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Pharmacotherapy > Principles of antimicrobial use > Flashcards

Principles of antimicrobial use Flashcards

1
Q

What is the systematic approach to antimicrobial use?

A
  1. Confirm presence of infection
  2. Identification of pathogens
  3. Selection of antimicrobial and regimen
  4. Monitor response
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2
Q

What are data used in confirming presence of infection?

A

Risk factors for infections
Subjective evidence
Objective evidence
Site of infection (Possible source)

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3
Q

What are data used in identifying pathogens?

A

Likely pathogens

Microbiological tests

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4
Q

What do we consider when selecting antimicrobial and the regimen?

A

Emipiric, definitive or prophylaxis
Consider organism, host and drug factors
Decide Agent, ROA, regimen

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5
Q

What are key things in monitoring response?

A

Efficacy (therapeutic response)

Safety (ADRs)

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6
Q

What are some localized symptoms of infection? (subjective)

A 
D/V/N/abdominal distention
Cough/purulent sputum
Dysuria/frequency/Urgency
Pain and inflammation at site of infection
Purulent discharge
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7
Q

What are data used in confirming presence of infection?

A

Risk factors for infections
Subjective evidence
Objective evidence
Site of infection (Possible source)

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8
Q

What is the normal range of CRP and the factors that affect it?

A

Normal: <10mg/L
Mild inflammation/viral infection: 10-40mg/L
Active inflammation/bacterial infection: 40-200mg/L
Severe bacterial infection/burns: >200mg/L

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9
Q

What are key things in monitoring response?

A

Efficacy (therapeutic response)

Safety (ADRs)

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10
Q

What are some risk factors for infections?

A

Disruption of natural protective barriers
Age (very young/old)
Immunosuppression
Alteration in normal flora (i.e. hospital/use of abx)

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11
Q

What are some systemic symptoms of infection? (subjective)

A 
Feeling Feverish, chills, rigors
Malaise
Fast HR
SOB
Mental status changes
Weakness
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12
Q

What are things to note in identifying pathogens?

A

Take cultures before starting antibiotics
consider contaminant/colonizer/pathogen
consider Starting or Streamlining definitive therapy using susceptibility test results

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13
Q

What are the objective evidence of infection (labs)?

A 
Elevated WBCs (>10 x 10^9) or depressed WBCs (<4 x 10^9)
Increased neutrophils (note baseline)
Increased procalcitonin/CRP/erythrocyte sedimentation rate ESR (acute phase reactants)
Radiology
- X-ray (chest,bone)
- Ultrasound
- CT scan
- MRI
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14
Q

What are the key thresholds when using procalcitonin to STARTING antibiotics?

A
  1. <0.25ug/L: abx strongly DIScouraged
  2. Between 0.25ug/L (inclusive) to less than 0.5ug/L: abx DIScouraged (grey)
  3. Between 0.5ug/L (inclusive) to less than 1ug/L: abx encouraged
  4. 1ug/L or higher: abx strongly encouraged
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15
Q

What are the benefits of combination therapy?

A

Extended spectrum of activity (for polymicrobials or resistant strains)
Synergistic killing
Prevent development of resistance

  • i.e. pip-tazo (pseudomonas) + IV vancomycin (MRSA) for HAP
  • i.e. pip-tazo + cipro for pseudomonas
  • i.e. gentamicin + ampicillin for enterococcus endocarditis (synergism)
  • i.e. trimethoprim + sulfamethoxazole (synergism)
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16
Q

What are the key thresholds when using procalcitonin to STOPPING antibiotics?

A
  1. <0.25ug/L: STOPPING abx strongly encouraged
  2. Between 0.25ug/L (inclusive) to less than 0.5ug/L: STOPPING abx encouraged (grey)
  3. Between 0.5ug/L (inclusive) to less than 1ug/L: CONTINUING abx encouraged
  4. 1ug/L or higher: CONTINUING abx strongly encouraged
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17
Q

How can we determine the site of infection?

A

Clinical presentation
Risk factors
O/S evidences
Common sites: urinary tract, skin and soft tissues

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18
Q

Which kind of infections are likely to be anaerobic infections?

A

Intra-abdominal infections from perforated viscus (Bacteriodes, Clostridium)
Diabetic foot infections (polymicrobial process)

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19
Q

What should we note regarding wound swabs?

A

Usually superficial and carry alot of commensals

- But if there are no other results, we can cover all organisms and streamline therapy when pt is better

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20
Q

What does empiric therapy mean?

A

Microbiological results unavailable
Agent use based on clinical presentation, likely site of infection, likely organism and likely resistant pattern (antibiogram)

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21
Q

What are the disadvantages of combination therapy?

A

Increased toxicity and allergic reactions
Increased risk for DDI
Increased Cost
Selection for Multi-drug-resistant (MDR) bacteria
Increased risk of superinfections (fungal, CDAD)

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22
Q

What are some key host factors to note?

A 
Age
Allergies and ADR hx
G6PD deficiency
Pregnancy/Lactation
Renal/Hepatic impairment 
Immune status
Severity of infection
Recent antimicrobial use
Healthcare associated factors
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23
Q

Abx to avoid when pt has G6PD deficiency?

A

Sulfonamides and nitrofurantoin

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24
Q

Abx to avoid when pt is pregnant/lactating?

A

Fluroquinolones
Co-trimoxazole
Tetracyclines

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25
Q

Abx to avoid in children?

A

Fluoroquinolones

Tetracyclines

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26
Q

Abx to avoid in hepatic impairment?

A

Pyrazinamide

Augmentin

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27
Q

Abx to avoid in renal impairment?

