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Antibiotic > Principle of antimicrobial usage > Flashcards

Principle of antimicrobial usage Flashcards

1
Q

Outcomes of Antimicrobial Resistance

A

1) infections become more difficult to treat
2) require use of more expensive and toxic abx
3) Increase length of hospital stay
4) increase health care cost
5) increase morbidity and mortality

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2
Q

What we can do to prevent abx resistance

A

1) prevent infections by ensuring hands, instruments and environment are clean (alcohol cleaning)
2) Keep pt’s vaccination up to date
both are infection prevention

3) test to confirm if pt need abx treatment
4) only Rx and dispense abx when truly needed
5) Rx and dispense the right abx and at right dose and duration
(these are antibiotic stewardship)

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3
Q

Systematic approach to antimicrobial use

A
  1. Confirm presence of infection (indication for antibiotics)
    •Risk factors for infections
    •Subjective evidence
    •Objective evidence
    •What is the (possible) site of infection
  2. Identification of pathogens
    •What is the (likely) pathogen
    •Any microbiological test sent or results available
  3. Selection of antimicrobial and regimen
    •Empiric, definitive or prophylaxis
    •Consider organism, host and drug factors
    •Decide on choice of agent, route, dosing and duration of treatment
  4. Monitor response
    •Therapeutic response
    •Adverse drug reactions
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4
Q

Risk factors for infection

A

1) confirm Presence of infection (indication for abx)
•Age
- Very young -Immature immune system
- Very old -Impaired immune system with ageing

•Immunosuppression

  • Malnutrition
  • Underlying diseases (hereditary or acquired)
  • Drugs (e.g., chemotherapy agents, steroids, immunosuppressants)

•Disruption of natural protective barriers

  • Skin/mucous membrane
  • Cilia of respiratory tract

•Alterations in normal flora of the host
(So more resistance one will grow)
- E.g., in hospital or use of antibiotics

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5
Q

Subjective evidence

A

1) confirm Presence of infection (indication for abx)
•Localised symptoms:
- Diarrhoea, nausea, vomiting, abdominal distension -
- Dysuria, frequency, urgency
- Pain and inflammation at site of infection –erythema, swelling, warmth
- Purulent discharge (wound, vaginal, urethral)
- Cough, purulent sputum

•Systemic symptoms:

  • Feverish, chills, rigors
  • Fast heart rate
  • Malaise
  • Mental status changes
  • Shortness of breath
  • Weakness
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6
Q

Objective evidence

A

1) confirm presence of infection

A) Vital signs:
- Fever (Temperature ≥ 38 degC)
•Hallmark of infection
•May be masked by use of anti-pyretics
•Non-infectious causes of fever eg cancer,
intracranial hemorrhage, drug fever

  • Hypotension (SBP < 100 mmHg)
  • Tachypnea (Respiratory rate > 22 bpm) (norm: 12-18)
  • Heart rate (> 90 bpm) (norm: 72bpm)
  • Mental status (especially in elderly) (e.gdrop in Glasglowcoma scale)
B) Lab test: 
•Elevated or depressed total white 
(TW >10 or < 4 x10^9/L) 
•Increased neutrophils 
•Increased procalcitonin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)
  • Radiology:
    • X-ray (chest, bone)
    • Ultrasound
    • Computerized tomography (CT)scan
    • Magnetic resonance imaging (MRI)MRI
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7
Q

CRP Levels

A

Normal individual
- usually <10mg/L

Minor CRP elevations
- 3-10mg/L

Generally
- mild inflammation and viral infections: 10-40mg/L
- Active inflammation and bacterial infection
: 40 - 200mg/L

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8
Q

Procalcitonin guideline

starting and stopping

A

[] < 0.25ug/L = Abx strongly discourage
[] 0.25 - 0.49ug/L = Abx discourage
[] 0.5 - 0.9ug/L = Abx encouraged
[] >= 1 = Abx Strongly encouraged

obtain second procalcitonin [] 6-12hr later if blood sample taken for calculation was at early stage of episode

