients with chronic invasive
candidiasis (hepatosplenic candidiasis
Diagnosis • Aspiration biopsy of skin lesion and microscopic examination
with histopathological appearance of nonpigmented, septate hyphae with
dichotomous branching
• CT scan shows characteristic halo and/or air crescent signs.

Treatment IV Amphotericin B and removal of catheter

Prognosis progressing to sepsis is usually fatal
 Systemic Fungal Infections
Disease Mucormycosis ( previously Zygomycosis)
C. agent • Rhizopus spp., Absidia spp., and Mucor spp
Epidemiology Rare but most mucormycosis infections are life-threatening
Risk groups are immunocompromised individuals and in presence of diabetic
ketoacidosis and neutropenia or hematologic malignancies
Pathogenesis • Present as rhino cerebral, pulmonary, gastrointestinal, or cutaneous mucormycosis
• Disseminated mucormycosis spread most frequently to the brain, with possible
metastatic lesions in the spleen, heart, and other organs
MOT contact with the fungal spores in the environment by inhalation infecting the sinus and
lungs or by skin breaks
Manifestation Gastrointestinal mucormycosis is more common among young children than adults.
and forms Premature and low-birth-weight infants less than 1 month of age are at risk if they have
had antibiotics, surgery, or medications that lower the body’s ability to fight germs and
sickness.6-7
Cutaneous (skin) mucormycosis occurs after the fungi enter the body through skin
break/ trauma after a burn, scrape, cut, surgery ( immunocompetent individuals)
Diagnosis • Culture, biopsy and histopathology of specimen
Treatment IV Amphotericin B, Posaconazole , Isavuconazole or oral, surgery to remove tissue
Prevention voriconazole prophylaxis, practice good hygiene in chidren
https://www.shutterstock.com/search/mucormycosis

Source: A retrospective analysis of eleven cases of invasive rhino-orbito-cerebral

mucormycosis presented with orbital apex syndrome initially. BMC Opthalmology Article.
https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-016-0189-1
 Opportunistic Fungal Infections/ Mycotic like Infections
Disease Actinomycosis
Causative • Actinomyces israelli
agent • Resemble like fungal infection but it is true bacteria
Epidemiology Uncommon in children but seen affecting infants, non-communicable
Pathogenesis Slow progressive suppurative infection by fistula formation
3 forms: cervicofacial, thoracic and abdominal

MOT and Cervicofacial- often proceeded by dental procedures, dental infections or minor trauma
Manifestations Presenting as indurating swelling or mass in the jaw, cheek or mandible, low grade fever
Thoracic- results from oropharyngeal secretions or from abdominal, initially with fever and minimal
coughing but eventually leads to abscess formation and empyema
Abdominal – usually from complication of appendicitis/appendectomy, perforating GI ulcers, or
penetrating trauma presenting as abdominal mass associated with fever, abdominal discomfort
and body malaise

Diagnosis • Culture isolation ( anaerobic and microaerophilic environment) and microscopic

exam of Gram positive mycelial filaments from specimen
Treatment IV Pennicilin or cephalosporin, alternative Erythromycin, clindamycin, tetracycline
Actinomycosis

https://www.medindia.net/patients/patientinfo/actinomycosis.htm

Source: Treatment of Cervicofacial Actinomycosis: A report of 19 cases and review of literature

Retrieved from: esearchgate.net/figure/Swelling-of-the-cheek-in-a-patient-with-actinomycosis-
Note-the-possible-beginning-of-a_fig1_236976734
 Opportunistic Fungal Infections/ Mycotic like Infections
Disease Nocardiosis
Causative • Nocardia asteroides
agent • Causes of pulmonary syndromes, Mycetoma and lymphocutaneous syndromes
Epidemiology Usually found in temperate environment, common in children and immunocompromised
host
Pathogenesis from initial infection ( 80% pulmonary) development of tissue reactions leading to
dissemination and death
MOT and Inhalation of dust particles and traumatic inoculation of skin
Manifestations Resembles other chronic pulmonary conditions ( like PTB, actinomycosis and other fungal
infection) presenting as fever, night sweats, malaise, productive cough, pleuritic pain,
and weight loss. Local extension develop empyema.
Diagnosis • Culture isolation (aerobic) and microscopic exam weak acid fast, gram staining of
sputum, pleural effusion or pus
• Radiology: most common findings of solitary lung abscess, necrotizing pneumonia,
and progressive nodular fibrosis
Treatment Sulfonamides and sulfadiazines, alternatives are ampicillin and erythromycin
Surgical drainage of empyema and abscesses
 Nocardiosis

Source: An Acute Nocardia Infection in a Pediatric Hand:

A case report Source: Primary cutaneous nocardiosis in children.
Retrieved from: https://www.sciencedirect.com/science Retrieved from: DOI 10.1099/jmmcr.0.000086
/article/abs/pii/S036350231731345X
 Systemic Fungal Infections
Disease Invasive Aspergillosis
Causative • Aspergillus fumigatus, Aspergillus flavus
agent • common cause of otomycosis and invading the lung tissues
Pathogenesis Disseminated aspergillosis involving the brain, kidney, and other organs in fatal
complication sometimes seen in debilitated patients on prolonged treatment with
antibiotic, steroids, and cytotoxic drugs
MOT Thru inhalation of spores

Manifestations • Majority are asymptomatic except when disseminated

• prolonged antibiotic-resistant fever, invasive infection of the lung with respiratory
symptoms
• CT scan shows characteristic halo and/or air crescent signs
Diagnosis • Culture and microscopic examination , histopathological appearance of
nonpigmented, septate hyphae with dichotomous branching
• Asexual conidia are arranged in chains, carried on elongated cells called
“sterigmata,” borne on expanded ends (vesicles) of conidiophores
• galactomannan detection for invasive aspergillosis
Treatment IV Amphotericin B combined with rifampicin
Prevention The risk of infection can be greatly reduced by the use of high-efficiency particulate