Fungal infections

Question 1

Sepsis

Answer 1

Circulatory system cannot meet demands of body due to:

• Infammatory mediators compromises integrity of blood vessels
• Leaky blood vessels lower bp
• Reduction of bp leads to hypoperfusion of lungs

Question 2

Guidance for fungal infections

Answer 2

• EORTC/MSG
• IDSA
• ESCMID
• BSCH 2008

Question 3

Candida spp.

Answer 3

Yeast
Normal gut flora
Diagnosed by cultures
Sources of infection: GItract and catheters
Important to know previous anti-fungal treatments

Question 4

Types of candidiasis

Answer 4

Catheter related
acute disseminated
chronic disseminated
deep organ (distant metastasis)

Question 5

Aspergillus spp

Answer 5

Mould

Common in environment and tends to cause pulmonary infections

Blood cultures are difficult to obtain so imaging and antibody detection is used instead

Question 6

Aspergillosis

Answer 6

Invasive aspergillosis

ABPA (allergic bronchopulmonary aspergillosis)

Aspergilloma (fungal ball) in preexisting cavity (such as with patients that have had TB. It is saprophytic

Question 7

Cryptococcus

Answer 7

Yeast

Most common is cryptococcus neoformans

Usually pulmonary infection or Invasive CNS

Especially common in HIV/AIDS?

Question 8

Histoplasma

Answer 8

Histoplasma capsulatam

Usually pulmonary and found in HIV/AIDS patients

Question 9

Diagnostic certainty

Answer 9

Diagnosis is often difficult so 3 classes of certainty:

Proven- fungal cause has been grown
Probable- 1 host, clinical and mycological
Possible- less criteria met than probable

These can vary dependant on species/site

Question 10

Diagnostic indicators in host

Answer 10

Unresponsive to ABx 
Neutropenia (neutrophil count down)
Immunosuppressed patients
HIV/AIDS
Prolonged use of corticosteroids

Question 11

Clinical diagnostic indicators

Answer 11

Relevant imaging
Resp: Lesion, air crescent sign, cavities
CNS: Lesions or meningeal enhancment
Disseminated: Target lesions liver/spleen

Indirect tests:
Galactomannan antigens
beta d glucan in serum

sputum and NBL

Question 12

Azoles

Answer 12

Imidazoles

Triazoles (flucanazole, itraconazole, posaconazole, voriconazole)

Question 13

Triazoles

Answer 13

Inhibits fungal CYP450 decreasing ergosterol production
Mostly fungastatic

Side effects: hepatic derangment and QT prolongation

Lots of interactions due to CYP450

Question 14

Fluconazole

Answer 14

Cheap af

Active against most candida and has CNS penetration

400-800mg daily depending on severity

CYP450 inhibition interactions

Question 15

Itraconazole

Answer 15

Better at prophylaxis of IFI’s

Better absorbed as liquid but tastes awful

Increased risk of hepatotoxicity and heart failure and has multiple interactions with CYP enzymes

Cannot give with atorvastatin and simvastatin

Question 16

Voriconazole

Answer 16

Excellent CNS penetration with 96% oral bioavailability

Generally used only for CNS infections

Visual disturbances due to administration

Question 17

Amphotericin

Answer 17

Binds to ergosterol in fungal cells and increases permeability. Is fungacidal

Broad spectrum but poor oral bioavailability therefore must be given IV. Start at 1mg/10min then watch for 30mins

Side effects of renal/cardio/hepato toxicity, electrolyte disturbances and infusion reactions

Question 18

Liquid formulations of amphotericin

Answer 18

Ambisome and abelcet

Significant reduction in renal toxicity

Tricky to prepareas low micron filters needed

Now first line over amphotericin B

Question 19

Echinocandins

Answer 19

Caspofungin- broad license and ok for renal impairment

Anidula fungin- used only for invasive candidasis, good for hepatic/renal failure

Question 20

Flucytosine

Answer 20

Nucleoside analogue of pyrimidine

Synergism with amphotericin but plasma levels must be done

Problems with resistance if used on its own

Conversion to 5-FU intracellularly and bone marrow suppression

Question 21

Dermatophytes

Answer 21

Moulds

Keratinophilic- infects hair/nails/skin most often
Spreads through direct contact and spores

Symptoms: itching, burning and pain

Tinea?

