Principles of antimicrobial use Flashcards
What is an infection?
organism/pathogen invades host tissues and elicit inflammatory/immune host responses
What is sepsis?
life-threatening organ dysfn caused by dysregulated host response to infection
What are the 4 things in a systemic approach to antimicrobial use?
- Confirm presence of infection
- Identify likely pathogens
- Select antimicrobial agents and regimen
- Monitor response
Which 2 steps fall under indication for Abx?
- Confirm presence of infection
2. Identification of (likely) pathogens
Which step falls under the ‘regimen (choice, route, dose, duration)’
Step 3: Selection of antimicrobial and regimen
Which step falls under the ‘monitoring and plan’?
Step 4: Monitor response
How to confirm presence of infection?
a. Any risk factors for infection
b. subjective evidence
c. objective evidence
d. Possible site of infection
- looking for diagnosis
What are 4 risk factors to look at for infection?
- Disruption of natural protective barriers (innate immunity)
- Age
- Immunosuppression
- Alterations in normal flora of the host with conditions that promotes overgrowth of MO
What to look at for subjective evidence?
- Localised symptoms (diarrhoea, N/V, dysuria, pain, purulent discharge)
- Systemic symptoms (feverish, SOB, weakness/tiredness, etc.)
What to look at for objective evidence?
- Vital signs (Fever, Hypotension, Tachypnoea, HR, Mental status)
- Lab test (non-specific biomarkers, acute-phase reactants)
- Radiological imaging
CONSIDER TREND; baseline VS current values
Guidelines for starting of ABx: When procalcitonin levels are?
> = 0.5 ug/L: ABx encouraged
Guidelines for continuing of ABx: When procalcitonin levels are?
decrease by 80% from peak concentration; and >= 0.5 ug/L: Continue Abx
Guidelines for stopping of ABx: When procalcitonin levels are?
< 0.5 ug/L: Stop Abx
How do we find the possible site of infection?
- Clinical presentation
- Risk of infections
- O and S evidence
- Common sites are UTI, Resp tract, soft tissues, intra-abdominal
What is considered a pathogen?
Organisms capable of damaging host tissue and eliciting a host response and signs and sx of an infection
What is a coloniser? Example?
Presence of normal flora/pathogenic organisms without eliciting a host response
e.g. yeast from urine culture
What is a contaminant?
Example?
Presence of MO typically acquired during collection/processing of host specimens w/o evidence of host response
e.g. S. epidermidis (from skin) + bacillus spp.
What is empiric therapy? and when to use empiric therapy?
- When micrological results are unavailable
- Clinical presentation of likely site of infection
- Likely susceptibility
- Antibiogram
What is definitive therapy? and when to use definitive therapy?
- Culture-directed therapy
- based on pts specific microbiological (culture and susceptibility tests)
What is prophylaxis therapy? and when to use prophylaxis therapy?
- Abx given to prevent infection
e. g. surgical prophylaxis; post-exposure prophylaxis
Benefits of combination therapy?
- Extend spectrum of activity
e. g. pip-tazo + vancomycin (covers MRSA) for HA-pneumonia
e. g. pip-tazo + ciprofloxacin (to broaden; cover p.aeruginosa) for VA-pneumonia - Achieve synergistic bactericidal effect (however, note that indifference/antagonism happens too)
e. g ampicillin + gentamicin or amipicllin + ceftriaxone for enterococcus endocarditis - Prevent development of resistance
e. g. TB treatment
Limitations of combination therapy?
- Inc toxicity and allergic rxns
- Inc risk of DDI
- Inc cost
- Selection of MDR bacteria
- Inc risk of superinfections
- Concern for antagonistic effect (VS synergisitc)
What are some host factors to consider when choosing the ABx?
- Age
- G6PD def
- History of allergies and ADR
- Cross-reactivity btw penicillins and other b-lactams
- Preg/lactation
- Renal/hepatic impairment
- Status of host immune fn (use bactericidal drugs for immunocompromised + combination therapy as more vulnerable to polymicrobial infection)
- Severity of illness
(may need broader spectrum e.g. covering Pseudomonas) - Recent Abx use
What are some drug properties to consider when choosing the ABx?
- Active against suspected organism
- Ability to reach site of infection (CNS penetration)
- PK-PD
- ROA
- Side effects
- DDI
- Cost
Enterobacteriacea VS Enterobacterales
Family VS Order
Different route of administrations
IV, IM, PO, intrathecal, inhalation, topical
When is IV route used?
hospitalised, severe infections, when high blood conc is required
Why is oral the preferred route?
IV needle can also cause infection; for the comfort of the patient
Less invasive and less nursing time
Oral prevents irritation to vein/ occur blood stream infections
When is oral route not used?
- Absorption problem (GI pathology)
- Suitable oral ABx unavailable
- High tissue conc essential (e.g. meningitis, endocarditis, bone/joint)
- Urgent treatment required
- Patient non-compliance
ABx example with good oral F
- FQs
- metronidazole
- linezolid
- co-trimoxazole
Advantages of using IV ROA?
- higher ABx conc, more reliable levels, for pts unable to abs orally (100% F)
Disadvantages of using IV ROA?
- Need IV access
- Hospital administration
- Phlebitis
- Cost
Why is IM less commonly used?
Painful
Only for community based
e.g. Streptomycin, Ceftriaxone, Benzathine penicillin
When is aerosolised/nebulised used?
