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ECC boards > Sepsis/SIRS/MODS > Flashcards

Sepsis/SIRS/MODS Flashcards

1
Q

Which molecule brought by albumin is protective of the endothelial glycocalyx?

A

Erythrocyte-derived sphingosine-1-phosphate (Suppress matrix metalloproteinase)

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2
Q

What are components of the immunosuppression during sepsis?

A

Dysregulated compensatory anti-inflammatory response, lymphocyte exhaustion, increased tolerance to endotoxins, dyregulated expansion of T-regulatory cells

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3
Q

Name determinants of immunoparalysis in sepsis (6)

A 
Macrophage deactivation
Negative regulatory mediators
Increased apoptosis
Increased anti-inflammatory mediators
Altered energy uptake 
Suppression of immune cells
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4
Q

Name risk factors for antimicrobial resistance (6)

A

Antibiotic within the past 3 months
Environment with high frequency of resistance (Hospital, community)
Immunosuppressive therapy or disease
Bacterial translocation from GI tract
Invasive procedures
Placement of foreign material with surface conductive to bacterial colonization

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5
Q

Name the two bacteria that are the major part of GI microflora

A

Enterococcus (Gram +) and E.coli (Gram -)

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6
Q

Define MDR, XDR and PDR

A

MDR: Resistance to 3 or more antibiotic families to which the antibiotic is naturally susceptible
XDR: Sensitivity to only 1 or 2 antibiotics
PDR (Pandrug resistance): Resistance to all antibiotic families

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7
Q

Define a nosocomial infection

A

Infection that the patient acquired in the hospital, arising more than 48 hours after hospital admission, within a week of discharge or within a month of surgery

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8
Q

What is the decline in survival per hour of antibiotic delay in septic shock (people)?

A

7.6%

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9
Q

Which type of antibiotics can have antagonistic effects in combination therapy?

A

Combination of a drug that inhibits ribosomes (chloramphenicol, tetracycline, erythromycin) with a drug that relies on protein synthesis for the bactericidal activity (Beta-lactam, fluoroquinolone)

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10
Q

Give an example of a synergic antibiotic combination therapy

A

Ampicillin with gentamicin (Cell wall agent promote entry of gentamicin into cell) for enterococcus, enterobacter, pseudomonas and MRSA

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11
Q

What are three major factor to consider in the dosing regimen of antibiotics?

A

MIC of the infecting microbe
Plasma and tissue drug concentration and the site of infection
Impact of microbial and host factors impacting the drug concentration at site of infection

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12
Q

Time dependent antibiotic have a ___________ (reversible/irreversible) action on their target?

A

Reversible (Cell wall inhibitors, folic acid inhibitors, bacteriostatic atbs)

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13
Q

What is the appropriate magnitude of Cmax/MIC in concentration-dependent antibiotics?

A

10-12

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14
Q

What is the best measurement of effectiveness for concentration-dependent antibiotic? What value is associated with bacteria killing and decreased resistance?

A

Area under the inhibitory curve. AUIC >100-125 generally associated with bacterial killing and decreased resistance

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15
Q

What are the three levels (Blood vessel barrier) of drug penetration in normal tissues?

A

1) Sinusoidal capillaries; No barrier to bound or unbound drugs (Adrenal cortex, pituitary gland, liver and spleen)
2) Fenestrated capillaries; Pore permeable to unbound drugs (Kidneys, endocrine glands). **Protein bound drugs will not diffuse as well, and MIC might be underestimated (Doxycycline)
3) Continuous (Non-fenestrated); Tight junction prevent drug movement (Brain, CSF, testes, prostate, muscles)

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16
Q

____________ (lipid/water) soluble antibiotics penetrate better in organs with continuous capillaries?

A

Lipid (30-80% penetration vs 2-30% in bronchial secretion)

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17
Q

What are the two main causes of expansion of volume of distribution in critical patients?

A

Septic shock and trauma (Third spacing/edema)

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18
Q

What is the inoculum effect?

A

Larger inocula have a higher bacterial load/target, this require more drug molecules
Larger inocula have a greater risk of spontaneous mutation and produce more destructive enzumes

19
Q

How can nephrotoxicity to aminoglycoside be prevented?

A

1) Once daily administration with trough <1.2mg/ml
2) Hydration of patient
3) Morning administration (to promote drinking)
4) Avoid nephroactive drugs

20
Q

What are the benefit of antimicrobial de-escalation?

A

Cost minimization, reduction in adverse events, reduced risk of antimicrobial resistance, decreased incidence of infections related to antimicrobial use (C. difficile diarrhea, superinfection, fungal/Candida)

21
Q

Which families of antibiotics are included in beta-lactam antimicrobials?

A

Penicillin, cephalosporin, carbapenem

22
Q

What are two types of resistance against beta-lactam antibiotics?

