AST Part 2: Antimicrobials Flashcards
What are ways that antimicrobials act on microorganisms by inhibiting?
Antimicrobials act on microorganisms by inhibiting:
- Cell Wall Synthesis
- Cell Membrane Function
- Protein synthesis
- Nucleic acid synthesis
- Metabolic Processes
What are beta-lactams? What agents does it include?
Beta-Lactams:
These are antimicrobials that have a beta-lactam ring in common. They are bactericidal, broad spectrum, generally non-toxic, efficacy varies (different PBP’s, etc.)
It includes lots of agents, divided into sub-classes:
- Penicillins,
- Cephalosporins
- Monobactams
- Carbapenems
How do beta-lactams work?
Beta-lactams have a ring that is structurally similar to acyl-D-alanyl-D alanine (precursor found in peptidoglycan layer).
The precursor is required for normal cell wall synthesis by transpeptidase enzyme (PBP = Penicillin binding protein).
B-lactam binds to the enzyme (PBP), inhibiting cell wall synthesis resulting in death due to osmotic instability.
What are glycopeptides?
Glycopeptides are antimicrobials that work on inhibiting the cell wall synthesis, such as
i) Vancomycin
ii) Teichoplanin
Narrow spectrum and a bit toxic.
How do glycopeptides work?
Glycopeptides:
- Large molecule binds to the end of the peptidoglycan.
- Bacterial enzymes (transpeptidase) are unable to incorporate precursor molecules to the wall.
Due to its size, it cannot cross the outer membrane of GN => active only against GPs.
What antimicrobials target cell membrane function and how do they do it?
Polymyxin and colistin.
Cyclic polypeptide agents that disrupt cell membrane function.
Increases permeability by interacting with phospholipids –> cell dies.
Can be toxic to host cells.
What antimicrobial groups target protein synthesis as a mode of action to inhibit?
Antimicrobials that inhibit and stop protein synthesis are:
- Aminoglycosides - blocks the initiation of translation and causes the misreading of mRNA
- Macrolide-Lincosamide-Streptogramin (MLS) Group - prevents the continuation of protein synthesis
- Oxazolidinones (Linezolid): MRSA/VRE - thought to interfere with the initiation of protein synthesis
- Chloramphenicol (toxic!) - prevents peptide bonds from being formed
- Tetracyclines (broad and -static) - blocks the attachment of tRNA to the ribosome
- Glycylglycines (Tigecyclin) (broad, IV)
How does Fluoroquinolones, Rifampin, and Metronidazole work as antimicrobials?
Fluoroquinolones, Rifampin, and Metronidazole:
Inhibit nuclei acid synthesis.
Fluoroquinolones is -cidal and broad - inhibits enzymes gyrase or topoisomerase so DNA is not replicated.
Rifampin inhibits production of RNA, big molecule (not for GN) better in combination with another antimicrobial.
Metronidazole is better in ANO2 environments, so good for ANO2 and capnophilic and protozoa.
Name two examples of Fluoroquinolones?
Fluoroquinolones:
- Ciprofloxacin
- Levofloxacin (not in < 18 y/o)
How do Sulfonamides and Trimethoprim work as a antimicrobial?
Sulfonamides –> Binds to dihydropteroate synthase and disrupts folic acid pathway.
Trimethoprim –> Binds to dihydrofolate reductase and disrupts folic acid pathway.
What is SXT?
SXT is a combination of Sulfamethoxazole and trimethoprim together.
They work in synergy and overall are of low toxicity. Both disrupt the production of folic acid.
What does Nitrofurantoin do as an antimicrobial?
Nitrofurantoin has several targets to inhibit on bacteria. It is a broad spectrum antimicrobial only for UTI’s.
What is biological and clinical resistance (separately)?
Biological Resistance = alteration of structure or physiology that results in reduced susceptibility.
Clinical Resistance = alteration of structure or physiology that makes the drug not be effective any longer, clinically.
What is environmental resistance?
Alteration in the environment due to chemical or physical characteristics (pH, atmosphere, cations, thymidine) that cause resistance.
What is it called when the organism is resistance naturally based on their original genetic information?
Microorganism mediated resistance.
