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PR3124 PT3 > Principles of Antimicrobial Use > Flashcards

Principles of Antimicrobial Use Flashcards

1
Q

What does “antimicrobial stewardship” means?

A

Careful & responsible management of antimicrobials through the use of a systematic approach.

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2
Q

List the steps of the systematic approach to antimicrobial use.

A

1) Indications for Abx
(a) Confirm presence of infection
(b) Identification of pathogens
2) Regimen (choice, ROA, dose, duration)
(a) Selection of antimicrobial & regimen
3) Monitoring & Plan
(a) Monitor response

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3
Q

What are some host factors that increase the risk of infection in an individual?

A

1) Disruption of natural protective barriers (innate immunity)
2) Age
- Young children -> Immature immune system
- Elderly -> Impaired & aged immune system
3) Immunosuppression
- Malnutrition
- Underlying diseases
- Drugs (i.e. immunosuppressants, chemotherapy, steroids)
4) Alterations to normal host flora

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4
Q

What are some localised subjective symptoms observed in patients with ongoing infections?

A

1) GI disturbances (N/V/D, abdominal distension)
2) Respiratory symptoms (cough, purulent sputum)
3) Urinary disturbances (dysuria, frequency, urgency)
4) Pain & inflammation at site of infection (erythema, swelling, warmth)
5) Purulent discharge (wound, vaginal, urethral)

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5
Q

What are some systemic subjective symptoms observed in patients with ongoing infections?

A

1) Fever, chills & rigours
2) Malaise / general tiredness
3) Palpitations
4) Shortness of breath
5) Mental status changes
6) Weakness

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6
Q

List some objective parameters used to help with the confirmation of a likely infection in an individual.

A

1) Vital signs
2) Laboratory test
3) Radiological imaging

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7
Q

What are some vital signs observed in an individual who is likely undergoing an infection?

A

1) Fever (Temperature > 38 degrees Celsius)
2) Hypotension (SBP < 100 mmHg)
3) Tachypnea (RR > 22 bpm)
4) Tachycardia (HR > 90 bpm)
5) Mental status (esp. in elderly) via drop in Glasgow coma scale

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8
Q

A patient is currently experiencing a fever of temperature above 38 degrees Celsius and does not display any other symptoms currently. Is there sufficient evidence to indicate Abx for this patient? Why so?

A

No! While fever is a hallmark of infection, there is a need to exclude other non-infectious causes of fever first.

Non-infectious causes of fever can include:

  • Cancer
  • Intracranial haemorrhage
  • Drug fever (i.e. beta-lactams, antiepileptics, anti-convulsants & allopurinol)
  • Hyperthyroidism & thyroid medications
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9
Q

Do inflammatory laboratory markers suffice as infection laboratory markers?

A

No

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10
Q

List the laboratory biomarkers used to indicate an infection in an individual.

A

1) Non-specific biomarkers
- Elevated or depressed total WBC (TW > 10 x 10^9 /L or TW < 4 x 10^9 /L)
- Increased neutrophils (% > 75%)
- Increased C-reactive protein (CRP) (infection > 40 mg/L)
2) Specific biomarkers
- Increased erythrocyte sedimentation rate (ESR)
- Increased procalcitonin (start Abx when > 0.5mcg/L)

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11
Q

At what concentration of procalcitonin should the use of antibiotics be encouraged in patients with ongoing infections?

A

> = 0.5 mcg/L

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12
Q

What are the conditions in which antibiotics should be discontinued in patients who had infections?

A

1) [procalcitonin] < 0.5 mcg/L
OR
2) Decrease by 80% from peak concentration

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13
Q

For a patient whose [procalcitonin] = 0.6 mcg/L, and shown to have decreased by < 80% from peak concentration, should the use of Abx be discontinued?

A

No. Continuation of Abx is encouraged when [procalcitonin] >= 0.5 mcg/L AND decrease in peak concentration < 80%.

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14
Q

Under what conditions should a change in Abx be considered in a patient suffering from an infection?

