EXAM #4: INTRODUCTION TO ANTIBACTERIAL AGENTS Flashcards
What shape are streptococci?
Chains
What shape are staphylococci?
Grape-like clusters
What shape are pleomorphic bacteria?
Many-shapes
What molecule is the foundation of the bacterial cell wall?
Peptidoglycan
What is peptidoglycan?
Macromolecule of:
- Peptides
- Sugars
In regards to peptidoglycan, what is the difference between gram positive and gram negative bacteria?
Gram positive= thick wall of peptidoglycan
Gram negative= thin wall of peptidoglycan
- PLUS an OUTER MEMBRANE
What is LPS?
Lipopolysaccharide
What is lipopolysaccharide?
Macromolecule of:
- Phospholipids
- Polysaccharides
What type of bacteria is LPS associated with?
Gram negative
What is the effect of LPS from a therapeutic standpoint?
Prevents penetration of the organism by bulky/ high molecular weight drugs
E.g. erythromycin
What effect does the lipid bilayer in Gram negative bacteria from a therapeutic standpoint?
Prevents penetration by water-soluble drugs
What is the effect of hydrophillic pores in Gram negative bacteria?
Allows penetration by water soluble drugs
E.g. sulfonamides
What is the role of nutrient receptors in Gram negative therapy?
Nutrient receptors can be utilized by structurally similar drugs to gain entry into the organism
What type of bacteria is Teichoic acid associated with?
Gram positive
What effect does Tiechoic acid have on therapy?
- Anionic
- Can hinder penetration of drugs with a negative charge
What effect does the lipid bilayer have on therapy in Gram positive bacteria?
Limits the penetration of water soluble drugs
E.g. sulfonamides
What is the definition of selective toxicity?
Therapy aimed at killing only the target organism
- Uses drug targets that are specific to organism
What are the common strategies for killing or inhibiting microorganism growth?
1) Disrupt the coding/ genetic machinery
2) Block protein synthesis
3) Disrupt cell wall/ membrane synthesis
What is the definition of bactericidal?
Agent will KILL the bacteria
What is the definition of bacteriostatic?
Agent will INHIBIT GROWTH of the bacteria
Note that this type of elimination is DEPENDENT on host immune system
What is a narrow spectrum abx?
Drug that is TARGETED to a specific species of bacteria
What is a broad spectrum abx? When would you employ broad spectrum therapy?
Drug that has an effect on a variety of organisms
Use if the causative agent is unknown
What is prophylactic therapy?
- Treatment without disease
- Prevention
What is pre-emptive therapy?
- Treatment of a high-risk patient that is infected
- but, ASYMPTOMATIC
What is empirical therapy?
Treatment of a SYMPTOMATIC patient without testing/confirmation of the causative organism
What is definitive therapy?
Treatment once the causative organism has been identified
What is suppressive therapy?
- Low dose therapy used as a “secondary prophylaxis”
- Causative agent is likely still present
What is the definition of resistance?
When the agent is no longer effective, OR is less effective against the organism
How do bacteria develop drug resistance?
1) Acquisition of NEW genetic material
2) Mutation in the EXISTING genome
What mnemonic can be used to remember the “nosocominal superbugs?”
ESKAPE
- Enterococcus faecium
- Staphylococcus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanni
- Pseudomonas aeruginosa
- Enterobacter species
What resistance mechanism is associated with Daptomycin?
- Gene mutation (mprF) that changes the CHARGE of the bacterial membrane
- Positive
- Repels positively charged abx i.e. Daptomycin
Generally, this is an example of REDUCED DRUG ENTRY
What resistance mechanism of associated with Tetracycline?
- Expression of an EFFLUX PUMP that pumps Tetracycline OUT of the organism
- This is an example of increased DRUG EFFLUX*
What resistance mechanism is associated with Metronidazole?
- Metronidazole is a pro-drug
- Must be REDUCED to be ACTIVE
- Bacteria develop mutations that alter the enzymes that activate Metronidazole
Example of changes in enzymes that activate the drug
What resistance mechanism is associated with Aminoglycosides?
- Mutations produce enzymes that chemically modify the drug
- Structural changes impair binding to target
Imparied drug binding to targets
What resistance mechanism is assocaited with Amoxicillin?
- Expression of Beta-lactamase
- Enzyme hydrolyzes the lactam ring that is part of the amoxicillin structure
What is the trade name of Amoxacillin + a Beta-Lactamase inhibitor?
Augmentin
What is the resistance mechanism that is associated with TMP-SMX?
- Mutation of the drug binding site
E.g. TMP-SMX targets dihydrofolate reductase–drug binding site is altered but the enzyme still functions
What is the mechanism of Vancomycin resistance?
- Vancomycin inhibits cell wall synthesis
- Binds to sites in the growing peptidoglycan wall and sterically inhibits the synthesis of peptidoglycan
- Mutation prevents vanocmycin binding but still allows the formation of the cell wall
