Exam 1: Intro to Antibiotics Flashcards
General Approach
Antimicrobial Targets
Chemical Classes
- Beta-lactams
- Aminoglycosides
- Tetracyclines
- Etc
Pharmacological Classes
- Cell wall synthesis inhibitors
- Proteins synthesis inhibitors
- Etc
Activity Classes
- Gram +
- Gram -
- Aerobic
- Anaerobic
Spectrum Classes
Narrow vs Broad
Spectrum
- Broad spectrum
- Likely to kill pathogen
- Also likely to kill good microbes
- Narrow spectrum
- Lower chance of killing pathogen
- Fewer adverse effects
Spectrum
Considerations
1 pathogen can cause different diseases:
Severity of illness matters.
De-escalation
Start Broad, Narrow Down
- Give “best chance” abx empirically
- Multiple abx may be required
- Encouraged by institutional guidelines
- Encourages broad-spectrum abx use
- Spectrum is not the only variable
Selective Toxicity
Many abx work on pathways in bacteria that are similar but different than those in humans.
-
Differences in biochemistry
- Methotrexate ⇒ ⊗ dihydrofolate reductase in most organisms
- Not selective ⇒ more severe/common adverse effects
- Trimethoprim ⇒ ⊗ dihydrofolate reductase in bacteria
- Methotrexate ⇒ ⊗ dihydrofolate reductase in most organisms
-
Drug accumulation
- Tetracycline ⇒ ⊗ 30S ribosome
- Permeates bacterial membranes better than human membanes
- Dose required to inhibit bacteria much lower than for humans
- Tetracycline ⇒ ⊗ 30S ribosome
-
Cytology differences
- Cell-wall synthesis inhibitors
- Binds to target human cells lack
Empiric Therapy
Selected before causative organism known.
Factors involved:
-
Likely pathogens
- Which types cause suspected infection?
-
Drug activity
- Which abx active against likely pathogens?
-
Pharmacokinetics
- Which abx most active @ site of infection?
-
Patient factors
- Adverse effects?
- Patient vulnerable to atypical pathogens?
-
Cost
- Which abx most economically feasible for patient and healthcare system?
Definitive Therapy
Selected once causative organism and susceptibility known.
Similar factors should be considered.
Therapy narrowed to avoid over-treating.
Abx Pharmacokinetics
Dictates utility of abx for various diseases in various settings:
-
Absorption
- PO?
- Too much or too little for success?
-
Distribution
- Concentrate at site of infection?
- Tissue penetration?
- Patient factors?
-
Metabolism
- Is drug metabolized?
- Where, hepatic vs extra-hepatic?
- Drug interactions?
-
Elimination
- How is abx removed?
- Renal dysfunciton or nephrotoxicity?
- Extracorporeal elimination?
Tissue Penetration
- Generally good
- Urine, kidneys, soft tissues
- Generally poor
- Prostate, eye, abscess, vegetation
- CNS
- Variable
- Often dependent on inflammation
Patient Factors
Drug delivery can be influenced by:
- DM
- Peripheral vascular disease
- Ascites
- Burns
Abx Pharmacodynamics
Bacteriostatic vs Bactericidal
- Different types of activity for different organisms
- Combo of static drugs may be cidal
- In vitro vs in vivo effects
- Activity based on normal achievable concentrations in humans
Concentration-dependent
Drugs
- Level of activity dependent on Peak:MIC ratio or AUC:MIC ratio
- e.g. how high above a therapeutic dose
- Higher concentrations kill better
- Ideal admin ⇒ infrequent, high doses
- Ex:
- Metronidazole
- Aminoglycosides
- Fluoroquinolones
- Daptomycin
Time-dependent
Drugs
“Concentration-independent drugs”
- Level of activity dependent on time above MIC
- Constant levels are ideal
- Levels much higher than MIC do not result in better killing
- Ideal admin ⇒ continuous infusion or frequent, smaller doses
- Ex:
- Beta-lactams
- Vancomycin
- Macrolides
- Tetracyclines
