Principles of Antimicrobial Use Flashcards
What does “antimicrobial stewardship” means?
Careful & responsible management of antimicrobials through the use of a systematic approach.
List the steps of the systematic approach to antimicrobial use.
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
What are some host factors that increase the risk of infection in an individual?
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
What are some localised subjective symptoms observed in patients with ongoing infections?
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)
What are some systemic subjective symptoms observed in patients with ongoing infections?
1) Fever, chills & rigours
2) Malaise / general tiredness
3) Palpitations
4) Shortness of breath
5) Mental status changes
6) Weakness
List some objective parameters used to help with the confirmation of a likely infection in an individual.
1) Vital signs
2) Laboratory test
3) Radiological imaging
What are some vital signs observed in an individual who is likely undergoing an infection?
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
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?
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
Do inflammatory laboratory markers suffice as infection laboratory markers?
No
List the laboratory biomarkers used to indicate an infection in an individual.
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)
At what concentration of procalcitonin should the use of antibiotics be encouraged in patients with ongoing infections?
> = 0.5 mcg/L
What are the conditions in which antibiotics should be discontinued in patients who had infections?
1) [procalcitonin] < 0.5 mcg/L
OR
2) Decrease by 80% from peak concentration
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?
No. Continuation of Abx is encouraged when [procalcitonin] >= 0.5 mcg/L AND decrease in peak concentration < 80%.
Under what conditions should a change in Abx be considered in a patient suffering from an infection?
1) Increased [procalcitonin] compared to peak concentration
AND
2) [procalcitonin] >= 0.5 mcg/L
For a patient with chronic kidney disease who display signs of an infection, what should be considered when determining the need to initiate antibiotics?
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.
What should we look for when using radiological imaging to determine if a patient is currently infected?
Tissue changes, collections, abscesses & obstructions.
Why is it extremely important to obtain cultures before administering antimicrobials?
- 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
Differentiate between pathogens, colonisers & contaminants.
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
Name a likely contaminant from blood culture.
1) Staphylococcus epidermidis
2) Bacillus spp.
Name a likely coloniser from urine culture.
Yeast
Explain the differences between empiric, definitive & prophylaxis antimicrobial therapy.
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)
What are the principles of antimicrobial use to achieve improved patient outcomes?
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
What are the factors affecting the selection of antimicrobial agents to treat infections?
1) Host (patient) factors
2) Organism factors
3) Drug factors
Discuss the organism factors affecting the selection of antimicrobial agents.
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
What are the advantages of using combination Abx therapy?
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
What are the disadvantages of using combination Abx therapy?
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)
Discuss the host factors affecting the selection of antimicrobial agents.
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
Which classes of antibiotics are generally avoided in children?
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
Which classes of antibiotics are generally avoided in patients with G6PD deficiency?
1) Sulphonamides (e.g. sulfamethoxazole & cotrimoxazole)
2) Nitrofurantoin
Is the cross-sensitivity between penicillins & other beta-lactams attributed as a class effect that results in allergic reactions?
No. Cross-sensitivity is a result of the presence of similar side chains in the chemical structures of certain beta-lactams.
Name three clinically relevant cross-reactivity reactions displayed by beta-lactams.
1) Penicillins G & V
2) Amoxicillin & ampicillin
3) Ampicillin & cephalexin
4) Cefepime & ceftriaxone
5) Ceftazidime & aztreonam
Which beta-lactam(s) do(es) not display cross-reactivity with other beta-lactams?
Cefazolin
Which classes of antibiotics are generally cautioned or avoided in pregnancy or lactation?
1) Tetracyclines
2) Fluoroquinolones
3) Cotrimoxazole (esp. first & last trimesters)
4) Nitrofurantoin (at term > 38 weeks)
Which classes of antibiotics are generally safe in pregnancy and lactation?
Beta-lactams & macrolides
Name two antimicrobials that are generally cautioned or avoided in patients with impaired renal functions?
1) Aminoglycosides
2) High-dose vancomycin
3) Amphotericin B
Name two antimicrobials that are generally cautioned or avoided in patients with impaired hepatic functions?
