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Intensive Care > Antibioitcs (Elizabeth Prentice) > Flashcards

Antibioitcs (Elizabeth Prentice) Flashcards

1
Q

What are the 4 D’s of antibiotic prescribing

A

Drug
- right drug for right bug

Dose
- Adequate exposure of bug to antimicrobial
–> PK:PD index
–> MIC
–> Therapeutic Drug Monitoring

De-escalation
- Laboratory defined infection

Duration
- for the right amount of time

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2
Q

Which study illustrated the importance of early antibioitcs and the golden hour

A

Kumar et al 2006

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3
Q

Does the concept of bactericidal vs bacteristatic antibiotics have a clinical role

A

Often, bactericidal agents are preferred for severe infections

However,
It ignores the role of the host
There is no absolute distinction, for some antibiotics the action depends on the organism and concentration

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4
Q

Describe the mechanism of action of cell wall synthesis inhibitors

A

Inhibit enzymes that form cross-linking of peptidoglycan in the cell wall (these are called PBP or penicillin binding proteins)

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5
Q

Classify the commonly used Beta-lactams

A

Penicilins
1. Pencillin G / Pipericillin
2. Amoxicillin/Ampicillin
3. Cephalosporins
4. Carbapenems
5. Combinations (beta lactamase inactivator)
- Amoxicillin/Clavulanate
- Piperacillin/Tazobactam

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6
Q

Describe the coverage of penicillin

A

PENICILLIN
Anaerobes: yes

Gram positive:
- Streptococci

Gram negative:
- (weak activity against Gram - H.Ifluenzae)

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7
Q

Describe the coverage of cloxacillin and flucloxacillin

A

CLOXACILLIN

Anaerobes: No

Gram positive:
-nStrep. species and MSSA

No gram negative cover

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8
Q

Describe the coverage of amoxicillin vs augmentin

A

AMOXICILLIN
Anaerobes: yes

Gram positive:
- Ampicillin sensitive enterococci
- Streptococci
- (weak activity against staphylococcus)

Gram negative:
- weak

AUGMENTIN
Anaerobes: yes

Gram positive:
- Ampicillin sensitive enterococci
- Streptococci
- Staphylococci

Gram negative:
- Haemophilus Influenzae
- Many Enterobacteriacae

Non-fermentors (Pseudomonas aeruginosa)
- NO COVER

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9
Q

Describe the coverage of piperacillin vs piperacillin/tazobactam

A

The same as Augmentin BUT:

Pipericillin also covers non-fermentors (Pseudomonas aeruginosa)

AND

PipTaz has some activity against organisms with cephalosporniases (e.g. Amp-C enterobacteriacae)

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10
Q

Describe the coverage of first generation cephalosporins and give example

A

CEFAZOLIN / CEPHALEXIN / CEFADROXIL

Anaerobes: No

Gram positive
- Strep and Staph only

Gram negative
- weak

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11
Q

Describe the coverage of 2nd generation cephalosporins and give example

A

CEFUROXIME

Anaerobes: No

Gram positive
- Strep and Staph only

Gram negative
- better than gen 1

Pseudomonas
- None

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12
Q

Describe the coverage of third generation cephalosporins and give example

A

CEFTRIAXONE / CEFOTAXIME

Anaerobes: Minimal

Gram positive
- Broad

Gram negative
- Broad

Pseudomonas: No

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13
Q

How are 4th and 5th generation cephalosporins different to 3rd generation cephaolsporins

Give example of 4th generation cephalosporin

A

CEFEPIME (4th)

Has the same broad cover as 3rd gen and also covers pseudomonas

CEFTAROLINE / CEFTOBIPROLE

Have the same cover as 3rd gen and also covers MRSA and CNS. Do not cover pseudomonas

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14
Q

Describe the cover of carbapenems and note specific advantages and disadvantages of certain drugs

A

Anaerobes: Yes

Gram positive
- broad
- Does not cover Enterococci, MRSA, CoNS

Gram negative
- Broad
- Does not cover CREs

Pseudomonas: Yes

EXCEPTIONS
Ertapenem - does not cover pseudomonas
Imipenem + cilastatin does cover enterococci

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15
Q

What are the Glycopeptides, what is their mechanism of action and what is their specific importance?

A

Glycopeptides
- Vancomycin
- Teicoplanin

Mechanism
- Inhibits cell wall synthesis

Spectrum
- All Gram positive (including G+ anaerobes) and importantly including MRSA and enterococcus faecium

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16
Q

How is Vancomycin Resistant Enterococcus treated

A

Linezolid
Daptomycin

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17
Q

What is the mechanism of action and spectrum of activity of Aztreonam

A

Mechanism
- Cell wall synthesis inhibition

Spectrum
- Gram neagative
- Pseudomonas

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18
Q

Describe how protein synthesis inhibitors work and list the common classes of antimicrobials that work like this

A

Act on Ribosomes
Multiple different agents that disrupt the protein synthetic processes that occur during transcription and translation.

