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PR3151 Principles of Antimicrobial Use > Principles of Antimicrobial Use > Flashcards

Principles of Antimicrobial Use Flashcards

1
Q

What are the 4 key steps in the systematic approach to antimicrobial use?

A
  1. Confirm presence of infection [INDICATION]
  2. Identification of pathogens [INDICATION]
  3. Selection of antimicrobial and regimen [REGIMEN]
  4. Monitor response [MONITORING]
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2
Q

Step 1: Confirm presence of infection

What are the parameters to consider?

A
  1. Risk factors: disruption of the protective barriers of the innate system , immune function, age, alteration in normal flora that promotes overgrowth of microorganisms due to use of antibiotics or uncontrolled blood sugar
  2. Subjective (symptoms): localized and systemic
  3. Objective (signs):
    Vital signs
    fever >= 38
    Hypotension <100mmHg
    Tachypnea RR >22bpm
    Tachycardia HR>90bpm
    Change in mental status (Glasgow coma scale)

Lab test
Elevated/depressed WBC (4-10 X 10^9 /L)
Incr neutrophils (45-75%)
Incr CRP (<10mg//L, in infection >40mg/L)
Incr ESR (more utility for bone and joint infection)
Incr procalcitonin

Radiological imaging
Tissue changes, collections, abscess, obstruction

  1. Site of infection
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3
Q

Step 1: Confirm presence of infection

Why is procalcitonin more useful than CRP?

A

It is more specific for bacterial infection and can reflect severity of infection, used to supplement clinical assessment, guide initiation and discontinuation of antibiotics

Initiation cut off: <0.25ug/L, if stricter <0.5ug/L
*antibiotic is strongly discouraged when PCT <0.25ug/L

Discontinuation: <0.25ug/L OR decrease by >= 80% from peak conc. given <0.5ug/L

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4
Q

Step 1: Confirm presence of infection

When is a second PCT conc. obtain? (1st one obtain in early stage of episode)

A

6-12h later

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5
Q

Step 1: Confirm presence of infection

Other than bacteria infection, Procalcitonin may also be elevated in:

A
  • ESRF (since it is cleared by the kidneys)
  • Traumatic brain injury (TBI)
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6
Q

Step 2: Identification of pathogens, indication for antibiotic

Cultures should be obtained before administering antimicrobial because follow-up cultures are less reliable. Why is this so?

A

Follow up cultures may not reflect initial causative organisms
Follow up cultures can cause false negative

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7
Q

Step 2: Identification of pathogens, indication for antibiotic

What is the difference between pathogen, coloniser, and contaminant?

A

Pathogen: organism capable of invading host tissue, elicit host response, can be acquired from environment or due to normal flora invading other tissues

Coloniser: presence of normal flora or pathogenic organisms without eliciting host response

Contaminants: presence of microorganism acquired during collection/processing of host specimen, no host response
=> proper collection and handling of specimen is impt (e.g., take midstream urine, draw blood after proper disinfection)

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8
Q

Step 2: Identification of pathogens, indication for antibiotic

Mixed growth is often due to ________

A

Colonization
Not likely to be pathogen since good ecology still present, unlikely for one to cause infection

E.g., mixed growth of skin commensals + gram-negative bacilli
*gram-negative bacilli likely represent superficial colonisation or post-antibiotic flora

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9
Q

Step 2: Identification of pathogens, indication for antibiotic

What are some considerations to determine if its a pathogen?

A

Is it usually found at the site

Is it single huge inoculum or mixed growth

Is it isolated from multiple cultures/specimens

Any signs of invasion of the tissue

Signs and symptoms

Epidemiology, likelihood of causing disease

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10
Q

Step 3: Selection of antimicrobial regimen

What to consider?