1) Amoxicillin-clavulanate
2) Tetracyclines (tetracycline, doxycycline & minocycline)
3) Macrolides (erythromycin, clarithromycin & azithromycin)
4) 5-flucytosine
5) Triazoles (fluconazole, itraconazole & voriconazole)
6) Pyrazinamide
Which classes of antibiotics are generally used in immunocompromised patients with infections?
Bactericidal:
1) Beta-lactams
2) Vancomycin
3) Aminoglycosides
4) Fluoroquinolones
Which classes of antibiotics are recommended to treat MSSA infections?
1) Pencillinase-resistant penicillins (cloxacillin)
2) 1st gen cephalosporins (cefazolin & cephalexin)
Which antibiotic(s) is/are recommended to treat MRSA infections?
Recommended: Vancomycin
Alternatives: Ceftaroline, tigecycline & linezolid
Which classes of antibiotics are recommended to treat infections caused by Pseudomonas aeruginosa?
1) Anti-pseudomonal penicillins (piperacillin-tazobactam)
2) 3rd & 4th gen cephalosporins (ceftazidime & cefepime)
3) Carbapenems (imipenem-cilastatin & meropenem)
Which classes of antibiotics are recommended to treat infections caused by ESBL-producing enterobacterales?
Carbapenems
Which classes of antibiotics are generally avoided when treating infections caused by Enterobacter species? Why so?
3rd generation cephalosporins (ceftriaxone & ceftazidime)
- may produce Amp-C beta-lactamases on exposure, leading to cephalosporin resistance
- cefepime may retain activity
Which antibiotic(s) is/are recommended to treat Bacteriodes fragilis infections?
Recommended: Metronidazole
Alternatives: Amoxicillin-clavulanate, piperacillin-tazobactam, carbapenems
Which antibiotic(s) is/are recommended to treat Clostridiodes difficiles infections?
1) PO metronidazole (mild)
2) PO vancomycin (mild, moderate & severe)
Which classes of antibiotics are recommended to treat CNS infections?
1) Pencillins
2) 3rd & 4th gen cephalosporins: ceftazidime, ceftriaxone & cefepime
3) Meropenem
4) Vancomycin (primarily for gram +ve infections)
Which classes of antibiotics should NOT be used for CNS infections?
1) 1st & 2nd gen cephalosporins
2) Aminoglycosides
3) Macrolides
4) Clindamycin
Which antibiotic is not used for pneumonia?
Daptomycin (inactivated by lung surfactant)
Which antibiotics are drugs of choice for prostatitis?
Cotrimoxazole & ciprofloxacin
List the classifications of antibiotics available based on their PK-PD characteristics. Name the parameter used in the classification of each category.
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)
What does ‘post-antibiotic effect’ (PAE) refer to?
PAE is the ability of an antimicrobial agent to persistently suppress bacterial growth even at low or undetectable concentrations.
Name a class of antibiotics that exhibits concentration-dependent bactericidal killing properties.
1) Aminoglycosides
2) Fluoroquinolones
Name a class of antibiotics that exhibits time-dependent bactericidal killing properties with no persistent effect.
Beta-lactams (except ertapenem & ceftriaxone)
Name a class of antibiotics that exhibits time-dependent bactericidal killing properties with persistent effects.
Vancomycin
What is the dosing strategy for Abx exhibiting concentration-dependent bactericidal killing properties? Why so?
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.
What is the dosing strategy for Abx exhibiting time-dependent bactericidal killing properties with no persistent effect?
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
What is the dosing strategy for Abx exhibiting time-dependent bactericidal killing properties with persistent effects?
Optimise AUC / MIC ratio
- Dependent on total daily dose
- E.g. for vancomycin: target AUC / MIC ratio = 400-600
Under what conditions are oral administration not recommended?
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
What does ‘collateral damage’ refer to?
Refers to the increased risk of microorganisms developing Abx resistance against other Abx outside of currently used Abx.
Which antibiotic is known to be a CYP450 inducer?
Rifampicin
Which classes of antimicrobials are known to be inhibitors of CYP450 enzymes?
1) Macrolides
2) Triazoles
What are some possible reasons for an unsatisfactory response to antimicrobial therapy?
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