Nebulised colistin for MDR resistant P. aeruginosa pneumonia
What are some drug side effects/ADR we need to consider?
- cdad
- collateral damage
Ecological adv effects when selecting organism and colonisation of MDR
Not only with the Abx but also other Abx
What are some DDI PK-PD we need to consider?
- CYP450 inhibitors (e.g. azole antifungals, macrolides)
- CYP450 inducers (e.g. rifampicin)
- Carbapenems and valproate NOT USED TOGETHER
- cross-reactivity with penicillins with other b-lactams
The cost of drug includes:
acquisition, preparation, administration, monitoring
What is a treatment goal?
- When you achieve therapeutic response
- Lack of ADR
What is a therapeutic response?
- Resolutions of S&S (the subjective and objective should be resolved)
- Microbiological clearance - eradication of organism
- Absence of complications/progression
What are some ADR that occurs in new ABx?
Rashes, itch, angioedema
When do we modify therapy?
- When susceptibility/microbiologic tests becomes available (optimise therapy: escalate or de-escalate)
- Satisfactory response (Convert IV to Oral; De-escalate/streamline from broader to narrower spectrum Abx; Stop if completed adequate duration)
- Unsatisfactory response
What are the causes of unsatisfactory response?
- Inappropriate diagnosis (could be fungal/viral)
- Inappropriate choice of agent (resistance develop)
- Subtherapeutic conc (non-compliance, improving renal fn, DDI)
- Collections or abscess - needs surgery or drainage
- Impaired host defense
- Superinfection
- Toxicity of the drug
How long to wait to evaluate clinical response?
48-72hours
what Abx we avoid in children
FQs (anthropathy), tetracyclines (discolor teeth)
what Abx to avoid in G6PD deficiency
sulfonamides (co-ts), Nitrofurantoin, ?FQs
which B lactam doesnt have any cross reactivity with the other B lactams
cefazolin
what are some examples of possible cross reactivity of B lactams?
- amoxicillin and ampicillin
- amoxicillin/ampicillin with cephalexin
- cefepime and ceftriaxone
- ceftazidime and aztreonam
which abx are safe in preg
B lactams, macrolides
abx to avoid in preg
FQs, Co-TS, tetracycline
what abx cause nephrotoxicity
AGs, high dose vancomycin
what abx cause hepatotoxicity
pyrazinamide, augmentin
what are bactericidal abx
B lactams, quinolones, AGs, vancomycin
abx to treat CNS infections
penicillin, ceftriaxone, cefepime, ceftazidime, meropenem, vancomycin
abx that dont concentrate in CSF
1 and 2 cephalosporins, AGs, macrolides, clindamycin
abx covering ESBL producing enterobacterales
4th gen cephalosporins, carbapenems
abx covering Amp-C producing enterobacterales
4th gen cephalosporins, carbapenems
abx covering anaerobic
augmentin, carbapenem, pip-tazo, metronidazole
abx which are concentration-dependent kill
AGs, FQs
what is concentration-dependent bactericidal killing
- higher conc results in more rapid and more extensive killing
- optimise peak: MIC ratio (where the peak is 8-10x above MIC)
- ciprofloxacin 500mg Q24H better than 250mg Q12H
rationale behind once-daily dosing of AGs (for conc-dependent killing)
- post-abx effect
- prevents adaptive resistance –> prevents selection of more resistant mutants
- less nephrotoxicity
- lower cost
how do we change dose interval for conc-dependent killing?
hartford nomogram
CrCL:
>= 60 -> 24H
40-59 -> 36H
20-39 -> 48H
or based on graph concentration: <7.5 = Q24H 7.5-11 = Q36H >11 = Q48H
what is the abx that falls under time-dependent bacterial killing with no persistent effect (short half live)
B lactams (pen, cephalosporins, carbapenems)
what is time-dependent bacterial killing with no persistent effect (short half live)
amt of time the abx conc is above the MIC of organism
dosing strategies for
time-dependent bacterial killing with no persistent effect (short half live)
-%time > MIC (40-70% dosing interval above MIC)
- more freq dosage administration
- continuous IV infusion or prolonged intermittent infusion
- block excretion by giving probenecid
what abx fall under time-dependent bacterial killing with persistent effect (long half live or post-abx effect)
vancomycin
what is time-dependent bacterial killing with persistent effect (long half live or post-abx effect)
rate and extent of bacterial killing related to AUC vs MIC
what is the dosing strategy for time-dependent bacterial killing with persistent effect (long half live or post-abx effect)
optimise AUC: MIC ratio (vancomycin: target 400-600 for MRSA)
- dependent on TOTAL DAILY DOSE
e. g. 500mg Q12H or 1g Q24H –> we give the 1g q24h as IV injection given once
ADR in AGs and vancomycin
AGs: serum creatinine, urine output
vancomycin: flushing, hypotension, itch
what to take note about daptomycin
not used in pneumonia as daptomycin is inactivated by lung surfactant
what to take note with AGs
less effective in abscesses
which gram -ve bacteria can produce Amp-C beta-lactamase?
- Enterobacter
- Citrobacter freundii
- Providencia
- Proteus vulgaris
- Morganella
- Serratia
these may develop resistance against 3rd gen cep
what are 2 examples of superinfections?
Second infection superimposed of the first infection:
1) Clostridioides Difficle (cause kill the susceptible microbes alr
(2) Fungal infections