[] < 0.25ug/L = stop abx strongly encourage
[] 0.25 - 0.49ug/L OR decreased by >= 80% from peak []
= Abx stoppage encouraged

[] >= 0.5 OR decreased by <80% from peak []
= Continue abx encourage

[] >= 0.5 OR increase peak [] = changing Abx Strongly encouraged

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9
Q

What is the possible site of infection

A

1) confirming presence of infection

  • Based on clinical presentation
  • Risk of infections
  • Objective and subjective evidence
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10
Q
  1. Confirm presence of infection (indication for antibiotics)
    subcategory
A
  1. Confirm presence of infection (indication for antibiotics)
    •Risk factors for infections
    •Subjective evidence
    •Objective evidence
    •What is the (possible) site of infection
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11
Q
  1. Identification of pathogens

subcategory

A
  1. Identification of pathogens
    •What is the (likely) pathogen
    •Any microbiological test sent or results available
    - Extremely impt to obtain cultures before administering antimicrobials

a) Follow-up culture are much less reliable than pretreatment cultures.
•may result in false negative results
•subsequent cultures may not reflect the initial
causative organisms

b) Help decide on need for antimicrobials and narrow down spectrum of therapy
•If results are available, consider
- Contamination, colonizer or true pathogen
- Whether to start or streamline definitive therapy
based on susceptibility test

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12
Q
  1. Selection of antimicrobial and regimen

subcategory

A
  1. Selection of antimicrobial and regimen
    •Empiric, definitive or prophylaxis
    •Consider organism, host and drug factors
    •Decide on choice of agent, route, dosing and duration of treatment
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13
Q
  1. Monitor response

subcategory

A
  1. Monitor response
    •Therapeutic response
    •Adverse drug reactions
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14
Q

Usual sterile sites

A 
CNS 
CVS
Lower respiratory tract
bone/joint
kidney/bladder
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15
Q

Advantage and disadvantage of molecular diagnostic test

A

eg PCR

•Advantages

1) Directly assay for presence of organism
2) Faster results –within hours
3) Detect organisms that don’t grow well on culture media (e.g., M. pneumoniae)
4) Detect organisms that grow very slowly (e.g., M. tuberculosis)

•Disadvantages

1) Not available in all labs
2) More expensive
3) Require skilled personnel
4) May not be true pathogen due to contamination

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16
Q

Antimicrobial susceptibility test methods

A

Agar, broth dilution methods OR disk diffusion method (kirby-bauer disk)
- the lowest [] of an antimicrobial that prevents visible growth of an organism.

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17
Q

Breakpoints

A

Using MIC or Zone of inhibition to predict therapeutic response (BREAKPOINTS)

•Susceptible (S)
- Implies that an infection due to the isolate may be appropriately treated with the dosage of antimicrobial agent recommended for that type of infection and infecting species –likely therapeutic success

•Intermediate (I)

  • It implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physically concentrated or when a high dosage of drug can be used; -uncertain response
  • it also indicates a buffer zone that should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations

•Resistant (R)
- Implies isolates are not inhibited by the usually achievable concentrations of the drug with normal dosage schedules –likely therapeutic failure

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18
Q

Factors that affect abx in-vivo activity (AST)

A
  • Patient’s immune system
  • Protein binding of drug
  • Ability of drug to reach site of infection
  • Drug interactions
  • Some bacteria may only express enzymes that inhibit the antibiotic in vivo
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19
Q

Likely contaminant of blood culture and urine culture

A
  • E.g. likely contaminant from blood culture = Staphylococcus epidermidis(Coagulase negative staphylococcus), bacillus spp.
  • E.g. likely coloniser from urine culture = yeast

IF all 4 tubes(2 sets) have “coloniser” and pt shows sign and symptoms of infection then = true pathogen

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20
Q

use of Antibiogram

A

cumulative susceptibility results
Tabulates antimicrobial susceptibility of common bacterial isolates collected in a hospital / institution