A

1) Increased [procalcitonin] compared to peak concentration
AND
2) [procalcitonin] >= 0.5 mcg/L

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15
Q

For a patient with chronic kidney disease who display signs of an infection, what should be considered when determining the need to initiate antibiotics?

A

Important to consider the trend of [procalcitonin], rather than absolute values.
- Compare pt. baseline [procalcitonin] against current values instead due to already elevated procalcitonin levels in CKD pt.

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16
Q

What should we look for when using radiological imaging to determine if a patient is currently infected?

A

Tissue changes, collections, abscesses & obstructions.

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17
Q

Why is it extremely important to obtain cultures before administering antimicrobials?

A
  • Follow-up cultures are much less reliable than pre-treatment cultures.
  • Empiric Tx may have been initiated & key pathogens may have been targeted already upon taking follow-up cultures.
  • Inability to narrow down / de-escalate Abx Tx
  • Development of Abx resistance
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18
Q

Differentiate between pathogens, colonisers & contaminants.

A

1) Pathogens: Capable of damaging host tissues & elicit host response, producing signs & symptoms of infection
2) Colonisers: Presence of normal flora & pathogenic organisms w/o eliciting host response
3) Contaminants: Typically acquired during collections/processing of host specimens w/o eliciting host response

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19
Q

Name a likely contaminant from blood culture.

A

1) Staphylococcus epidermidis

2) Bacillus spp.

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20
Q

Name a likely coloniser from urine culture.

A

Yeast

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21
Q

Explain the differences between empiric, definitive & prophylaxis antimicrobial therapy.

A

Empiric:

  • Microbiological results are NOT available
  • Abx use based on clinical presentation on likely site of infection, likely organism causing infection & likely susceptibility from antibiogram

Definitive/Culture-Directed:
- Abx use based on patient-specific microbiological (i.e. culture & susceptibility) results

Prophylaxis:

  • Infection prevention
  • E.g. surgical prophylaxis & post-exposure prophylaxis (STD, HIV)
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22
Q

What are the principles of antimicrobial use to achieve improved patient outcomes?

A

1) Timely initiation of appropriate agents (i.e. most effective, least toxic & narrowest-spectrum)
- Active antimicrobials should be administered ASAP esp. in severely ill pt.
2) Dosage individualised administration
3) Use Abx for shortest duration possible

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23
Q

What are the factors affecting the selection of antimicrobial agents to treat infections?

A

1) Host (patient) factors
2) Organism factors
3) Drug factors

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24
Q

Discuss the organism factors affecting the selection of antimicrobial agents.

A

1) Identity of infecting organism
- fungus, bacterium or virus?
- genus and species?
2) Susceptibility & resistance of infecting organisms
- Empiric: consider antibiogram
- Definitive: select active Abx according to AST
- Risk factor for multi-drug resistance
3) Consider combination therapy if required

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25
Q

What are the advantages of using combination Abx therapy?

A

1) Extend spectrum of activity
- Empirical or definitive Tx of polymicrobial infections (e.g. piperacillin-tazobactam + vancomycin for hospital-acquired pneumonia)
- Empirical Tx to cover all resistant strains of same organism (e.g. piperacillin-tazobactam + ciprofloxacin for P. aeruginosa ventilator associated pneumonia)
2) Achieve synergistic bactericidal effect
- e.g. ampicillin + gentamicin for Enterococcus endocarditis
- e.g. cotrimoxazole
3) Prevent development of resistance
- e.g. antimicrobial combinations against TB & HIV

26
Q

What are the disadvantages of using combination Abx therapy?

A

1) Increased risk of toxicity & allergic reactions
2) Increased risk of DDI
3) Increased cost
4) Selection of multi-drug resistant bacteria
5) Increased risk of superinfections (e.g. CDAD & fungal infections)
6) Concern for antagonistic effect (primarily antifungals -> amphotericin B & itraconazole)

27
Q

Discuss the host factors affecting the selection of antimicrobial agents.

A

1) Age
2) G6PD deficiency
3) History of allergy / ADR
4) Pregnancy or lactation
5) Renal / Hepatic impairment
6) Status of host immune function
7) Severity of illness
8) Recent antimicrobial use
9) Healthcare-associated risk factors

28
Q

Which classes of antibiotics are generally avoided in children?