Question 22

Tinea corporis

Answer 22

Skin ringworm

Trichophyton rubrum

Question 23

Tinea cruris

Answer 23

Groin ringworm

Trichophyton rubrum/mentagrophytes
Epidermaphyton floccosum

Question 24

Tinea capitis

Answer 24

Scalp ringworm

Tricophyton tonsurans

Question 25

Tinea corpis/cruris treatment

Answer 25

Topical imidazol- Clotrimazol, miconazol or terbinafine
Topical corticasteroids used if infection severe

Oral therapy if topical doesn’t work:
Terbinafine 250mg daily (2-4wks cruris, 4 wks corpis)
Itraconazole 100mg daily 15days or 200mg for 7 days

Question 26

Tinea capitis treatment

Answer 26

Oral treatment- ketoconazole, selenium sulphide shampoo
Griseofulvin 1g daily 8-10wks + 2 weeks after symptoms improve. Effective against microsporum spp
Terbinafine 250mg daily 4wks. Effective against tricophyton

Question 27

Griseofulvin

Answer 27

1st antifungal
Narrow therapuetic range therefore only used in dermatophyte infections

Long courses necessary as it does not persist in keratinous tissue and should be taken with fatty foods

Side effects: alcohol like

Cannot use if hepatic impaired, pregnant or lupus

Question 28

Tinea pedis (athletes foot)

Answer 28

More common in adults, skin becomes scaled, macerated and fissuring

Caused by Trichophyton rubrum/mentagrophytes, Epidermophyton floccosum

Moccasin type athletes foot is less common

Question 29

Athletes foot treatment

Answer 29

Imidazole cream:2-4wks, Terbinfine cream 1 week

Oral treatment:
terbinafine- 250mg daily 2-6wks
itraconazole- 100mg 1x daily 30days/200mg 2xdaily 7days
griseofulvin- 500mg daily+2weeks after symptoms resolve

Question 30

Allylamine (Terbinafine)

Answer 30

Lipophilic so concentrated in keratinous tissue

Cannot use in pregnancy, hepato/renal impairment

Side effects: GI effects, headaches, hepatotoxicity, serious skin reactions (cease treatment), psychiatric effects

Interacts with rifapicin, OCP’s

Question 31

Onychomycosis (nails)

Answer 31

Trichophyton rubrum/mentagrophytes,Epidermophyton floccosum, Candida (rare)

DLSO most common type

Treat with terbinafine (250mg 6wks-3mths) or itraconazole (pulse treatment 200mg bd 7days every 21days) due to long retention in nails.Topical treatment is amorolfine 1-2x weekly for 6mths

Question 32

Pityriasis versicolor

Answer 32

Caused by malassezia furfur colonization of stratum corneum

Multiple patches on neck, trunk and shoulders appear-usually occurs around puberty

Treat with ketoconazole, selenium sulfide (topical)
Itraconazole 200mg daily for 7days

Seborrhoeic dermatitis may be extensive in immuno-compromised patients

Question 33

Oropharyngeal candidia

Answer 33

> 18yrs-oral fluconazole first line 50mg 1-2 weeks
2-18yrs-topical nystatin or miconazole
<2yrs- topical miconazole

Question 34

Genital candidiasis

Answer 34

One of the most common infections
Higher risk from: pregnancy, diabetes, broad spectrum antibiotics

symptoms: intense pruritis, pain upon urination/intercourse, adherent white plaques

Treat with: clotrimzole 10% 1-3days, fluconazole 500mg stat

Question 35

Cutaneous candidiasis

Answer 35

Under folds of skin
risk increased by antibiotics, HIV, skin conditions

causes pruritis, burning and pain

Treat with: skincare advice +topical imidazole or oral fluconazole 50mg 2-4wks if serious or topical fails