  1. Macrolides
  2. Aminoglycosides
  3. Lincosamides (clindamycin)
  4. Linezolid
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19
Q

Describe the spectrum of activity of Mcrolides

A

Similar to amoxicillin

Importantly it is also effective against atypical organisms such as:
- Mycoplasma pneumoniae
- Chlamydia trachomatis
- Legionella pneumophila

and
- Mycobacterium avium complex

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20
Q

Describe how nucleic acid (DNA) synthesis inhibitors work and list the common classes of antimicrobials that work like this

A

Inhibit DNA gyrase, the enzyme responsible for coiling of the DNA

The Fluoroquinolones

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21
Q

What are the important side effects of the fluoroquinolones

A

Connective tissue weakness
- Aortic dissection
- Achilles tendon rupture

Increased risk of antimicrobial resistance

22
Q

Describe the spectrum of activity of ciprofloxacin. How does the spectrum of activity of Levofloxacin and Moxifloxacin differ from ciprofloxacin

A

CIPROFLOXACIN
Anaerobe: minimal

Gram positive
- minimal. Staph aureus only

Gram negative
- broad cover

Intracellular organisms
- Legionella pneumophila
- Chlamydia trachomatis

MOXIFLOXACIN
Covers what cipro covers but with a much bigger Gram positive cover.
No pseudomonas cover

LEVOFLOXACIN
Covers what cipro covers but with a much bigger Gram positive cover.
Covers Pseudomonas

23
Q

How do antibiotics that inhibit metabolic pathways work

A

Many differnt metabolic pathways can be disrupted by different antimicrobials.

Example:
Cotrimoxazole - inhibits Folic acid synthesis (enzymes). Folic acid is needed for nucleic acid synthesis

24
Q

How do inhibitors of cell membrane function work as antimicrobial agents. What is their spectrum of activity and give an example

A

They disrupt the phospholipid structure of the outer cell membrane of gram negative bacteria.

E.g. Colistin

Spectrum: Gram negative bacteria only including pseudomonas

E.g Daptomycin

Used for Vancomycin Resistant Enterobactericiae

25
Q

When is colistin reserved for multiresistant organisms?

A

Toxic. Generally used topically. No need for systemic use as antimicrobial resistance expands

26
Q

List the antibiotics classes by mechanism of action

A
  1. Cell wall synthesis inhibitors
  2. Protein synthesis inhibitors
  3. DNA synthesis inhibitors
  4. Metabolic pathway inhibitors
  5. Cell membrane function inhibitors
27
Q

Describe the 3 mechanisms for antimicrobial resistance

A

Intrinsic Resistance
- Innately resistant (e.g. Vanco no effect on Gram neg as the outer cell membrane is impermeable to glycopeptides)

Acquired Resistance
- Induced resistance (preveiously susceptible) now resistant due to mutation or insertion fo genetic material into genome

Adaptive resistance
- Indiced by environmental stressors like sub-inhibitory levels of antibiotics.

28
Q

List the ways that bacteria become resistant to antibiotics

A
  1. Target site alteration
    - Change to structure of PBP (e.g. MRSA. Also VRE and VRSA)
  2. Access to target site alteration (altered uptake or increased elimination of antimicrobial from the vicinity of the target site)
    - efflux pumps and altered outer membrane permeability - porin repression (gram negatives).
  3. Inactivating enzymes
    - B lactamases (ESBL)
    - Carbapenemases (CRE)
29
Q

What is a biofilm

A

Secretion of biofilm by colony of bacteria prevents detection by host defenses - thick sticky matrix also prevents penetration by antibiotics.

30
Q

What factors influence the choice of antibioitic

A
  1. Organism susceptibility
  2. Effect site concentration
  3. Collateral damage and side effects
  4. PKPD principles
31
Q

Define the MIC

A

Minimum Inhibitory concentration (MIC) is lab defined construct that is the lowes concentration of antibiotic that inhibitis growth of a strain of bacteria.

Lab techniques
1. Microdilution
2. Disk diffusion
3. Gradient Test (gradient strips)

The best antibiotic for the bug will be effective at the lowest MIC.

However, the MIC must be compared against a breakpoint to describe whether the bacteria is resistant, Sensitive or Intermediate when the antibiotic is administered in usual doses.

32
Q

What is the breakpoint

A

The breakpoint is a previously agreed upon concentration of antibiotic which defines whether a species of bacteria is susceptible or resistant to an antibiotic.