A

1) Tetracyclines
- C/I: Children < 8 y/o
- ADR: discolouration of teeth & deposition in bones
2) Fluoroquinolones
- C/I: Children < 18 y/o
- ADR: arthopathy / joint abnormalities
3) Cotrimoxazole
- C/I: Newborns & infants < 2 months
- ADR: kernictus

29
Q

Which classes of antibiotics are generally avoided in patients with G6PD deficiency?

A

1) Sulphonamides (e.g. sulfamethoxazole & cotrimoxazole)

2) Nitrofurantoin

30
Q

Is the cross-sensitivity between penicillins & other beta-lactams attributed as a class effect that results in allergic reactions?

A

No. Cross-sensitivity is a result of the presence of similar side chains in the chemical structures of certain beta-lactams.

31
Q

Name three clinically relevant cross-reactivity reactions displayed by beta-lactams.

A

1) Penicillins G & V
2) Amoxicillin & ampicillin
3) Ampicillin & cephalexin
4) Cefepime & ceftriaxone
5) Ceftazidime & aztreonam

32
Q

Which beta-lactam(s) do(es) not display cross-reactivity with other beta-lactams?

A

Cefazolin

33
Q

Which classes of antibiotics are generally cautioned or avoided in pregnancy or lactation?

A

1) Tetracyclines
2) Fluoroquinolones
3) Cotrimoxazole (esp. first & last trimesters)
4) Nitrofurantoin (at term > 38 weeks)

34
Q

Which classes of antibiotics are generally safe in pregnancy and lactation?

A

Beta-lactams & macrolides

35
Q

Name two antimicrobials that are generally cautioned or avoided in patients with impaired renal functions?

A

1) Aminoglycosides
2) High-dose vancomycin
3) Amphotericin B

36
Q

Name two antimicrobials that are generally cautioned or avoided in patients with impaired hepatic functions?

A

1) Amoxicillin-clavulanate
2) Tetracyclines (tetracycline, doxycycline & minocycline)
3) Macrolides (erythromycin, clarithromycin & azithromycin)
4) 5-flucytosine
5) Triazoles (fluconazole, itraconazole & voriconazole)
6) Pyrazinamide

37
Q

Which classes of antibiotics are generally used in immunocompromised patients with infections?

A

Bactericidal:

1) Beta-lactams
2) Vancomycin
3) Aminoglycosides
4) Fluoroquinolones

38
Q

Which classes of antibiotics are recommended to treat MSSA infections?

A

1) Pencillinase-resistant penicillins (cloxacillin)

2) 1st gen cephalosporins (cefazolin & cephalexin)

39
Q

Which antibiotic(s) is/are recommended to treat MRSA infections?

A

Recommended: Vancomycin
Alternatives: Ceftaroline, tigecycline & linezolid

40
Q

Which classes of antibiotics are recommended to treat infections caused by Pseudomonas aeruginosa?

A

1) Anti-pseudomonal penicillins (piperacillin-tazobactam)
2) 3rd & 4th gen cephalosporins (ceftazidime & cefepime)
3) Carbapenems (imipenem-cilastatin & meropenem)

41
Q

Which classes of antibiotics are recommended to treat infections caused by ESBL-producing enterobacterales?

A

Carbapenems

42
Q

Which classes of antibiotics are generally avoided when treating infections caused by Enterobacter species? Why so?

A

3rd generation cephalosporins (ceftriaxone & ceftazidime)

  • may produce Amp-C beta-lactamases on exposure, leading to cephalosporin resistance
  • cefepime may retain activity
43
Q

Which antibiotic(s) is/are recommended to treat Bacteriodes fragilis infections?

A

Recommended: Metronidazole
Alternatives: Amoxicillin-clavulanate, piperacillin-tazobactam, carbapenems

44
Q

Which antibiotic(s) is/are recommended to treat Clostridiodes difficiles infections?

