ID Flashcards
Why do critically ill patients get infections
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
Name some biomarkers of infection
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
Why might a patient not respond to tx
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```
How does critical illness affect abx
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
How are abx drug regimes worked out
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
Patterns of resistance
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
Types of antivirals
Guanosine analogues Aciclovir, gancyclovir
Neuraminase inhibitors oseltamivir, zanamivir
Examples of guanosine analogues
Aciclovir - HSV, VSV
Gancyclo - CMV
How guanosines work
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
Adverse effects of guanosines
Extravasated - thrombophlebitis and ulcers
Renal - crystallisation in tubules.
Neuro - tremors, confusion, seizures, coma
Gancyclo - bone marrow suppression
Oseltamivir function
Neuraminidase inhibitors- Sialiac acid analogue, inhibits neuraominidsae on host cell
Types of anti fungal
AzolesPolyenesEchinocandins
Types of azole
Triazoles - flucon, voricon Imidazoles - ketocon
Types of polyene
Amphotericin B
Types of echinocandins
Caspofungin, micafungin
Azoles active against:
Candida
Cryptococcus
Hisoplasma
SOME aspergillus (voriconazole)
How do azoles work
Blocks synthesis of ergosterol, needed in the fungal membrane(BLocks 14a demethylation)
How do polyenes worksUsed in:
Binds to ergosterol of cell wall, makes pores
Used aspergillus, candida, crytpo
Name some echinocandins
Caspofuning
How do echinocandins works
Inhibit 1,3 D-glucan synthase enzyme. Inhibits cell wall syntheses
When are echinocandins used
Broad anti fungal| Less resistance to candida
Define sepsis
A life threatening organ dysfunction caused by dysregulated host response to infection
Define septic shock
Persistent sepsis induced hypotension, MAP<65mmHg after fluid resus and needing vasopressors ORLactate greater than 2 despite volume
Outline pathophysiology of sepsis
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.
Thoughts on goal directed therapy
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
Types of malaria
Plasmodium species
Falciparum
Malariae
Ovale
Vivax
Knowesi
Diagnosis of malaria
Blood thick and thin films
Thick - high sensitivity
Thin - more specific and quantifiable
