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Silverstein & Hopper (+ West) > Chapter 175 - Antimicrobial use in the critical care patient > Flashcards

Chapter 175 - Antimicrobial use in the critical care patient Flashcards

1
Q

What are the factors that increase the risk of infection with a multidrug- resistant microbe?

A
  • Previous antimicrobial exposure (within the last 3 months)
  • Invasive procedures
  • Longer duration of hospital stay (>5 days)
  • Inappropriate dosing regimens
  • Environment (community, hospital)
  • Immunosuppressive disease or therapy
  • Bacterial translocation from the GI tract
  • Placement of foreign materials with surfaces conductive to bacterial colonization (i.e. indwelling catheters)
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2
Q

What is the most common gram-negative commensal GI microbe?

A

E. coli

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3
Q

What is the most common gram-positive commensal GI microbe?

A

Enterococcus spp

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4
Q

How do organisms share genes imparting resistance?

A

Via integrins, plasmids, and transposons

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5
Q

What is the colony-forming units (CFU) limit after which we should anticipate resistance to any antimicrobial drug?

A

> 10^6 - 10^8 CFU whether the population is a commensal resident or an infecting pathogen

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6
Q

Give examples of problematic antibiotic-resistant pathogens

A
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Vancomycin-resistant S. aureus (VRSA)
  • Vancomycin-resistant Enterococcus
    (VRE)
  • Fluoroquinolone-resistant Pseudomonas (FQRP) and E. coli,
  • Fluoroquinolone-resistant Clostridium difficile
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7
Q

Define multidrug resistance

A

Resistance to three or more antimicrobial

drugs to which the organism is generally considered susceptible

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8
Q

In a teaching hospital, what were the doses of amoxicillin and enrofloxacin associated with expression of resistance to the treatment by fecal E. coli within 3 to 5 days of therapy?

A
  • Amoxicillin 10 mg/kg q12

- Enrofloxacin 5 mg/kg q24

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9
Q

Define nosocomial infection

A

Infection arising more than 48 hours after hospital admission

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10
Q

What are the 4 primary drivers that reduce the advent of antimicrobial resistance in health care environments (Centers for Disease Control and Prevention recommendations)?

A

(1) timely and appropriate initiation of antibiotics;
(2) appropriate administration and deescalation of antibiotics;
(3) data monitoring, transparency, and stewardship infrastructure;
(4) availability of expertise at the point of care.

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11
Q

T/F: Use of restrictive formularies to didacte the use of antibiotics are effective to reduce antimicrobial resistance

A

F

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12
Q

In human patients with septic shock, what is the survival rate’s decline for each hour’s delay in the administration of appropriate antimicrobial therapy after the onset of hypotension?

A

7.6%

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13
Q

T/F: The use of broad-spectrum antibiotics decreases the risk of resistance

A

F

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14
Q

What is the reported rate of incorrect empiric choices in treating patients in shock in humans?

A

About 50%

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15
Q

Which bacteria are more likely to be associated with:

  • Genitourinary tract
  • Abdominal infection
  • Granulocytopenic or otherwise immunocompromised patients
  • Deep isolated areas
A
  • Genitourinary tract: gram-negative aerobes
  • Abdominal infection: gram-negative aerobes, anaerobes
  • Granulocytopenic or otherwise
    immunocompromised patients: gram-negative aerobes
  • Deep isolated areas: anaerobes
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16
Q

T/F: Rational combination antimicrobial therapy can be a powerful tool for enhancing effectiveness while reducing resistance in the CCP.

A

T

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17
Q

What is the population size (CFU) of bacteria necessary for spontaneous mutations to happen and cause resistance to 2 drugs?

A

> 10^14 CFU

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18
Q

Why should we avoid to use bacteriostatic drugs in association with Beta-lactams?

A

Beta-lactams’ bactericidal activity depends on continued synthesis of bacterial proteins –> bacteriostatic drugs inhibit microbial growth = antagonistic effects

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19
Q

How do Beta-lactams and aminoglycosides act synergistically?

A

Beta-lactams induce cell wall failure and facilitate the penetration of aminoglycosides into the cell

20
Q

T/F: In humans, broadening the antimicrobial spectrum by combining at least two antimicrobials is recommended in patients with pneumonia

A

T

21
Q

What are the three major considerations that should influence our antibiotics dosing regimen?

A
  • The MIC of the infecting microbe
  • Its relationship to plasma and tissue drug
    concentrations achieved at the site of infection
  • The impact of microbial and host factors that impact active drug concentrations achieved at the site of infection
22
Q

What is MIC useful for? (2)

A

MIC data, is critical both to identify current bacterial resistance in patients at risk and to design an individual patient dosing regimen

23
Q

What is the meaning of a MIC that is very close to the susceptible breakpoint?

A

Some level of resistance has already begun to emerge in isolates classified as susceptible.

24
Q

What best define the efficacy of time-dependent antibiotics?

A

The time during which the plasma drug concentration is above the MIC

25
Q

What are the mechanisms of action that make antibiotics time-dependent drugs?