A

1) PO metronidazole (mild)

2) PO vancomycin (mild, moderate & severe)

45
Q

Which classes of antibiotics are recommended to treat CNS infections?

A

1) Pencillins
2) 3rd & 4th gen cephalosporins: ceftazidime, ceftriaxone & cefepime
3) Meropenem
4) Vancomycin (primarily for gram +ve infections)

46
Q

Which classes of antibiotics should NOT be used for CNS infections?

A

1) 1st & 2nd gen cephalosporins
2) Aminoglycosides
3) Macrolides
4) Clindamycin

47
Q

Which antibiotic is not used for pneumonia?

A

Daptomycin (inactivated by lung surfactant)

48
Q

Which antibiotics are drugs of choice for prostatitis?

A

Cotrimoxazole & ciprofloxacin

49
Q

List the classifications of antibiotics available based on their PK-PD characteristics. Name the parameter used in the classification of each category.

A

1) Concentration-dependent bactericidal killing (Cmax / MIC or AUC / MIC)
2) Time-dependent bactericidal killing with no persistent effect (T > MIC)
3) Time-dependent bactericidal killing with persistent effect (AUC / MIC)

50
Q

What does ‘post-antibiotic effect’ (PAE) refer to?

A

PAE is the ability of an antimicrobial agent to persistently suppress bacterial growth even at low or undetectable concentrations.

51
Q

Name a class of antibiotics that exhibits concentration-dependent bactericidal killing properties.

A

1) Aminoglycosides

2) Fluoroquinolones

52
Q

Name a class of antibiotics that exhibits time-dependent bactericidal killing properties with no persistent effect.

A

Beta-lactams (except ertapenem & ceftriaxone)

53
Q

Name a class of antibiotics that exhibits time-dependent bactericidal killing properties with persistent effects.

A

Vancomycin

54
Q

What is the dosing strategy for Abx exhibiting concentration-dependent bactericidal killing properties? Why so?

A

Optimise Cmax / MIC ratio, where peak is 8-10x above MIC

  • Usually means larger doses at extended intervals
  • i.e. once-daily high-dose administration

Possible benefits include maximised PAE, less nephrotoxicity, lowered cost due to minimal injections & prevention of adaptive resistance due to lack of continuous exposure.

55
Q

What is the dosing strategy for Abx exhibiting time-dependent bactericidal killing properties with no persistent effect?

A

Optimise %T > MIC, where the time at which [Abx] is above MIC is 40-70%

  • Usually means more frequent dosage administration
  • i.e. continuous IV infusion or prolonged intermittent infusion
  • can also block excretion with probenecid
56
Q

What is the dosing strategy for Abx exhibiting time-dependent bactericidal killing properties with persistent effects?

A

Optimise AUC / MIC ratio

  • Dependent on total daily dose
  • E.g. for vancomycin: target AUC / MIC ratio = 400-600
57
Q

Under what conditions are oral administration not recommended?

A

1) Absorption problems (e.g. GI pathology)
2) Suitable oral Abx unavailable (e.g. aminoglycosides & 4th & 5th gen cephalosporins)
3) High tissue concentrations are essential (e.g. endocarditis, meningitis, bone/joint)
4) Urgent Tx required
5) Patient non-compliance

58
Q

What does ‘collateral damage’ refer to?

A

Refers to the increased risk of microorganisms developing Abx resistance against other Abx outside of currently used Abx.

59
Q

Which antibiotic is known to be a CYP450 inducer?

A

Rifampicin

60
Q

Which classes of antimicrobials are known to be inhibitors of CYP450 enzymes?

A

1) Macrolides

2) Triazoles

61
Q

What are some possible reasons for an unsatisfactory response to antimicrobial therapy?

A

1) Inappropriate diagnosis (e.g. non-infectious causes, non-bacterial infections)
2) Inappropriate choice of agent (e.g. resistance or development of resistance)
3) Subtherapeutic concentration (e.g. non-compliance, improving renal function, DDI)
4) Collections or abscesses present -> require surgery or drainage
5) Impaired host defence
6) Superinfections
7) Drug toxicities

PR3124 PT3 (12 decks)

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