ID

Question 1

Why do critically ill patients get infections

Answer 1

Patient, ICU and organism factors.

Patient - Loss of barriers - ETT, cannulla, open wounds
Loss of immunity - drug induced, disease induced, poor nutrition

ICU - Overcrowding, multiple patients, Staff contacts

Organisms - Resistance higher as more Abx use, Higher rate of infection anyway

Question 2

Name some biomarkers of infection

Answer 2

Traditional - WCC, CRP
Pro-calcitonin - made in response to infection- Can rise 4 hours after bacteria emit
Bacterial PCR - for ribosomal RNA of a bacteria
Galactomannan/b-d glycan Glycan - fungal cell walls.
Galacto - aspergillus

Question 3

Why might a patient not respond to tx

Answer 3

Patient, Abx, Disease factors

PATIENT Immunosuppression (pathological - HIV, pharmacological - steroids)
Lack of source control. Enteral leak/ aspiration
Co-morbidity - lung ca impeding pneumonia

Abx - wrong one. Inadequate penetration., wrong dose/frequencyInactivation - lactamases```

DISEASE - the infection is not bacterial
It’s actually inflammation
No source control
New secondary Collection```

Question 4

How does critical illness affect abx

Answer 4

Absorption - gut oedema, gut function, blood splanchnic flow
Distribution - Vd alters, RRT, Protein binding - alters free drugs, acid base derangement
Extra corporal effects
Metabolism - hepatic metabolism. Biliary excretion, renal excretion

Question 5

How are abx drug regimes worked out

Answer 5

MIC (Cmax)
Effects depend on peak concentrations
Bolus drugs Gent/metronidazole

Time above MIC
Depends on time above the inhibitory concentration
Penicillins, carbapenem, lines, Clinda
Frequent dosing or infusions

Time and concentration dependent
Quinolones
Affected by the area under the curve above MIC

Question 6

Patterns of resistance

Answer 6

Inherent or acquired

Inherent - natural resistance. gram negative membrane impermeable etc

Acquired - modifications to genetic material

Mechanisms
Decreased penetration - cell has pumps actively pumping out abx
Alterations to the target site
Encoded by plasmids and transmissible between bacteria - horizontal transfer

Question 7

Types of antivirals

Answer 7

Guanosine analogues Aciclovir, gancyclovir
Neuraminase inhibitors oseltamivir, zanamivir

Question 8

Examples of guanosine analogues

Answer 8

Aciclovir - HSV, VSV
Gancyclo - CMV

Question 9

How guanosines work

Answer 9

Aciclovir - thymidine kinase turns aciclovir mono into triphosphate.Incorporates into viral DNA, leads to DNA chain termination
CMV has no thymidine kinase.
Gancyclo - CMV viral kinase, phosphorylates the virus

Question 10

Adverse effects of guanosines

Answer 10

Extravasated - thrombophlebitis and ulcers
Renal - crystallisation in tubules.
Neuro - tremors, confusion, seizures, coma
Gancyclo - bone marrow suppression

Question 11

Oseltamivir function

Answer 11

Neuraminidase inhibitors- Sialiac acid analogue, inhibits neuraominidsae on host cell

Question 12

Types of anti fungal

Answer 12

AzolesPolyenesEchinocandins

Question 13

Types of azole

Answer 13

Triazoles - flucon, voricon Imidazoles - ketocon

Question 14

Types of polyene

Answer 14

Amphotericin B

Question 15

Types of echinocandins

Answer 15

Caspofungin, micafungin

Question 16

Azoles active against:

Answer 16

Candida
Cryptococcus
Hisoplasma
SOME aspergillus (voriconazole)

Question 17

How do azoles work

Answer 17

Blocks synthesis of ergosterol, needed in the fungal membrane(BLocks 14a demethylation)

Question 18

How do polyenes worksUsed in:

Answer 18

Binds to ergosterol of cell wall, makes pores
Used aspergillus, candida, crytpo

Question 19

Name some echinocandins

Answer 19

Caspofuning

Question 20

How do echinocandins works

Answer 20

Inhibit 1,3 D-glucan synthase enzyme. Inhibits cell wall syntheses

Question 21

When are echinocandins used

Answer 21

Broad anti fungal| Less resistance to candida

Question 22

Define sepsis

Answer 22

A life threatening organ dysfunction caused by dysregulated host response to infection

Question 23

Define septic shock

Answer 23

Persistent sepsis induced hypotension, MAP<65mmHg after fluid resus and needing vasopressors ORLactate greater than 2 despite volume

Question 24

Outline pathophysiology of sepsis

Answer 24

Imbalance of pro and anti-inflammatory processes
Normal - foreign material found —> innate system activated, mast cels, NK cells.
Pro-inflam mediators (TNFa, IL1, ICAM1, VCAM1, NO) released.These expand beyond the site of localised site of infection —> widespread inflammation
Increased TNFa and IL1 — widespread inflammation
Complement activated — pro-coagulation, endothelial dysfunction,m micro vascular compromise, MOF.

Question 25

Thoughts on goal directed therapy

Answer 25

Rivers - single centre observational study which reduced mortalityNon blinded, so many interventions so which one worked.Really high mortality in the control arm.ARISE, PROMISE and PROCESS couldn’t replicateMortality is lower anyway.Maybe the things we learnt - early Abx and ICU admission are the things that make the difference

Question 26

Types of malaria

Answer 26

Plasmodium species
Falciparum
Malariae
Ovale
Vivax
Knowesi

Question 27

Diagnosis of malaria

Answer 27

Blood thick and thin films
Thick - high sensitivity
Thin - more specific and quantifiable