A
  1. Empiric, definitive (culture-directed), or prophylaxis
  2. Which agent, route, dosing, duration
  3. Consider organism, host, drug factors
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11
Q

Step 3: Selection of antimicrobial regimen

Empiric therapy is based on ______, while definitive therapy is based on ________

A

Empiric: clinical presentation of likely site, likely susceptibility (antibiogram, drug spectrum of activity), consider pt risk factor for MDR pathogens (e.g., recent antibiotic use)

Definitive: based on susceptibility (culture and AST results)

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12
Q

Step 3: Selection of antimicrobial regimen

What are some organism factors?

A
  • Identify organism
  • Susceptibility/resistance of the infecting organism
  • Assess need for combination therapy
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13
Q

Step 3: Selection of antimicrobial regimen

For combination therapy, we look at the time-kill curve (log10 CFU over time) of the drugs to determine indifference, synergy, and antagonism. (and choose synergy)
Explain these.

A

Indifference: combi shows no diff in time to kill
Synergy: combi shows decrease in time to kill, more effective
Antagonism: combi is less effective than single drug

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14
Q

Step 3: Selection of antimicrobial regimen

When might we consider using combination therapy (advantages)?

A

To achieve synergistic bactericidal effect

To extend spectrum of activity:
- to cover all resistant strains of the organism esp when no 1 agent has susceptibility close to 100% (for empiric)
- when it is a polymicrobial infection (empiric/definitive)

To prevent development of resistance
- for combinations against M. tuberculosis and HIV (since they multiply quickly, and develop resistance at faster rate)

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15
Q

Step 3: Selection of antimicrobial regimen

What are some disadvantages of combination therapy?

A
  • incr risk of toxicity + allergic reaction
  • incr risk of DDI
  • incr cost
  • selection of MDR bacteria (incr selection pressure)
  • incr risk of superinfections (CDAD, fungal)
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16
Q

Step 3: Selection of antimicrobial regimen

What are some host factors that can affect selection of antimicrobial regimen?

A
  • age (dosing, prevalence of organism, antibiotic CI in children)
  • G6PD deficiency (cotrimoxazole, sulfonamide, nitrofurantoin)
  • history of allergies and ADRs (consider cross-reactivity as well)
  • pregnancy or lactation (safety of drug in pregnancy or fetus, changes in PK of antibiotics)
  • renal or hepatic impairment (dose adjustment, toxicity)
  • immune function status
  • severity of illness
  • recent antimicrobial use (in last 6 months, risk factor for drug resistant organism)
  • healthcare associated risk factors
17
Q

Step 3: Selection of antimicrobial regimen

Cross reactivity of penicillins and other B-lactams is due to allergic rxn between B-lactams with similar R1 side chain.

Give examples of B lactams with common shared R1 side chain.

A

Amoxicillin, Ampicillin, Cephalexin
(Cephalexin cannot be used with the aminopenicillins)

Cefepime, Ceftriaxone

Ceftazidime, Aztreonam

18
Q

Step 3: Selection of antimicrobial regimen

Which B lactam has no shared side chain?

19
Q

Step 3: Selection of antimicrobial regimen

What are some drug factors that can affect selection of antimicrobial regimen?

A
  • spectrum of activity
  • reach site of infection (e.g., able to penetrate CSF to treat CNS infections)
  • bactericidal vs bacteriostatic (bactericidal when MBC is within one 2 fold dilution of MIC)
  • PK-PD
  • route of administration (site and severity, IV vs Oral)
  • side effects (ADRs and infirect effects such as superinfection, collateral damage - development of resistance against other antibiotics - fluoroquinolone cause resistance to 3rd gen cephalosporin)
  • drug interactions
  • duration of use (specify review or stop date)
  • cost
20
Q

Step 3: Selection of antimicrobial regimen

How is PK-PD used to predict outcomes?