A

High dose vancomycin

Aminoglycosides

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28
Q

Why are combination therapy and bactericidal abx recommended for immunocompromised patients?

A

More vulnerable to polymicrobial infections (combination therapy better covers these)
Bactericidal abx better help lower cell count (vs bacteriostatic)

29
Q

What are the abx consideration in severely ill pts?

A

Start active abx asap

Broader spectrum cover needed

30
Q

What are things to think about when pt has recent anti-microbial use?

A

Risk factor for drug resistant organism

If there was tx failure, avoid the same abx

31
Q

What are we referring to when discussing MDR organisms?

A

ESBLs producing gram negative organisms and MRSA

32
Q

What are healthcare associated risk factors?

A 
Hospitalization in the last 90 days
Current hospitalization (2 or more days)
Residence in nursing home
Antimicrobial use in last 90 days
Home infusion therapy (catheter risk factor for MRSA)
Chronic dialysis
33
Q

What are Drug Associated factors?

A 
Activity against suspected organism
Ability to reach site of infection
PK-PD characteristics
ROA
Side effect profile
Drug interactions
Cost
34
Q

Can ertapenem (carbapenem class) be used for pseudomonas?

A

No

35
Q

MRSA abx options?

A

Vancomycin, linezolid, daptomycin, ceftaroline

36
Q

Pseudomonas aeruginosa abx options?

A

3rd and 4th gen cephalosporins, pip-tazo, ciprofloxacin, AGs (gentamicin and amikacin), aztreonam, meropenem and imipenem

37
Q

ESBLs abx options?

A

Carbapenems (1st line), AGs

- FQs, Bactrim (co-trimoxazole) have increasing resistance rates, only for culture directed tx

38
Q

Anaerobe Cover?

A

Clindamycin, Metronidazole, Augmentin, Pip-tazo, carbapenems

39
Q

Can daptomycin be used for pneumonia?

A

No. It is inactivated by lung surfactant

40
Q

Should we use Aminoglycosides (AGs) for abscesses?

A

No. AGs are less effective in the low oxygen/pH, high protein environment. Prefer beta lactams

41
Q

Drug of choice for prostatitis?

A

Ciprofloxacin and Bactrim

42
Q

Drug of choice for CNS infections?

A

Penicillins (G and ampicillin), 3rd and 4th gen cephalosporins, meropenem and vancomycin

43
Q

Which abx cannot be used for CNS infections?

A

1st and 2nd gen cephalosporins, AGs, Clindamycin, macrolides

44
Q

Which abx feature concentration dependent killing?

A

Aminoglycosides, Fluroquinolones

45
Q

Which abx feature time dependent killing?

A

Beta lactams

46
Q

What is the Optimum Cmax/MIC or AUC/MIC ratio for concentration dependent kill?

A

8-10x above MIC

47
Q

Advantages of OD AG dosing?

A 
Concentration dependent kill
Post abx effect
Prevents adaptive resistance
Less nephrotoxicity
Lower labour/equipment cost
48
Q

What is the dose adjustment of AGs for renally impaired pts?

A

Increase the dosing interval without reducing dose

49
Q

What is the optimum Time above MIC for abx exhibiting time dependent kill?

A

40-70% of dosing interval above MIC

50
Q

What are some strategies for improve time above MIC?

A 
More frequent dosing 
Continuous IV infusion
Block excretion (i.e. probenecid)
51
Q

Which abx exhibits time-dependent bacterial kill with persistent effect?

A

Vancomycin

- Rate and extent of kill related to overall drug exposure (AUC) vs MIC

52
Q

What is the target AUC:MIC ratio for vancomycin treating MRSA?

A

400-600

53
Q

Why is the PO route favored over other ROA?

A 
Less need for line/injections and lowers blood infection risk
Avoids thrombophlebitis (iv needles can cause vein irritation)
54
Q

What are some situations where PO is not preferred?

A 
Absorption problem (GI issue)
No suitable PO abx
High tissue conc needed (i.e. meningitis, endocarditis, bone/joint infection)
Urgent tx needed
Non-compliance
55
Q

Examples of abx with good oral bioavailability?

A

Co-trimoxazole, fluoroquinolones, metronidazole, linezolid

56
Q

Can carbapenems be used together with valporate?

A

No. Carbapenems reduce the conc of valporate, potentially leading to pt seizures

57
Q

What are some CYP450 inhibitors?

A

Azoles and macrolides

58
Q

What are is an example of an CYP450 inducer?

A

Rifampicin

59
Q

Expected abx duration for surgical prophylaxis (Chlamydia cervicititis)?

A

24h or single dose

60
Q

Expected abx duration for UTI/Respiratory/Skin tx?

A

5-14 days

61
Q

Expected abx duration for endocarditis/osteomyelitis?

A

4-6weeks

62
Q

Expected abx duration for tuberculosis (chronic suppression)

A

6 Months

63
Q

Expected abx duration for HIV?

A

life long

64
Q

What is monitored under therapeutic response?

A

Resolution of s/sx
Microbiological eradication
Absence of complications/progression of infection

65
Q

Common ADRs for abx to monitor for?

A

Allergies (rash, itch, angioedema)

66
Q

When should we think of modifying/streamlining therapy?

A

When test results are available

When pt shows good clinical response

67
Q

Some reasons for poor clinical response?

A 
Wrong drug
Wrong dose/conc
Wrong organism
Wrong treatment (i.e. should have I&amp;D for abscesses)
Wrong diagnosis
Impaired host defense 
Toxicity of drug
Non-compliance
Improving renal function and clearance
Resistance
68
Q

When do we evaluate initial abx response?

A

48-72h later

Pharmacotherapy (10 decks)

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