1) assess local susceptibility rates
2) Monitor resistance trends overtime
3) guide selection of tx when culture and susceptibility results are not available (empirical therapy)

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21
Q

empiric
definitive
prophylaxis

A
  • Empiric
  • Microbiological results are not available
  • Antibiotics use is based on clinical presentation of likely site of infection, likely organism causing infection at that site and likely resistant pattern
  • Definitive
  • Also known as culture-directed therapy
  • Antibiotics choice is based on microbiological (ie culture and susceptibility) results
  • Prophylaxis
  • Antibiotics given to prevent an infection eg surgical prophylaxis and post-exposure prophylaxis

prophylaxis ~ 24hrs
open heart surgery ~48hrs

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22
Q

Principles of Antimicrobial Use to Achieve Improved Patient Outcomes

A
  1. Timely initiation of appropriate agents ie most effective, least toxic and the narrowest-spectrum agents required
  2. Administration of dosage individualised to the patient and appropriate to the organism and site of infection
  3. Timely & appropriate alteration in response to clinical responses and microbiological data ie use for the shortest duration possible
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23
Q

selection of antimicrobial agents need to take into account

A

patient
drug
organism factors

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24
Q

take into account Organisms factors

A
  • Identity of the infecting organism
  • Is it fungus, bacteria or virus
  • Which genus and species
  • Susceptibility of the infecting organism
  • If empiric –consider local resistance patterns (antibiogram)
  • If culture-directed –select active antibiotics according to AST

•Combination therapy may be required

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25
Q

Benefits of combination therapy

A

1) Extend spectrum of activity
•Empirical or definitive therapy of polymicrobial infections e.g. piperacillin-tazobactam+ vancomycin for hopsital-acquired pneumonia
•Empirical treatment to cover all resistant strains of the same organism.
E.g. piperacillin-tazobactam+ ciprofloxacin for Pseudomonas aeruginosa

•Achieve synergistic bactericidal effect
•E.g., ampicillin + gentamicin for Enterococcus endocarditis;
Trimethoprim+sulfamethoxazoleagainst various organisms

  • Prevent development of resistance
  • E.g., antimicrobial combinations against M. tuberculosis, HIV
26
Q

Disadvantage of combination therapy

A
  • False sense of security
  • Increased risk of toxicity and allergic reactions •Increased risk of drug interactions
  • Increased cost
  • Selection of multi-drug resistant bacteria
  • Increased risk of superinfections
  • Concern for antagonistic effect (?)
27
Q

Host factors to be taken into account

A
  • History of allergy and ADR
  • Recent antimicrobial use
  • Status of host immune function
  • G6PD deficiency
  • Renal or hepatic impairment
  • Age
  • Pregnancy or lactation
  • Healthcare-associated risk factors
  • Severity of illness
28
Q

Abx generally avoided in children

A

•Antibiotics generally avoided in children –

fluoroquinolones, tetracyclines

29
Q

Hx of allergies and ADR what to do.

A

•History of allergies and ADR
- Difficult to verify and confirm type of reactions

May need to use broader spectrum agent, or more expensive, or less effective

•Cross-reactivity between penicillin:
cephalosporin (<3%) and carbapenem (<1%);

avoid cephalosporin and carbapenem in patient with severe hypersensitivity reactions to penicillins eg immediate IgE-mediated allergic reactions, SJS

30
Q

•Glucose 6-phosphate dehydrogenase deficiency avoid what drug

A

•Avoid sulphonamides, nitrofurantoin

31
Q

Generally safe in pregnancy and lactation DRUGS

A

Generally safe in pregnancy and lactation –
beta-lactams, macrolides

•Generally cautioned or avoided in pregnancy –
co-trimoxazole, fluoroquinolones, tetracyclines

32
Q

Renal or hepatic impairment drug to avoid

A

•Might avoid antimicrobials that can cause further impairment;
nephrotoxicity (e.g. aminoglycosides, vancomycin) or hepatotoxicity (e.g. pyrazinamide, amoxicillin-clavulanate)