A

Beta-lactamase produciton

Change in cell wall permeability (mecA gene modifies PBP2a in methicillin resistance)

23
Q

What are the benefits of meropenem over imipenem?

A

More soluble, less nephrotoxic, can be administered quicker

24
Q

What is the adaptive resistance of bacteria?

A

Capacity to decrease the update of an antibiotic after the first dose, more likely if low Cmax after administration (e.g. aminoglycoside and pseudomonas)

25
Q

What is the inhibitory quotient?

A

Cmax/MIC; Must be > 8-12 for effective bacterial killing of concentration dependent antibiotics

26
Q

What conditions can alter the volume of distribution?

A

Vascular leak syndrome, edematous states, hypoalbuminemia, SIRS, mechanical ventilation, extensive burns, severe trauma, aggressive intravenous fluid therapy, parenteral nutrition

27
Q

Name risk factors for aminoglycoside-induced nephrotoxicity?

A

Advanced age, duration of therapy, fever, volume depletion, dehydration, nephroactive drugs, preexisting kidney disease, potassium/magnesium depletion

28
Q

Name adverse events related to aminoglycoside administration

A

Neuromuscular paralysis- Interference with release and uptake of ACh in the NMJ and inhibition of calcium movement into the nerve terminal. Can be treated with calcium infusion or cholinesterase

Ototoxicity/vestibulocochlear toxicity

Nephrotoxicity: Uptake by proximal tubular cells and high concentration in lysosomes cause cell disruption. Single-daily-dosing and monitor for granular/cellular cast and proteinuria/glucosuria recommended

29
Q

What are strategies to avoid nephrotoxicity with aminoglycoside

A

1) Single daily dosing (In the morning)
2) Hydration of patient
3) Therapeutic drug monitoring with drug free interval of 2-4 hrs
4) Discontinuation of nephroactive drugs
5) Cautious use in patients with variable volume of distribution (Sepsis, edema, burns,…)

30
Q

What is the target of action for fluoroquinolone?

A

DNA gyrase (primary target) and topoisomerase IV

31
Q

Define postantibiotic effect.

A

Period of time after serum drug concentration falls below the MIC that bacterial growth continues to be inhibited
(E.g. fluoroquinolones, aminoglycosides)

32
Q

What are the mechanisms of resistance against fluoroquinolones

A

1) Mutation of the target- Gene mutation of DNA gyrase (Gram -) and topoisomerase IV (Gram +)
2) Increased expression of efflux pump (E. Coli and Salmonella)
3) Altering outer membrane porins to prevent passive diffusion of the drug into cytoplasm
4) Plasmid

33
Q

Fluoroquinolones have ___________ (higher/lower) concentration in lungs, bile, prostate and urine compared to serum.

A

Higher

34
Q

Fluoroquinolones are ________ (Ineffective/effective) against intracellular organisms,

A

Effective- Accumulation in neutrophils and macrophages, activity against mycoplasma, mycobacteria, chlamydia and brucella

35
Q

Administration of oral antiacids ________ (Increase/decrease/does not affect) absorption of fluoroquinolones and food ________ (Increase/decrease/does not affect) its absoprtion.

A

1) Decrease

2) Does not affect (but delays peak serum)

36
Q

How do fluoroquinolones cause seizures?

A

Inhibition of GABA receptors and stimulation of NDMA receptors

37
Q

How do fluoroquinolone cause cartilage damage in juvenile animals?

A

Inhibition of proteoglycans synthesis, chelation of magnesium, inhibition of mitochondrial dehydrogenase activity

38
Q

Name three major adverse events associated with fluoroquinolone use.

A
  • Seizures and neurological abnormalities
  • Cartilage defect in juvenile patients
  • Retinal degeneration and blindness in cats
39
Q

Name three major adverse events associated with fluoroquinolone use.

A
  • Seizures and neurological abnormalities
  • Cartilage defect in juvenile patients
  • Retinal degeneration and blindness in cats
40
Q

Which parameters are used for SIRS criteria?

A

Temperature
Heart rate
Respiratory rate
WBC count

41
Q

What are the parameters for SIRS criteria in dogs?

A

T <100.6 or > 102.6
HR >120
RR>20
WBC >16K, <6K or band >3%

42
Q

What are the parameters for SIRS criteria in cats?

A

T <100, > 104
HR <140, > 225
RR >40
WBC <5K or >19K

43
Q

What is the definition of sepsis based on Sepsis-3?

A

Life-threatening organ dysfunction secondary to an infectious process

44
Q

What is the definition of septic shock based on sepsis-3?

A

Life-threatening circulatory, metabolic and cellular dysfunction secondary to an infectious agent.
Clinically, requirement for vasopressor or lactate >2mmol/L despite normovolemia

ECC boards (4 decks)

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