What is empiric therapy?
- antimicrobial therapy targeting likely pathogens
- need to consider clinical presentation, patient risk factors, and pharmacokinetic factors
How do we assess clinical presentation for empiric therapy?
- probable site of infection (lungs skin, blood)
- suspected organism based on disease state
What aspects of a patient history should be considered when determining risk factors?
- demographics
- past infection/colonization
- contacts; people and animals
- co-morbid conditions
- antimicrobial use
- prior hospitalizations
- travel/new Canadian
What pharmacokinetic factors should be considered for empiric therapy?
- Absorption: N/V, diarrhea, intact bowel
- Distribution: suspected site of infection, underweight or obese
- Metabolism: known enzyme deficiency
- Excretion: hepatic or renal impairment
Cultures collected ____ starting antimicrobial therapy are most useful because…
- before
- collecting samples after even one dose of antibiotics can reduce likelihood of isolating pathogen
- two blood culture sets from two separate sites if suspected bacteremia
What drug considerations are made for empiric therapy?
- spectrum
- mechanism of action
- pharmacokinetics and pharmacodynamics
What are pharmacokinetics and pharmacodynamics?
Pharmacokinetics: what the body does to the drug, ADME
Pharmacodynamics: how the drug acts on the body, influenced by spectrum, mechanism of action, and site of infection
What is broad spectrum vs narrow spectrum antimicrobials?
Broad spectrum: effective against many different types of pathogens, good for empiric therapy
Narrow spectrum: effective only against a few types of pathogens, good for targeted therapy
What is bactericidal vs. bacteriostatic?
Bactericidal: causes microbial death, required in serious infections
Bacteriostatic: inhibits microbial growth, requires a functioning immune system, used for less serious infections
What is concentration-dependent killing?
- need a required concentration to minimum inhibitory concentration (MIC) ratio
- targeting a specific concentration
- dosed less frequently, often once per day
What is time-dependent killing?
- longer time above minimum inhibitory concentration (MIC)
- targeting a length of time above MIC
- generally dosed multiple times a day
What are three ways that antimicrobials can be combined to improve empiric therapy?
1) Broaden spectrum of activity; can help to fill in the gaps in one drug’s spectrum
ex. adding metronidazole to a cephalosporin
2) Double coverage; two antimicrobials covering a similar spectrum
ex. Pseudomonas infection may be treated with a beta-lactam and aminoglycoside
3) Synergism; two antimicrobials provide a stronger effect together than on their own
ex. beta-lactam and aminoglycoside
How does the site of infection help to determine appropriate empiric therapy?
Helps to determine which antimicrobials are most appropriate based on:
- common causative pathogens
- localized or disseminated nature
- “hard to reach” area such as brain, bone or biofilm
How does potential antimicrobial resistance help to determine appropriate empiric therapy?
The ability of certain microbes to develop tolerance to specific antimicrobials to which they were once susceptible; broad spectrum empiric therapy is optimal
What increases risk of resistance?
- recent antibiotic use (3 months)
- previous hospital admissions or from long term care
- travel history and new Canadians
What are four mechanisms of resistance used by microbes?
1) Enzymes that deactivate the drug (ex. beta lactamase)
2) Alteration of drug binding target protein (ex. MRSA has altered penicillin binding protein)
3) Alteration of the structure or electrical charge of the membrane (ex. aminoglycoside resistance)
4) Efflux pumps to remove drug from the cell (ex. some gram negatives)
What is efficacy?
- improvement of presenting signs and symptoms
- can take 2-5 days depending on severity of infection
- important to inform team if patient is not improving
What adverse effects should be monitored for?
- nausea, vomiting, diarrhea, headache, rash
- allergic reaction: hives, SOB
How do we monitor for therapeutic drug levels?
- timing of drawing the level is key
- trough level: lowest serum concentration, draw 30 min BEFORE antibiotic dose is given
- peak level: highest serum concentration, draw AFTER antibiotic dose finishes infusing
- important for vancomycin and aminoglycosides
What targeted therapy?
- antimicrobial therapy targeting known pathogens
- reduces risk of resistance, C. difficile infections, and opportunistic infections
- if pathogen not identified, broad spectrum therapy is continued for the entire duration
What is prophylaxis therapy?
- antimicrobial agent given to prevent an infection
- given after exposure to certain pathogens (ex. N. meningitidis)
- given for immunocompromised patients (HIV, cancer, etc.)
What are 6 types of antibiotic targets?
1) Cell wall synthesis
2) Cell membrane
3) Folate synthesis
4) DNA
5) Protein synthesis
6) Multiple targets
Why do antibiotics target cell wall synthesis?
- selective toxicity toward bacterial cells (prokaryotic)
- preventing proper cell wall formation leads to weak cell walls
- cell unable to withstand osmotic pressure
- cell ruptures and dies
What is the mechanism of action of beta lactams?
- peptidoglycan is the major component of bacterial cell walls
- transpeptidation requires penicillin binding protein (PBP)
- beta lactams bind to active site of PBPs, inhibiting peptidoglycan synthesis and thus cell wall formation
- leads to cell rupture
- bactericidal to growing cells; time-dependent killing
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Structure, Reproduction & Classification67
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Microbiology of Pathogenic Factors45
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Respiratory Tract Infections58
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Central Nervous System Infections55
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Specimen Collection & Laboratory Diagnosis76
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Infection Prevention & Control47
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Cardiovascular System Infections40
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Gastrointestinal System Infections59
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Skin and Soft Tissue Infections56
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Sexually Transmitted Infections76
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Antimicrobials39