A
  • Cell wall inhibitors
  • Folic acid inhibitors
  • Drugs considered to be bacteriostatic.
26
Q

What is the recommended time during which the plasma drug concentration should be above the MIC for carbapenems?

A

25%

27
Q

Give 2 families of concentration-dependent antibiotics

A

Fluoroquinolones, aminoglycosides

28
Q

What is the recommended Cmax: MIC for concentration-dependent antibiotics? (Cmax target maximum concentration)

A

> 10-12

29
Q

What are the three levels of drug penetration (capillaries types and distribution) in normal tissues?

A
  • Sinusoidal capillaries (adrenal cortex, pituitary gland, liver, spleen) -> No barrier to bound or unbound drugs
  • Fenestrated capillaries (kidneys, endocrine glands) -> No barrier to unbound drugs
  • Continuous capillaries (brain, CSF, testes, prostate, muscle, adipose tissue) -> Barrier that preclude drug movement
30
Q

Why should we interpret MIC with caution for highly protein bound antibiotics if the infection affects the kidneys, brain, CSF, testes, prostate, muscle or adipose tissue?

A

MIC is determined in vitro in the absence of protein. The MIC may underestimate the total plasma concentration of unbound drug necessary for effectiveness (only form that can penetrate these organs through fenestrated and continuous capillaries)

31
Q

In tissues with fenestrated and continuous capillaries, is it more recommended to favor water-soluble or lipid-soluble antibiotics?

A

Lipid-soluble drugs.
Since these capillaries are not permeable to protein-bound drugs, lipid-soluble drugs are recommended to cross the phospholipid barrier and reach MIC more easily in these tissues

32
Q

Based on a human study, what is the percentage of β-lactams or aminoglycosides in plasma that reaches
bronchial secretions?

A

2 - 30% (water-soluble)

33
Q

Give one family of antibiotics that can accumulate in tissue and exceed the plasma concentration (useful in the presence of marked inflammatory debris).

A

Macrolides (i.e azithromycin concentration in bronchial secretions is 17-fold higher than plasma concentrations)

34
Q

Give two reasons for which a drug, even if excreted in the urine, may not be effective to treat a UTI

A
  • Drugs excreted in the urine may not concentrate there in the face of altered renal function
  • The drug may not be able to penetrate uroepithelial cells or biofilm protecting the organisms causing cystitis
35
Q

What factors can influence the distribution of a drug?

A
  • Tissue perfusion (i.e. shock)
  • Lipophilicity (lipophilic drugs have a larger volume of distribution)
  • Accumulation of fluid in peripheral tissues (i.e. interstitial edema, pleural and peritoneal effusion) which will increase the volume of distribution of the water-soluble drugs
  • Aggressive fluid therapy
  • Hypoalbuminemia (for protein-bound drugs but also because of peripheral fluid retention)
36
Q

Ideally, how should we monitor the antibiotics plasma concentration in critical patients with variable absorption, volume of distribution and elimination?

A

Peak serum sample collected 1 to 2 hours after administration and a second sample obtained 4 to 6 hours
–> So that both peak concentration (important for efficacy) and trough concentration (important for safety) can be predicted.

37
Q

In case of hypoalbuminemia, how should the dosage of antibiotics be adapted?

A

1.5 to 2-fold increase due to the increased volume of distribution

38
Q

What are the factors that influence elimination half-life? (2)

A 
Distribution
Clearance (depends on metabolism, drug interaction, GFR, renal function, lipophilicity)
39
Q

In general, is clearance decreased or increased in septic shock?

A

Increased due to the hyperdynamic state.

For any other critical illness, clearance is generally decreased.

40
Q

Give one family of antibiotics whose mechanism depends on oxygen tension

A

Aminoglycosides require aerobic active transport into the microbes

41
Q

What are the water-soluble antibiotics families?

A

Aminoglycosides, β-lactams and

glycopeptides

42
Q

What is the ‘‘inoculum effect’’?

A

This is the association between a large inoculum and the risk of therapeutic failure:

  • Larger inocula present more bacterial targets and thus require more drug molecules (higher doses).
  • Larger inocula present a greater risk of spontaneous mutations resulting in resistance
  • Larger inocula produce greater concentrations of destructive enzymes.
43
Q

Define biofilm

A

A biofilm is a community that effectively allows a single-cell microbe to become a multicell organism. It consists of microcolonies of both pathogenic and host microbes embedded in a polysaccharide produced by microbes adhering to surfaces. These include foreign bodies,
wound surfaces, or other tissues

44
Q

T/F: The biofilm formed on indwelling catheter is a good representation of the organisms infecting the tissues

A

F

45
Q

What is the most common toxicity associated with:
Aminoglycosides
Fluoroquinolones

A
  • Aminoglycosides: nephrotoxicity
  • Fluoroquinolones: retinal degeneration in cats / streptococcal toxic shock and necrotizing fasciitis in animals with Streptococcus canis
46
Q

When should we see clinical and microbiologic improvement after initiation of effective antibiotics?

A

Within the first 48-72 hours

Silverstein & Hopper (+ West) (84 decks)

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