A

Use serum conc. (PK profile) and MIC to predict clinical outcome:

If conc. dependent: Cmax/MIC ratio
Optimise: Cmax 8-10x MIC
e.g., aminoglycoside (also has PAE), fluoroquinolones

If time dependent with no PAE/with short half-life: %T above MIC
Optimise: 40-70% of dosing interval above MIC
e.g., B-lactams

If time dependent with PAE/with long half-life: AUC24h/MIC ratio
Optimise overall drug exposure, AUC = (F . Dose) / CL
e.g., vancomycin

21
Q

Step 3: Selection of antimicrobial regimen

PK-PD drug factor, what is PAE?

A

Post antibiotic effect - ability of antimicrobial agent to persistently suppress bacterial growth even at low conc.

22
Q

Step 3: Selection of antimicrobial regimen

Why are conc. dependent antibiotics dosed at larger dose at extended intervals?

A

Maximize efficacy while limiting toxicity
Allow downtime that prevent adaptive resistance
Lower cost
If PAE - drug can still have effect at low conc.

23
Q

Step 3: Selection of antimicrobial regimen

What is Hartford nomogram used for?

A

Use conc. of sample drawn 6-14h after administration to determine the dosing interval for TDM of conc. dependent antibiotics.

24
Q

Step 3: Selection of antimicrobial regimen

How should dosing for aminoglycoside be calculated?

A

Aminoglycoside is hydrophilic, follows water

Hence,

Use TBW if TBW =< 130% IBW

Use AdjBW if TBW > 130% IBW, in order to deduct additional adipose tissue weight
AdjBW = 0.4 (TBW - IBW) + IBW

25
Q

Step 3: Selection of antimicrobial regimen

ORAL route of administration is preferred unless:

A
  • Absorption problem (e.g., GI pathology)
  • Oral not available
  • High tissue conc. required (e.g., endocarditis, meningitis, bone/joint)
  • Urgent treatment
  • Non-compliance
26
Q

Step 3: Selection of antimicrobial regimen
Drug factors
What are some drug interactions based on PK interactions?

A

A:
- impaired absorption of tetracycline/fluroquinolone due to divalent/trivalent cations => form non-absorbable chelates
- antacid and PPI decrease absorption of itraconazole, isoniazid, ethambutol
- erythromycin has prokinetic effect (motilin agonist) can reduce absorption of other drugs

M:
- CYP450 inhibitors: macrolides, azoles, isoniazid
- CYP450 inducers: Rifampicin
- Substrates, metabolised by CYP450: Voriconazole, Terbinafine, Metronidazole

E
- Probenecid inhibits tubular secretion of penicillins, increase penicillin conc. (prolong its effect)

27
Q

Step 4: Monitor response

What are the 2 treatment goals?

A
  1. Achieve therapeutic response
    - Resolution of symptoms and signs
    - Microbiological clearance
    - Absence of complications/progression
  2. Minimal adverse drug reactions
28
Q

Step 4: Monitor response

Why is clinical response evaluate after 48-72h?

A

Give antibiotic adequate time to work before evaluation

29
Q

Step 4: Monitor response

When should therapy be modified?

A
  • When empiric not effective (escalate to broader spectrum)
  • When AST available (de-escalate to narrowest spectrum possible)
  • When response satisfactory (switch from IV to oral, consider stopping)
  • When response unsatisfactory (re-evaluate)
30
Q

Step 4: Monitor response

What are some possible reasons for unsatisfactory response?

A
  • inappropriate diagnosis (non-infectious cause)
  • inappropriate choice of agent, resistance to agent
  • subtherapeutic conc. (due to non-compliance, DDI, improving renal function)
  • collections or abscess
  • impaired host defense
  • superinfection
  • toxicity of drug
31
Q

What are the 3 main principles of Antimicrobial use to achieve improved pt outcomes?

A
  1. Narrowest Spectrum
  2. Individualized dosage
  3. Shortest duration
32
Q

Daptomycin is not used for ______ as it is inactivated by _______

A

Not used for pneumonia, inactivated by lung surfactants

*Daptomycin: gram positives inlcuding MSSA, MRSA, VRE, Strep
*NOT used for Strep pneumoniae

PR3151 Principles of Antimicrobial Use (3 decks)

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