33
Q

Status of host immune function DRUGS

A
  • If immunocompromised may be better to use bactericidal drug (e.g. beta-lactams, quinolones, aminoglycosides, vancomycin)
  • If immunocompromised may be more vulnerable to polymicrobial infections, may need combination therapy
34
Q

Severely ill pt drugs

A
  • Severity of illness
  • In severely ill patients, active antibiotics should be initiated as soon as possible

•May need broader spectrum coverage (eg combination for P. aeruginosa)

35
Q

pt who has recent abx use

DRUGS

A
  • Recent antimicrobial use

* If patient failed to get better, may not want to continue with the same antibiotics

36
Q

-Healthcare associated risk factors DRUGS

A
  • Higher risk for multi-drug resistant organisms, eg: •MRSA, Pseudomonas aeruginosa, Acinetobacter baumannii, ESBLproducing gram-negative bacilli
  • If risk factors are present, empiric therapy may need to include broad-spectrum or combination antibiotics
  • Healthcare-associated risk factors include:
  • Antimicrobial use in the last 90 days
  • Residence in nursing home
  • Current hospitalization ≥ 2 days
  • Hospitalization in the last 90 days
  • Chronic dialysis
  • Home infusion therapy
37
Q

-Healthcare associated risk factors example

A
  • Antimicrobial use in the last 90 days
  • Residence in nursing home
  • Current hospitalization ≥ 2 days
  • Hospitalization in the last 90 days
  • Chronic dialysis
  • Home infusion therapy
38
Q

Drugs factor things to note

A
  • Active against suspected organism
  • Ability to reach the site of infection
  • Pharmacokinetics-Pharmacodynamics (PK-PD) characteristics
  • Route of administration
  • Side effect profiles
  • Drug interactions
  • Cost
39
Q

drug MRSA

A

•MRSA: vancomycin, linezolid, daptomycin, ceftaroline •

40
Q

drug pseudomonas aeruginosa

A

Pseudomonas aeruginosa: ceftazidime, cefepime, piperacillintazobactam, ciprofloxacin, levofloxacin, amikacin, gentamicin, aztreonam, meropenem, imipenem

41
Q

drug ESBL enterobacteriaceae

A

•ESBL-producing enterobacteriaceae: meropenem, imipenem, ertapenem

42
Q

drug anaerobic

A

•Anaerobic: clindamycin, metronidazole, amox-clav, piperacillintazobactam, carbapenem

43
Q

•Does not cross blood-brain barrier hence NOT for CNS infections

A

1st and 2ndgeneration cephalosporins, aminoglycosides and macrolides

44
Q

•Used in CNS infections (inflamed meninges):

A

penicillin, ceftriaxone, meropenem, vancomycin

45
Q

drug not used in pneumoia

A

•Daptomycin not for pneumonia as it is inactivated by lung surfactant

46
Q

less effective for abscess

A

Aminoglycosides

47
Q

drug for prostatitis

A

Ciprofloxacin and co-trimoxazole

distribute well to the prostate hence are drug of choice for prostatitis

48
Q

what is •Concentration-dependent bacterial killing

and dosing strategy

A

•Concentration-dependent bacterial killing
•Rate and extent of bacterial killing are a function of the antibiotic concentration
•Higher concentration results in more rapid and more extensive bacterial killing
- Cmax/MIC OR AUC/MIC

•E.g. aminoglycosides, fluoroquinolones

•Dosing strategy
•Optimize Peak:MICratio (peak is 8-10x above MIC) •Usually means larger doses at extended intervals
•E.g. once daily aminoglycoside dosing
•E.g. patient CrCl<30ml/min, PO ciprofloxacin dose recommended is 250mg Q12H or 500mg Q24H,
CHOOSE 500mg Q24hr