33
Q

What is the Mutant Selection window

A

This is when the antibiotic concentration lies between the Minimum Inhibitory concentration (MIC) and the Mutant Prevention Concentration (MPC) there is a higher chance of the emergence of resistance

The area on the graph between these lines on a concentration time axis is called the mutant selection window

34
Q

Summarise the penetration of Augmentin

A

CSF - Poor
Lung - Good
Soft Tissue - Good
Urinary tract - Fair

35
Q

Summarise the penetration of Ceftriaxone

A

CSF - Good (in high dose)
Lung - Good
Soft Tissue - Good
Urinary tract - Good

36
Q

Summarise the penetration of aminoglycosides

A

CSF - Poor
Lung - Poor (unless nebs)
Soft Tissue - Fair
Urinary tract - Good

37
Q

Summarise the penetration of Bactrim

A

CSF - Good
Lung - Good
Soft Tissue - Good
Urinary tract - Good

38
Q

Summarise the penetration of Ertapenem

A

CSF - Poor
Lung - Good
Soft Tissue - Good
Urinary tract - Good

39
Q

Summarise the penetration of meropenem

A

CSF - Good (in high doses)
Lung - Good
Soft Tissue - Good
Urinary tract - Good

40
Q

Summarise the penetration of Vancomycin

A

CSF - Poor
Lung - Fair
Soft Tissue - Poor
Urinary tract - Good

41
Q

Define Therapeutic Drug monitoring

A

Measurement of specific drugs at designated time intervals to optimise individual dosing regimens and achieve required PK/PD targets.

However, TDM measures serum concentrations and may not reflect the concentration at the effect site.

42
Q

Define and give examples of collateral damage during antimicrobial therapy

A

Unintended adverse effects on the ecology due to antibiotic use which manifests as the selecting out of, and development of colonization with, MDR pathogens.

E.g. Quinolones –> MRSA and resistant Pseudomonas
3rd gen cephalosporins –> C difficile, VRE, CRAB, ESBL Klebsiella

43
Q

Summarise the pharmocokinetic and pharmocodynamic properties of commonly used antibiotics

A
  1. Time dependent (time above MIC) - should be 100% above MIC for effective killing
    - Beta Lactams
  2. Concentration dependent (Cmax/MIC)
    - Aminoglycosides
    - Metronidazole
  3. Area under the concentration time curve (AUC 0-24h/MIC)
    - Vancomycin
    - Fluoroquinolones
44
Q

When should the peak levels of aminoglycosides be measured

A

30 minutes after the FIRST dose of aminoglycoside (NOT after 3 days)

Why - must give an appropriate dose from the beginning. Its too late if this is only picked up 3 days later

45
Q

How high above MIC do we aim to achieve for aminoglycosides which exhibit concentration dependent killing

A

10 - 12 above MIC

46
Q

The minoglycoside concentration falls with time (one dose in 24 hours). why does it continue to have an antimicrobial effect?

A

They exhibit a POST-ANTIBIOTIC EFFECT which is seen because the antibiotic is taken up into the organism which continues to exert its effect even though the serum concentration has fallen.

47
Q

Which antibiotics demonstrate a post antibiotic effect and what type PKPD mechanism of killing are these medications

A

Aminoglycosides
Metronidazole

Drug taken up by bacteria and continues to exert effect despite falling serum concentration.

48
Q

What are the major problems with under dosing antibioitcs

A
  1. Inefficient killing
  2. Compromised clinical outcome
  3. Non-lethal selection pressure for multi-drug resistant organisms
49
Q

Explain the impact of altered volume of distribution in septic patients

A

Lipophilic antibiotic drugs have intracellular accumulation and hepatic clearance so only maintenance dosing needs to be altered in hepatic dysfunction
- Fluoroquinolones
- Macrolides

Hydrophilic drugs is difficult in sepsis due to the increased volume of distribution and renal clearance. Additionally fluid administration and vasoplegia increase Vd. Therefore, more drug needs to be required to achive plasma (and therefore effect site) concentrations. This is only relevant for hydrophilic antibiotics.

Additionally hypoalbuminaemia mean higher free drug fraction which is filtered and removed at the kidneys

50
Q

What is the dose of the following in sepsis

Amikacin
Cefepime
Ceftazidime
Cloxacillin
Ertapenem
Gentamicin
Imipenem
Meropenem
Piptaz

A

Amikacin: 25 - 30 mg/kg daily (NOT 1g)
Gentamicin: 7 - 9 mg/kg daily (Not 320 or 400)

Cefepime 2g 8h
Ceftazidime 2g 8h
Cloxacillin 2 g 6 hrly. 3g 6hrly in Staph bacteraemia
Ertapenem 1 g 12 hourly

Imipenem 1g 8hrly
Meropenem 1 - 2 g 8 hourly
Piptaz 4.5g 6 hourly

51
Q
A

Intensive Care (22 decks)

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