Principles of Antimicrobial Use Flashcards
What are the 4 key steps in the systematic approach to antimicrobial use?
- Confirm presence of infection [INDICATION]
- Identification of pathogens [INDICATION]
- Selection of antimicrobial and regimen [REGIMEN]
- Monitor response [MONITORING]
Step 1: Confirm presence of infection
What are the parameters to consider?
- 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
- Subjective (symptoms): localized and systemic
- 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
- Site of infection
Step 1: Confirm presence of infection
Why is procalcitonin more useful than CRP?
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
Step 1: Confirm presence of infection
When is a second PCT conc. obtain? (1st one obtain in early stage of episode)
6-12h later
Step 1: Confirm presence of infection
Other than bacteria infection, Procalcitonin may also be elevated in:
- ESRF (since it is cleared by the kidneys)
- Traumatic brain injury (TBI)
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?
Follow up cultures may not reflect initial causative organisms
Follow up cultures can cause false negative
Step 2: Identification of pathogens, indication for antibiotic
What is the difference between pathogen, coloniser, and contaminant?
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)
Step 2: Identification of pathogens, indication for antibiotic
Mixed growth is often due to ________
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
Step 2: Identification of pathogens, indication for antibiotic
What are some considerations to determine if its a pathogen?
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
Step 3: Selection of antimicrobial regimen
What to consider?
- Empiric, definitive (culture-directed), or prophylaxis
- Which agent, route, dosing, duration
- Consider organism, host, drug factors
Step 3: Selection of antimicrobial regimen
Empiric therapy is based on ______, while definitive therapy is based on ________
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)
Step 3: Selection of antimicrobial regimen
What are some organism factors?
- Identify organism
- Susceptibility/resistance of the infecting organism
- Assess need for combination therapy
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.
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
Step 3: Selection of antimicrobial regimen
When might we consider using combination therapy (advantages)?
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)
Step 3: Selection of antimicrobial regimen
What are some disadvantages of combination therapy?
- 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)