49
Q

rational for •Usually means larger doses at extended intervals foraminogycoside

A

Concentrationdependent bacterial killing
Post-antibiotic effect (PAE)
Prevents adaptive resistance –> prevents selection of more resistant mutants
Less nephrotoxicity
Cost

50
Q

Once daily dosing for aminoglycoside

A

for gentamicin and tobramycin at 7mg/KG

  • CrCl >=60 ml/min = q24hr
  • CrCl 40-59 ml/min = q36hr
  • CrCl 20-39 ml/min = q48hr
51
Q

•Time-dependent bacterial killing with no persistant effect (short half-live)

give example and dosing strategy

A
  • Rate and extent of bacterial killing are related to the amount of time the antibiotic concentration is above the MIC of the organism
  • E.g. penicillins, cephalosporins, carbapenems

•Dosing strategies
•Optimize %T > MIC (40-70% of dosing interval above
MIC)
•More frequent dosage administration
•Continuous IV infusion or prolonged intermittent
infusion (to get higher trough [])
•Block excretion (probenecid)

52
Q

•Time-dependent bacterial killing with persistant effect (long half-live or post-antibiotic effect)

give example and dosing strategy

A
  • Rate and extent of bacterial killing are related to the overall drug exposure (AUC) vs MIC
  • E.g., vancomycin

•Dosing strategy
•Optimize AUC:MIC ratio
(e.g. for vancomycin -target of 400 for MRSA)

•Dependent on total daily dose
vancomycin dont give more than 2g as single dose
3g/day VS 1.5g q12hr
= choose 1.5g q12hr
because 3g/day will have higher peak –> more SE
even though AUC will be the same coz CL is same in the same pt.

53
Q

when to use IV

A

for hospitalised, severe infections, when high blood concentration is required

  • Oral route is preferred unless:
  • Absorption problem (e.g., Gl pathology)
  • Suitable oral antibiotic not available
  • High tissue concentrations essential e.g., endocarditis, meningitis, bone/joint
  • Urgent treatment required
  • Patient non-compliance
54
Q

drugs with good bioavailability

A

FQ, metronidazole, linezolid, co-trimoxazole

55
Q

CYP450 inhibitor

A

azole antifungal and macrolide except azithromycin

56
Q

CYP 450 inducer

A

rifampicin

57
Q 
Duration of tx 
surgical prophylaxis
chlamydia cervicitis 
UTI
Respiratory 
skin
Endocarditis 
osteomyelitis 
TB 
chronic suppression 
HIV
A

single dose or 24hr
surgical prophylaxis
chlamydia cervicitis

5-14days
UTI
Respiratory
skin

4-6weeks
Endocarditis
osteomyelitis

months
TB
chronic suppression

lifelong
HIV

58
Q

Monitor response factors

A

1) Treatment Goals
•Achieve therapeutic response
•Lack of adverse drug reactions

2) Therapeutic response
•Resolution of symptoms and signs (subjective and
objective)
•Microbiological clearance –eradication of organism
•Absence of complications/ progression

3) Adverse drug reactions
•E.g. All new antibiotics –rashes, itch, angioedema aminoglycoside –serum creatinine, urine output; vancomycin –flushing, hypotension, itch

59
Q

Modify therapy?

A

•When susceptibility/microbiologic tests become available
- Optimise therapy: escalate or de-escalate

•Satisfactory response
- Convert IV to Oral
- De-escalate / streamline ie broad spectrum to
narrower spectrum antibiotics
- Stop if completed adequate duration

•Unsatisfactory response

60
Q

causes of unsatisfactory response

A

•Inappropriate diagnosis

 - Non infectious causes 
 - Non-bacterial infections

•Inappropriate choice of agent

 - Resistance 
 - Development of resistance

•Subtherapeutic concentration

  - Non-compliance 
  - Improving renal function 
  - Drug interactions
  • Collections or abscess –needs surgery or drainage •Impaired host defense
  • Superinfection
  • Toxicity of the drug

Antibiotic (21 decks)

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