Oh’s (73) - Fungal Infections

Question 1

The difference between yeasts and moulds

Answer 1

Yeast - unicellular

Mould -multicellular

Question 2

Types of Invasive Fungal Infections

Answer 2

1) Primary Mycoses

Occur in immunoCOMPETENT
Endemic in places where spores are abdundant
Agent has innate virulence that overcomes normal host defences

2) Secondary / Opportunistic

Less innate virulence
But occur in immunocompromised, cancer, burns, HIV, Abx use

Question 3

Treatment options for fungal disease

Answer 3

Polyenes (Amphotericin B)

Azoles
Imidazoles and triazoles
(Voriconazole)

Echinocandins

Flucytosine

Question 4

Mechanism of action of polyenes

Answer 4

Amphotericin B

Bind to Ergosterol in fungal wall

Cell death

Question 5

Mechanism of action of Azoles

Answer 5

Inhibit ergosterol SYNTHESIS

Fungo-static

However - voriconazole can be fungicidal to aspergillus

Question 6

Mechanism of Echinocandins

Answer 6

Inhibit b-glycol synthesis
Cell wall becomes unstable

Fungicidal to yeasts
Fungostatic to asperigiullius

Question 7

Mechanism of flucytosine

Answer 7

Converts to 5 flurouracil
Incorporates into yeast RNA

Better with yeasts than moulds

Question 8

Other therapeutic options of fungal infections

Answer 8

Folic acid inhibition in Pneumocystosis

Question 9

Types of Priamry Mycoses

Answer 9

1) Blastomycosis (Gilchrist Disease) - Amphotericin for 12 months with Itraconazole step down
2) Coccidiodomycosis
3) Cryptococcous
4) Histyoplasmosis
5) Paracoccidiomnycosis

Question 10

Dispositions to Opportunistic Mycoses

Answer 10

Use of CVP lines
Cavity surgery
Neutropenia
Steroids
HIV
Disseminated malignancy
ICU > 7 days
TPN
Malnutrition
Burns
Organ transplant

Question 11

Types of Opportunistic Mycoses

Answer 11

Aspergillosis
Candida
Cryptococcosis
Penicillinosis 
Pneumocystosis
Zygomycoses

Question 12

Examples of Aspergillosis

Answer 12

Aspergillus genus of moulds

Fumigatus
Flavus
Niger

Question 13

Patients at risk of aspergillosis

Answer 13

Immunosuppresed - Chemo, HIV, steroids, transplant

ImmunoCOMPETENT - Liver disease, pancreatitis, DM
Chronic Lung disease on low dose steroids

Question 14

Define pulmonary aspergillosis

Answer 14

Spectrum from

Localised Simple Aspergilloma (may lead to BPF or bleeding through erosion()

To

Allergic Broncopulmonary Aspergillosis (asthma /CF)

To

Progressive multi site pulmonary disease with extensive destructive cavitation

Leads to systemic infection —> brain and solid organs

Question 15

Diagnosis Aspergillosis

Answer 15

Positive cultures/microscopy from samples

Focal lesions on CT chest/brain (halo sign)

Positive PCR - fluids (BAL), faster than MC&S, 90% sense/spec

Galactomannan

b-D-glucans in BAL or serum

Question 16

Treatment options of aspergillosis

Answer 16

Systemic Voriconazole

Alternative:
Liposomal Amphotericin B
Isavuconazole

Do not use echinocandins

Convert to oral voriconazole

Resection of pulmonary lesions
Interferon gamma

Question 17

Types of candida species causing invasive disease

Answer 17

Alibicans
Tropicalis
Galbrata
Krusei

Question 18

Early symptoms of invasive candidiasis

Answer 18

Fever, chills, malaise, dsypnoea

Localised - joint pain, visual impairment, neuorological disturbacne

Question 19

Diagnosis of candida

Answer 19

1) Positive cultures/microscopy
2) Focal lesions on CT chest, liver brain (lag behind serology testing)
3) . Positive PCR
4) Mannan Ag/Antimanna Ab
5) b-D-Glucan in BAL
6) PCR (limited)
7) ELISA for serum enolase and IgG to enolase (not widely available)
8) Uses of scoring systems - but these are better for saying who should NOT get treated.

Question 20

What is cryptococcosis and its mechanism of infection

Answer 20

C.neoformans, yeast found in soil and bird excrement.

Inhaled

If immuncomprimised - haematogenous spread, disseminated disease, CNS affinity

C.gattii causes infections in immunocompetent

Question 21

Diagnosis of cryptococcus

Answer 21

1) Positive serum cryptococcal antigen

2) MRI - dilated peri vascular spaces
Cryptococcomas - High signal in T2
40% of CT brains are normal

3) Tissue biopsy and microscopy - India Ink, Alcian Blue, Fontana-Masson
4) CSF sample, micro, biochem, cytology and cryptococcal antigen
5) CSF cultures 5 days on Saboraud Agar is CSF shows increased leucocytes

Question 22

Tx of cryptococcus

Answer 22

Liposoman Amphotericin B with combination flucytosine

Fluconazole 400mg/day 1-2 years in residual non-respectable disease

Posaconazole in CNS disease (crosses BBB)

Manage ICP with shunts./drain

Some benefit with dexamethasone

Question 23

Commonest pneumocystosis

Answer 23

PJP - Pneumocystis jirovecii

Fungus NOT a protozoan

But different from fungi as cell wall is cholesterol NOT ergosterol

Means that Amphotericin and azoles don’t work

Question 24

Populations at risk of PJP

Answer 24

Children - commonly have asymptomatic childhood infections

Impaired host immunity - CD4<200 (HIV)

Non-HIV - immunosuppression due to haem malignancy or transplant immunsuppresion

Previous CMV also predisposes (reduces T-helper)

Question 25

Symptoms of PJP

Answer 25

Non spec:
Malaise, dyspnoea, non-productive cough

Progress to:
Pyrexia, weight loss, exertion hypoxia

Minority get PTx

Question 26

Radiology in PJP

Answer 26

CXR - widespread infiltration from Hila
Occasional - localised infiltrative patterns and cavitation

HRCT - ground glass opacity

Question 27

Diagnosis of PJP

Answer 27

Based on history, risk factors, and radiology

40% pts have normal CXR

PJP DNA on PCR of a BAL +/- peripheral serum samples

OR

Immunoflurescene or silver staining of sputum

Question 28

Treatment of PJP and how it works

Answer 28

Co-trimoxazole

Inhibits folic acid synthesis by two pathways

High dose for 3 weeks

In HIV - co-admin of steroids:
When the A-a gradient is less the 4.6kPa

Question 29

Alternative treatments of PCP

Answer 29

Pentamidine
Clindamycine with Primaquine
Dapsone and trimethoprim
Atavaquone

Cases of Clinda + caspofungin